<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03828747</url>
  </required_header>
  <id_info>
    <org_study_id>GN40040</org_study_id>
    <nct_id>NCT03828747</nct_id>
  </id_info>
  <brief_title>A Study of Semorinemab in Patients With Moderate Alzheimer's Disease</brief_title>
  <official_title>A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group&#xD;
      study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of&#xD;
      semorinemab in patients with moderate AD. The study consists of a screening period, a&#xD;
      double-blind treatment period, an optional open-label extension (OLE) period, and a safety&#xD;
      follow-up period. There may be up to two study cohorts.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 30, 2019</start_date>
  <completion_date type="Anticipated">August 23, 2023</completion_date>
  <primary_completion_date type="Actual">July 20, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events</measure>
    <time_frame>Baseline up to Clinical Cut Off Date (CCOD) of July 20, 2021 (approximately 2.5 years)</time_frame>
    <description>An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of RO7105705 at Specified Timepoints</measure>
    <time_frame>Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline</measure>
    <time_frame>Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Percentage of Participants With Adverse Events</measure>
    <time_frame>Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.</time_frame>
    <description>Descriptive statistics will be used for assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>Descriptive statistics will be used for assessment.&#xD;
A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>Descriptive statistics will be used for assessment.&#xD;
A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>Descriptive statistics will be used for assessment.&#xD;
A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)</measure>
    <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
    <description>Descriptive statistics will be used for assessment.&#xD;
The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints</measure>
    <time_frame>Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
    <description>Descriptive statistics will be used for assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline</measure>
    <time_frame>Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
    <description>Descriptive statistics will be used for assessment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">272</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Semorinemab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Semorinemab</intervention_name>
    <description>Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.</description>
    <arm_group_label>Semorinemab</arm_group_label>
    <other_name>MTAU9937A</other_name>
    <other_name>RO7105705</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[18F]GTP1</intervention_name>
    <description>[18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Semorinemab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  National Institute on Aging/Alzheimer's Association core clinical criteria for&#xD;
             probable AD dementia&#xD;
&#xD;
          -  Evidence of the AD pathological process, by a positive amyloid assessment either on&#xD;
             CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan&#xD;
&#xD;
          -  AD dementia of moderate severity, as defined by a screening MMSE score of 16-21&#xD;
             points, inclusive, and a CDR-GS of 1 or 2&#xD;
&#xD;
          -  Availability of a person with sufficient contact with the participant to be able to&#xD;
             provide accurate information on the participant's cognitive, behavioral and functional&#xD;
             ability&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Inability to tolerate MRI procedures or contraindication to MRI&#xD;
&#xD;
          -  Contraindication to PET imaging&#xD;
&#xD;
          -  Residence in a skilled nursing facility&#xD;
&#xD;
          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the&#xD;
             investigator's judgment, precludes the patient's safe participation in and completion&#xD;
             of the study, or bias the assessment of the clinical or mental status of the&#xD;
             participant to a significant degree&#xD;
&#xD;
          -  Any evidence of a condition other than AD that may affect cognition&#xD;
&#xD;
          -  Substance abuse within the past 2 years&#xD;
&#xD;
          -  Use of any experimental therapy within 90 days or 5 half-lives prior to screening,&#xD;
             whichever is greater, or any passive immunotherapy against tau&#xD;
&#xD;
          -  Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was&#xD;
             at least 1 year prior to screening or any active immunotherapy (vaccine) that is under&#xD;
             evaluation to prevent or postpone cognitive decline&#xD;
&#xD;
          -  Any other biologic therapy or previous treatment with medications specifically&#xD;
             intended to treat Parkinsonian symptoms or any other non-AD neurodegenerative disorder&#xD;
             within 1 year of screening&#xD;
&#xD;
          -  Systemic immunosuppressive therapy within 12 months of screening through the entire&#xD;
             study period&#xD;
&#xD;
          -  Typical antipsychotic or neuroleptic medication within 6 months of screening&#xD;
&#xD;
          -  Daily treatment with any of the following classes of medication (except for&#xD;
             intermittent short-term use): opiates or opioids, benzodiazepines, barbiturates,&#xD;
             hypnotics, or any medication with clinically significant centrally-acting&#xD;
             antihistamine or anticholinergic activity&#xD;
&#xD;
          -  Stimulant medications, unless the dose has been stable within the 6 months prior to&#xD;
             screening and is expected to be stable throughout the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, Inc.</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pharmacology Research Institute</name>
      <address>
        <city>Los Alamitos</city>
        <state>California</state>
        <zip>90720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University; Stanford Clinical Cancer Ctr</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Network - PRN</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Molecular Neuroimaging; MRI/PET</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KI Health Partners, LLC; New England Institute for Clinical Research</name>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <zip>06905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JEM Research LLC</name>
      <address>
        <city>Atlantis</city>
        <state>Florida</state>
        <zip>33462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bradenton Research Center</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Matters Research, Inc.</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33445</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuropsychiatric Research; Center of Southwest Florida</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Jewish Health Systems</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33137</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collier Neurologic Specialists</name>
      <address>
        <city>Naples</city>
        <state>Florida</state>
        <zip>34105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research US, Inc. - Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimer's Research and Treatment Center</name>
      <address>
        <city>Wellington</city>
        <state>Florida</state>
        <zip>33414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premiere Research Institute</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center - Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Neuroscience Institute</name>
      <address>
        <city>Elk Grove Village</city>
        <state>Illinois</state>
        <zip>60007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Illinois University, School of Medicine</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Womens Hospital; Center for Alzheimer Research &amp; Treatment</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimers Disease Center</name>
      <address>
        <city>Quincy</city>
        <state>Massachusetts</state>
        <zip>02169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Memory and Aging</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Memory Research Institute of NJ</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Empire Neurology PC; MS Center of Northeastern NY</name>
      <address>
        <city>Latham</city>
        <state>New York</state>
        <zip>12110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester; AD-CARE</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Research Network Inc.</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abington Neurological Associates</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Mood &amp; Memory Research Institute</name>
      <address>
        <city>East Providence</city>
        <state>Rhode Island</state>
        <zip>02914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Butler Hospital; Movement Disorders Program</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02906</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Clinic PC</name>
      <address>
        <city>Cordova</city>
        <state>Tennessee</state>
        <zip>38018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Orleans Center for Clinical Research</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Memory Clinic</name>
      <address>
        <city>Bennington</city>
        <state>Vermont</state>
        <zip>05201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Toulouse</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de la Timone - Hopital d Adultes; Service de Neurologie</name>
      <address>
        <city>Marseille</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitie-Salpetriere</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Rennes - Hopital Pontchaillou</name>
      <address>
        <city>Rennes cedex 09</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital des Charpennes</name>
      <address>
        <city>Villeurbanne</city>
        <zip>69100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Podlaskie Centrum Psychogeriatrii</name>
      <address>
        <city>Białystok</city>
        <zip>15-756</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo-Med Zielinski i wspolnicy Sp. j.</name>
      <address>
        <city>Katowice</city>
        <zip>40-650</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek</name>
      <address>
        <city>Poznań</city>
        <zip>61-853</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osrodek Badan Klinicznych Euromedis</name>
      <address>
        <city>Szczecin</city>
        <zip>70-111</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne NeuroProtect</name>
      <address>
        <city>Warszawa</city>
        <zip>01-684</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne AMED</name>
      <address>
        <city>Warszawa</city>
        <zip>03-291</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ WCA</name>
      <address>
        <city>Wrocław</city>
        <zip>53-659</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Mutua de Terrassa</name>
      <address>
        <city>Terrassa</city>
        <state>Barcelona</state>
        <zip>08221</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacio ACE</name>
      <address>
        <city>Barcelona</city>
        <zip>08028</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic I Provincial</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Doctor Peset</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <results_first_submitted>July 15, 2022</results_first_submitted>
  <results_first_submitted_qc>September 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">October 3, 2022</results_first_posted>
  <last_update_submitted>September 1, 2022</last_update_submitted>
  <last_update_submitted_qc>September 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 14, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03828747/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 49 centers in 4 countries.</recruitment_details>
      <pre_assignment_details>A total of 272 participants were enrolled at 49 centers. 5 participants did not receive blinded treatment. These 267 participants represented the Safety Analysis population and data for this population is presented here.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Semorinemab</title>
          <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-Blind Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="135"/>
                <participants group_id="P2" count="132"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Cohort 1</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Cohort 2</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="46"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="104"/>
                <participants group_id="P2" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Various reasons</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open-Label Extension</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="104"/>
                <participants group_id="P2" count="95"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="104"/>
                <participants group_id="P2" count="95"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Continuing on Study</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
                <participants group_id="P2" count="72"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Various reasons</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Semorinemab</title>
          <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="135"/>
            <count group_id="B2" value="132"/>
            <count group_id="B3" value="267"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71.6" spread="8.2"/>
                    <measurement group_id="B2" value="73.1" spread="8.0"/>
                    <measurement group_id="B3" value="72.3" spread="8.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="80"/>
                    <measurement group_id="B3" value="173"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="116"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="227"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="121"/>
                    <measurement group_id="B2" value="115"/>
                    <measurement group_id="B3" value="236"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)</title>
        <description>The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 score.</population>
        <group_list>
          <group group_id="O1">
            <title>Semorinemab</title>
            <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)</title>
          <description>The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.</description>
          <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 score.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="115"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.93" spread="0.533"/>
                    <measurement group_id="O2" value="24.09" spread="0.589"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 49 (includes Cohort 1 and 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.96" spread="0.658"/>
                    <measurement group_id="O2" value="6.85" spread="0.643"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 61 (only Cohort 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                    <count group_id="O2" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.71" spread="0.907"/>
                    <measurement group_id="O2" value="8.47" spread="0.965"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 49</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0008</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-2.89</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.849</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.56</ci_lower_limit>
            <ci_upper_limit>-1.21</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 61</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0351</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-2.75</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.287</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.31</ci_lower_limit>
            <ci_upper_limit>-0.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)</title>
        <description>The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the ADCS-ADL score at the given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Semorinemab</title>
            <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)</title>
          <description>The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.</description>
          <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the ADCS-ADL score at the given time point.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="115"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.03" spread="0.764"/>
                    <measurement group_id="O2" value="59.74" spread="0.842"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 49 (includes Cohort 1 and 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.63" spread="1.002"/>
                    <measurement group_id="O2" value="-6.80" spread="0.974"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 61 (only Cohort 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.29" spread="1.343"/>
                    <measurement group_id="O2" value="-7.57" spread="1.462"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 49</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5207</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.83</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.295</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-3.39</ci_lower_limit>
            <ci_upper_limit>1.72</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 61</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3704</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.72</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.911</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-5.50</ci_lower_limit>
            <ci_upper_limit>2.07</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)</title>
        <description>The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the CDR-SB score at the given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Semorinemab</title>
            <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)</title>
          <description>The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.</description>
          <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the CDR-SB score at the given time point.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="115"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.23" spread="0.156"/>
                    <measurement group_id="O2" value="6.51" spread="0.182"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 49 (includes Cohort 1 and 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="109"/>
                    <count group_id="O2" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.80" spread="0.217"/>
                    <measurement group_id="O2" value="1.54" spread="0.214"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 61 (only Cohort 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.45" spread="0.367"/>
                    <measurement group_id="O2" value="2.28" spread="0.393"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 49</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3501</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>0.26</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.282</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.29</ci_lower_limit>
            <ci_upper_limit>0.82</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 61</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7431</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>0.17</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.525</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.87</ci_lower_limit>
            <ci_upper_limit>1.22</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)</title>
        <description>The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the MMSE score at the given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Semorinemab</title>
            <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)</title>
          <description>The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.</description>
          <population>The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 and the MMSE score at the given time point.</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="115"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.38" spread="0.182"/>
                    <measurement group_id="O2" value="18.15" spread="0.197"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 49 (includes Cohort 1 and 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.86" spread="0.330"/>
                    <measurement group_id="O2" value="-3.12" spread="0.325"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 61 (only Cohort 2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.14" spread="0.429"/>
                    <measurement group_id="O2" value="-4.22" spread="0.466"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 49</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5366</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>0.27</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.429</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.58</ci_lower_limit>
            <ci_upper_limit>1.11</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline at Week 61</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0851</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>1.08</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.618</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.15</ci_lower_limit>
            <ci_upper_limit>2.30</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events</title>
        <description>An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
        <time_frame>Baseline up to Clinical Cut Off Date (CCOD) of July 20, 2021 (approximately 2.5 years)</time_frame>
        <population>The safety population included all randomized participants who received at least one dose of either semorinemab or placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Semorinemab</title>
            <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events</title>
          <description>An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
          <population>The safety population included all randomized participants who received at least one dose of either semorinemab or placebo.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="135"/>
                <count group_id="O2" value="132"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113"/>
                    <measurement group_id="O2" value="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Concentration of RO7105705 at Specified Timepoints</title>
        <time_frame>Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline</title>
        <time_frame>Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Percentage of Participants With Adverse Events</title>
        <description>Descriptive statistics will be used for assessment.</description>
        <time_frame>Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)</title>
        <description>Descriptive statistics will be used for assessment.&#xD;
A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)</title>
        <description>Descriptive statistics will be used for assessment.&#xD;
A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)</title>
        <description>Descriptive statistics will be used for assessment.&#xD;
A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)</title>
        <description>Descriptive statistics will be used for assessment.&#xD;
The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.</description>
        <time_frame>Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints</title>
        <description>Descriptive statistics will be used for assessment.</description>
        <time_frame>Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline</title>
        <description>Descriptive statistics will be used for assessment.</description>
        <time_frame>Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.</time_frame>
        <posting_date>08/2024</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to CCOD of July 20, 2021 (approximately 2.5 years)</time_frame>
      <desc>The safety population included all randomized participants who received at least one dose of either semorinemab or placebo.</desc>
      <group_list>
        <group group_id="E1">
          <title>Semorinemab (Double Blind)</title>
          <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.</description>
        </group>
        <group group_id="E3">
          <title>Semorinemab (OLE)</title>
          <description>Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="132"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="132"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Stress cardiomyopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Hernial eventration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Inguinal hernia strangulated</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Chronic Exacerbated Cholecystitis on the Background of Urolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Joint dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Patella fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>SARS-CoV-2 test positive</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Diabetic metabolic decompensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma metastatic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Invasive ductal breast carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Ovarian cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Renal neoplasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Transitional cell carcinoma recurrent</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Bladder cancer recurrent</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Upper motor neurone lesion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="132"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Peripheral artery thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Peripheral artery aneurysm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="77" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="71" subjects_at_risk="132"/>
                <counts group_id="E3" subjects_affected="52" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="135"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="132"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="135"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="135"/>
                <counts group_id="E2" events="19" subjects_affected="16" subjects_at_risk="132"/>
                <counts group_id="E3" events="11" subjects_affected="10" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="19" subjects_affected="14" subjects_at_risk="135"/>
                <counts group_id="E2" events="28" subjects_affected="19" subjects_at_risk="132"/>
                <counts group_id="E3" events="16" subjects_affected="9" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="30" subjects_affected="14" subjects_at_risk="135"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="132"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="135"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="132"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="135"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="132"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="14" subjects_affected="11" subjects_at_risk="135"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="132"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="135"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="132"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="135"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="132"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="135"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="132"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="194"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="132"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="135"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="132"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="194"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800-821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03828747
org study id: GN40040
nct id: NCT03828747
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group
      study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of
      semorinemab in patients with moderate AD. The study consists of a screening period, a
      double-blind treatment period, an optional open-label extension (OLE) period, and a safety
      follow-up period. There may be up to two study cohorts.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.
measure: Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.
measure: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.
measure: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.
measure: Percentage of Participants With Adverse Events
time frame: Baseline up to Clinical Cut Off Date (CCOD) of July 20, 2021 (approximately 2.5 years)
description: An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
measure: Serum Concentration of RO7105705 at Specified Timepoints
time frame: Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
measure: Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
time frame: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
measure: Relationship Between ADA Status and Percentage of Participants With Adverse Events
time frame: Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.
description: Descriptive statistics will be used for assessment.
measure: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: Descriptive statistics will be used for assessment.
A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.
measure: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: Descriptive statistics will be used for assessment.
A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.
measure: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: Descriptive statistics will be used for assessment.
A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.
measure: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
description: Descriptive statistics will be used for assessment.
The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.
measure: Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints
time frame: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
description: Descriptive statistics will be used for assessment.
measure: Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
time frame: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
description: Descriptive statistics will be used for assessment.
arm group label: Semorinemab
arm group type: Experimental
description: Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
intervention type: Drug
intervention name: Semorinemab
description: Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.
arm group label: Semorinemab
other name: MTAU9937A
other name: RO7105705
intervention type: Drug
intervention name: Placebo
description: Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.
arm group label: Placebo
intervention type: Drug
intervention name: [18F]GTP1
description: [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
arm group label: Placebo
arm group label: Semorinemab
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: France
country: Poland
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 