<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/NCT01677572</url>
  </required_header>
  <id_info>
    <org_study_id>221AD103</org_study_id>
    <secondary_id>2012-000349-10</secondary_id>
    <nct_id>NCT01677572</nct_id>
  </id_info>
  <brief_title>Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease</brief_title>
  <acronym>PRIME</acronym>
  <official_title>A Randomized, Double-Blinded, Placebo-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB037 in Subjects With Prodromal or Mild Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biogen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the safety and tolerability of multiple&#xD;
      doses of Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) in participants with&#xD;
      prodromal or mild Alzheimer's Disease (AD). The secondary objectives of this study are to&#xD;
      assess the effect on cerebral amyloid plaque content as measured by florbetapir-fluorine-18&#xD;
      (18F-AV-45F-AV-45) positron emission tomography (PET) imaging, to assess the multiple dose&#xD;
      serum concentrations of Aducanumab and to evaluate the immunogenicity of Aducanumab after&#xD;
      multiple dose administration in this population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study consists of a placebo-controlled period to study week 54, followed by a long-term&#xD;
      extension to study week 518. The placebo-controlled period is conducted with a staggered,&#xD;
      parallel group design, with the first 3 treatment arms conducted in parallel, 2 further&#xD;
      treatment arms subsequently beginning in parallel, 2 additional treatment arms beginning in&#xD;
      parallel, and the last 2 treatment arms subsequently beginning in parallel. Qualifying&#xD;
      participants can enter the long-term extension period for up to 42 additional doses of active&#xD;
      drug for the first 3 years of LTE. Furthermore, up until the last participant in Arms 8 and 9&#xD;
      has had his or her last dose in the fifth year of the LTE, eligible participants will be able&#xD;
      to continue treatment beyond the third year of the LTE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and&#xD;
    NCT02484547) and not based on safety concerns.&#xD;
  </why_stopped>
  <start_date type="Actual">October 5, 2012</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 31, 2019</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events</measure>
    <time_frame>Baseline to week 518</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.</measure>
    <time_frame>Day 1, Weeks 26, 54, End of year 2, 3, and 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab</measure>
    <time_frame>Up to week 518</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.</measure>
    <time_frame>Up to week 518</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">197</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Low-dose #1 Aducanumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous doses of low-dose level #1 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-dose #2 Aducanumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous doses of low-dose level #2 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (low dose group)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mid-dose Aducanumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous doses of mid-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (mid dose group)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-dose Aducanumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous doses of high-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (high dose group)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aducanumab Titration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous doses of Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Titration Group)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)</intervention_name>
    <description>Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for up to an additional 112 doses.</description>
    <arm_group_label>Aducanumab Titration</arm_group_label>
    <arm_group_label>High-dose Aducanumab</arm_group_label>
    <arm_group_label>Low-dose #1 Aducanumab</arm_group_label>
    <arm_group_label>Low-dose #2 Aducanumab</arm_group_label>
    <arm_group_label>Mid-dose Aducanumab</arm_group_label>
    <arm_group_label>Placebo (high dose group)</arm_group_label>
    <arm_group_label>Placebo (low dose group)</arm_group_label>
    <arm_group_label>Placebo (mid dose group)</arm_group_label>
    <other_name>IgG1</other_name>
    <other_name>anti-A* mAb</other_name>
    <other_name>Fully human</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo to mimic the low dose, mid-dose and high-dose treatment arms of the experimental intervention; administered by intravenous (IV) infusion on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for up to an additional 112 doses.</description>
    <arm_group_label>Placebo (Titration Group)</arm_group_label>
    <arm_group_label>Placebo (high dose group)</arm_group_label>
    <arm_group_label>Placebo (low dose group)</arm_group_label>
    <arm_group_label>Placebo (mid dose group)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be ambulatory.&#xD;
&#xD;
          -  Participants must meet the following core clinical criteria as determined by the&#xD;
             Investigator:&#xD;
&#xD;
        Prodromal Alzheimer's Disease (AD) (all of the criteria must apply):&#xD;
&#xD;
          -  Mini Mental State Examination (MMSE) scores between 24-30 (inclusive)&#xD;
&#xD;
          -  a spontaneous memory complaint&#xD;
&#xD;
          -  objective memory loss defined as a free recall score of ≤27 on the Free and Cued&#xD;
             Selective Reminding Test (FCSRT)&#xD;
&#xD;
          -  a global Clinical Dementia Rating Scale (CDR) score of 0.5&#xD;
&#xD;
          -  absence of significant levels of impairment in other cognitive domains&#xD;
&#xD;
          -  essentially preserved activities of daily living, and an absence of dementia. OR&#xD;
&#xD;
        Mild Alzheimer's Disease (AD) criteria (all criteria must apply):&#xD;
&#xD;
          -  Mini Mental State Examination (MMSE) scores between 20-26 (inclusive)&#xD;
&#xD;
          -  a global Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0&#xD;
&#xD;
          -  meeting the National Institute on Aging-Alzheimer's Association core clinical criteria&#xD;
             for probable AD.&#xD;
&#xD;
          -  Participants must have a positive florbetapir positron emission tomography (PET)&#xD;
             amyloid scan.&#xD;
&#xD;
          -  Participants must consent to apolipoprotein E (ApoE) genotyping.&#xD;
&#xD;
          -  Apart from clinical diagnosis of Alzheimer's Disease (AD), participant must be in good&#xD;
             health.&#xD;
&#xD;
          -  Must have a reliable informant or caregiver.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Any medical or neurological condition (other than Alzheimer's Disease) that might be a&#xD;
             contributing cause of the participant's cognitive impairment.&#xD;
&#xD;
          -  Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of&#xD;
             consciousness in the past 1 year.&#xD;
&#xD;
          -  Clinically significant psychiatric illness in past 6 months.&#xD;
&#xD;
          -  Seizure in the past 3 years.&#xD;
&#xD;
          -  Poorly controlled diabetes mellitus.&#xD;
&#xD;
          -  History of unstable angina, myocardial infarction, chronic heart failure, or clinical&#xD;
             significant conduction abnormalities within 1 year prior to Screening.&#xD;
&#xD;
          -  Indication of impaired renal or liver function.&#xD;
&#xD;
          -  Have human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
          -  Have a significant systematic illness or infection in past 30 days.&#xD;
&#xD;
          -  Brain MRI showing evidence of acute or sub-acute micro or macrohemorrhage, greater&#xD;
             than 4 microhemorrhages, cortical infarct or greater than one 1 lunar infarct.&#xD;
&#xD;
          -  Any contraindications to brain MRI or positron emission tomography (PET) scans.&#xD;
&#xD;
          -  Negative positron emission tomography (PET) scan with any amyloid-targeting ligand&#xD;
             within 48 weeks of Screening.&#xD;
&#xD;
          -  Clinically significant 12-lead electrocardiogram (ECG) abnormalities.&#xD;
&#xD;
          -  Alcohol or substance abuse in past 1 year.&#xD;
&#xD;
          -  Taking blood thinners (except for aspirin at a prophylactic dose or less)&#xD;
&#xD;
          -  Have changes in medications or doses of medication in past 4 weeks.&#xD;
&#xD;
        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Biogen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NNS Clinical Research, LLC</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Senior Clinical Trials, Inc.</name>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Clinical Research Institute, Inc.</name>
      <address>
        <city>Lomita</city>
        <state>California</state>
        <zip>90717</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, LLC</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Neuroscience Medical Group</name>
      <address>
        <city>Oxnard</city>
        <state>California</state>
        <zip>93030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Network, Inc.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco Clinical Research Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimer's Disease Research Unit, Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20057</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>MD Clinical Trials, Inc.</name>
      <address>
        <city>Hallandale Beach</city>
        <state>Florida</state>
        <zip>33009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galiz Research, LLC</name>
      <address>
        <city>Miami Springs</city>
        <state>Florida</state>
        <zip>33166</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>Compass Research, LLC</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Infinity Clinical Research, Inc.</name>
      <address>
        <city>Sunrise</city>
        <state>Florida</state>
        <zip>33351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Axiom Clinical Research of Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stedman Clinical Trials, LLC</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurostudies.net, LLC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Neurosciences Institute</name>
      <address>
        <city>Elk Grove Village</city>
        <state>Illinois</state>
        <zip>60007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University School of Medicine</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Clinical Trials, LLC</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memory Enhancement Center of America, Inc.</name>
      <address>
        <city>Eatontown</city>
        <state>New Jersey</state>
        <zip>07724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRI Lifetree</name>
      <address>
        <city>Marlton</city>
        <state>New Jersey</state>
        <zip>08053</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</name>
      <address>
        <city>Latham</city>
        <state>New York</state>
        <zip>12110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Insight Clinical Trials LLC</name>
      <address>
        <city>Beachwood</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Research Network (Oregon) Inc.</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brown Hospital</name>
      <address>
        <city>East Providence</city>
        <state>Rhode Island</state>
        <zip>02906</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
    <country>Belgium</country>
  </removed_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>July 31, 2020</last_update_submitted>
  <last_update_submitted_qc>July 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aducanumab</keyword>
  <keyword>BIIB037</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulin G</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01677572
org study id: 221AD103
secondary id: 2012-000349-10
nct id: NCT01677572
lead sponsor: 
has dmc: Yes
The primary objective of this study is to evaluate the safety and tolerability of multiple
      doses of Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb) in participants with
      prodromal or mild Alzheimer's Disease (AD). The secondary objectives of this study are to
      assess the effect on cerebral amyloid plaque content as measured by florbetapir-fluorine-18
      (18F-AV-45F-AV-45) positron emission tomography (PET) imaging, to assess the multiple dose
      serum concentrations of Aducanumab and to evaluate the immunogenicity of Aducanumab after
      multiple dose administration in this population.
The study consists of a placebo-controlled period to study week 54, followed by a long-term
      extension to study week 518. The placebo-controlled period is conducted with a staggered,
      parallel group design, with the first 3 treatment arms conducted in parallel, 2 further
      treatment arms subsequently beginning in parallel, 2 additional treatment arms beginning in
      parallel, and the last 2 treatment arms subsequently beginning in parallel. Qualifying
      participants can enter the long-term extension period for up to 42 additional doses of active
      drug for the first 3 years of LTE. Furthermore, up until the last participant in Arms 8 and 9
      has had his or her last dose in the fifth year of the LTE, eligible participants will be able
      to continue treatment beyond the third year of the LTE.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Participants with Adverse Events
time frame: Baseline to week 518
measure: Change from baseline in florbetapir-fluorine-18 (18F-AV-45F-AV-45) positron emission tomography (PET) imaging in certain brain areas.
time frame: Day 1, Weeks 26, 54, End of year 2, 3, and 4
measure: Multiple dose pharmacokinetic (PK) serum concentrations of Aducanumab
time frame: Up to week 518
measure: Change from Baseline in Incidence of Anti-Aducanumab Antibodies in Serum.
time frame: Up to week 518
arm group label: Low-dose #1 Aducanumab
arm group type: Experimental
description: Intravenous doses of low-dose level #1 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Low-dose #2 Aducanumab
arm group type: Experimental
description: Intravenous doses of low-dose level #2 Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Placebo (low dose group)
arm group type: Placebo Comparator
description: Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Mid-dose Aducanumab
arm group type: Experimental
description: Intravenous doses of mid-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Placebo (mid dose group)
arm group type: Placebo Comparator
description: Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
arm group label: High-dose Aducanumab
arm group type: Experimental
description: Intravenous doses of high-dose Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Placebo (high dose group)
arm group type: Placebo Comparator
description: Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose administered approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Aducanumab Titration
arm group type: Experimental
description: Intravenous doses of Aducanumab administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
arm group label: Placebo (Titration Group)
arm group type: Placebo Comparator
description: Intravenous doses of placebo administered approximately 4 weeks apart over approximately 52 weeks (a total of 14 doses). Qualifying participants can continue into the long-term extension at a dose approximately 4 weeks apart for up to an additional 112 doses.
intervention type: Drug
intervention name: Aducanumab (recombinant, fully human anti-Aβ IgG1 mAb)
description: Participants will receive an infusion of Aducanumab on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic and assigned does levels. The infusion will be administered for approximately 1 hour. The study is conducted with a staggered, parallel group design, with the first 3 treatment arms conducted in parallel, 2 further treatment arms subsequently beginning in parallel and the 2 last treatment arms subsequently beginning in parallel. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for up to an additional 112 doses.
arm group label: Aducanumab Titration
arm group label: High-dose Aducanumab
arm group label: Low-dose #1 Aducanumab
arm group label: Low-dose #2 Aducanumab
arm group label: Mid-dose Aducanumab
arm group label: Placebo (high dose group)
arm group label: Placebo (low dose group)
arm group label: Placebo (mid dose group)
other name: IgG1
other name: anti-A* mAb
other name: Fully human
intervention type: Drug
intervention name: Placebo
description: Placebo to mimic the low dose, mid-dose and high-dose treatment arms of the experimental intervention; administered by intravenous (IV) infusion on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, and 365 (±2 days) at the study clinic. Qualifying participants can enter the long-term extension period at doses described in the treatment arms for up to an additional 112 doses.
arm group label: Placebo (Titration Group)
arm group label: Placebo (high dose group)
arm group label: Placebo (low dose group)
arm group label: Placebo (mid dose group)
criteria: 
gender: All
minimum age: 50 Years
maximum age: 90 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Biogen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
country: Australia
country: Belgium
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Immunoglobulin G