<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/NCT03765762</url>
  </required_header>
  <id_info>
    <org_study_id>Alkahest study 6019-202</org_study_id>
    <nct_id>NCT03765762</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of Pulsed GRF6019 Infusions in Subjects With Severe Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alkahest, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alkahest, Inc.</source>
  <oversight_info>
    <has_dmc>No</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 study will evaluate the safety, tolerability, and potential cognitive benefit of the&#xD;
      experimental treatment GRF6019 in subjects with severe Alzheimer's disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled study to assess the safety,&#xD;
      tolerability and potential cognitive benefit of GRF6019, a human plasma protein fraction.&#xD;
      GRF6019 or placebo will be administered intravenously to subjects with severe Alzheimer's&#xD;
      disease every day for 5 consecutive days. The total study duration for each subject is&#xD;
      approximately 9 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Actual">December 17, 2019</completion_date>
  <primary_completion_date type="Actual">December 17, 2019</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of Treatment-emergent Adverse Events (Safety)</measure>
    <time_frame>5 weeks</time_frame>
    <description>Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability of GRF6019</measure>
    <time_frame>5 weeks</time_frame>
    <description>Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Mini-Mental State Examination (MMSE) Score</measure>
    <time_frame>Baseline and 5 weeks</time_frame>
    <description>Mean change from Baseline to 5 Weeks in the Mini-Mental State Examination (MMSE) score. The MMSE consists of 5 components: orientation to time and place, registration of 3 words, attention and calculation, recall of 3 words, and language. The scores from the 5 components are summed to obtain the overall MMSE total score. The MMSE total score can range from 0 to 30, with higher scores indicating better mental status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Impairment Battery (SIB) Total Score</measure>
    <time_frame>Baseline and 5 weeks</time_frame>
    <description>Mean change from baseline in the SIB total score. The SIB assesses cognition; test questions measure orientation, attention, language, praxis, visuospatial perception, construction, memory, orientation to name, and social interaction. There are 57 items and the range of possible scores is 0-133. Lower scores indicate greater cognitive impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)</measure>
    <time_frame>Baseline and 5 weeks</time_frame>
    <description>Mean change from baseline in the ADCS-ADL-Severe score. The ADCS-ADL-Severe contains 19 items covering physical and mental functioning and independence in self-care and assesses the competence in performing basic activities of daily living. The scores range from 0 to 54, with higher scores indicating less functional impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)</measure>
    <time_frame>Baseline and 5 weeks</time_frame>
    <description>Mean ADCS-CGIC score. A CGIC score is based on clinicians' observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. The ADCS-CGIC is a rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the subject and informant to make a global impression of change. After completing the interviews, the clinician records the clinical impression of change on a 7-point Likert-type scale (from marked improvement to marked worsening). A score of 4 indicates no change, while scores &gt; 4 indicate worsening and scores &lt; 4 indicate improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score</measure>
    <time_frame>Baseline and 5 weeks</time_frame>
    <description>Mean change from Baseline to 5 weeks in the NPI-NH total score. The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains (Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor Behavior, Sleep and Nighttime Behavior Disorders, Appetite/Eating Changes). For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), with a possible summed total score of 0 to 144. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychiatric Inventory (NPI) Caregiver Total Score</measure>
    <time_frame>Baseline and 5 weeks</time_frame>
    <description>Mean change from Baseline to 5 Weeks in NPI Total Score. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains (Delusions, Hallucinations, Agitation/Aggression, Dysphoria/Depression, Anxiety, Euphoria/Elation, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor, Nighttime Behavior, Appetite/Eating). For each of the 12 behavioral domains the Distress (scale:0=Not distressing at all to 5=Extreme) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (distress x severity), with a possible summed total score of 0 to 180. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Severe Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>GRF6019</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GRF6019</intervention_name>
    <description>GRF6019 for IV infusion</description>
    <arm_group_label>GRF6019</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo for IV infusion</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of probable AD according to the National Institute on Aging-Alzheimer's&#xD;
             Association (NIA-AA) Criteria&#xD;
&#xD;
          -  MMSE Score 0-10 inclusive&#xD;
&#xD;
          -  Modified Hachinski Ischemia Scale (MHIS) score of 4 or less&#xD;
&#xD;
          -  Provided a signed and dated informed consent form (either the subject and/or subject's&#xD;
             legal representative)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of clinically relevant neurological disorder(s) other than probable AD&#xD;
&#xD;
          -  History of blood coagulation disorders or hypercoagulability; any concurrent use of an&#xD;
             anticoagulant therapy. (e.g., heparin, warfarin, thrombin inhibitors, Factor Xa&#xD;
             inhibitors). Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is acceptable.&#xD;
&#xD;
          -  Unstable coronary heart disease, e.g. myocardial infarction or severe or unstable&#xD;
             angina in the 6 months prior to dosing.&#xD;
&#xD;
          -  Moderate to severe congestive heart failure (New York Association Class III or IV).&#xD;
&#xD;
          -  Poorly controlled high blood pressure (systolic blood pressure of 160 mmHg or higher&#xD;
             and/or diastolic blood pressure of 100 mmHg or higher) despite treatment during the 3&#xD;
             months prior to dosing, or treatment refractory high blood pressure, defined as&#xD;
             treatment requiring 3 or more antihypertensives from different classes.&#xD;
&#xD;
          -  Prior hypersensitivity reaction to any human blood product or intravenous infusion;&#xD;
             any known clinically significant drug allergy.&#xD;
&#xD;
          -  Treatment with any human blood product, including transfusions and intravenous&#xD;
             immunoglobulin, during the 6 months prior to screening.&#xD;
&#xD;
          -  History of immunoglobulin A (IgA), haptoglobulin or C1 inhibitor deficiency; stroke,&#xD;
             anaphylaxis, or thromboembolic complications of intravenous immunoglobulins.&#xD;
&#xD;
          -  Hemoglobin &lt;10 g/dL in women; and &lt;11 g/dL in men.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alkahest Program Physician</last_name>
    <role>Study Director</role>
    <affiliation>Alkahest, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cognitive Clinical Trials</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85297</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognitive Clinical Trials</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognitive Clinical Trials</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Network</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riverside Clinical Research</name>
      <address>
        <city>Edgewater</city>
        <state>Florida</state>
        <zip>32132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bio Behavioral Health</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <results_first_submitted>December 11, 2020</results_first_submitted>
  <results_first_submitted_qc>January 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 27, 2021</results_first_posted>
  <last_update_submitted>January 8, 2021</last_update_submitted>
  <last_update_submitted_qc>January 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brain Diseases</keyword>
  <keyword>Nervous System Diseases</keyword>
  <keyword>Central Nervous System Diseases</keyword>
  <keyword>Neurodegenerative Diseases</keyword>
  <keyword>Neurocognitive Disorders</keyword>
  <keyword>Mental Disorders</keyword>
  <keyword>Dementia</keyword>
  <keyword>Tauopathy</keyword>
  <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>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 10, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03765762/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03765762/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>GRF6019</title>
          <description>GRF6019 250 mL IV for 5 consecutive days</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo 250 mL IV for 5 consecutive days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>GRF6019</title>
          <description>GRF6019 250 mL IV for 5 consecutive days</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo 250 mL IV for 5 consecutive days</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="18"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="26"/>
          </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="75.2" spread="8.25"/>
                    <measurement group_id="B2" value="69.5" spread="8.12"/>
                    <measurement group_id="B3" value="73.5" spread="8.49"/>
                  </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="11"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="25"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of Alzheimer's Disease</title>
          <description>Years of Alzheimer's Disease Duration calculated from Medical History Year of Diagnosis to Year of Informed Consent</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.0" spread="1.81"/>
                    <measurement group_id="B2" value="6.0" spread="3.59"/>
                    <measurement group_id="B3" value="5.3" spread="2.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Frequency of Treatment-emergent Adverse Events (Safety)</title>
        <description>Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class</description>
        <time_frame>5 weeks</time_frame>
        <population>Safety: All subjects who received any amount of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Treatment-emergent Adverse Events (Safety)</title>
          <description>Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class</description>
          <population>Safety: All subjects who received any amount of study treatment</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="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tolerability of GRF6019</title>
        <description>Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions</description>
        <time_frame>5 weeks</time_frame>
        <population>Safety: All subjects who received any amount of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Tolerability of GRF6019</title>
          <description>Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions</description>
          <population>Safety: All subjects who received any amount of study treatment</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="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Mini-Mental State Examination (MMSE) Score</title>
        <description>Mean change from Baseline to 5 Weeks in the Mini-Mental State Examination (MMSE) score. The MMSE consists of 5 components: orientation to time and place, registration of 3 words, attention and calculation, recall of 3 words, and language. The scores from the 5 components are summed to obtain the overall MMSE total score. The MMSE total score can range from 0 to 30, with higher scores indicating better mental status.</description>
        <time_frame>Baseline and 5 weeks</time_frame>
        <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>The Mini-Mental State Examination (MMSE) Score</title>
          <description>Mean change from Baseline to 5 Weeks in the Mini-Mental State Examination (MMSE) score. The MMSE consists of 5 components: orientation to time and place, registration of 3 words, attention and calculation, recall of 3 words, and language. The scores from the 5 components are summed to obtain the overall MMSE total score. The MMSE total score can range from 0 to 30, with higher scores indicating better mental status.</description>
          <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="3.53"/>
                    <measurement group_id="O2" value="1.8" spread="3.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Impairment Battery (SIB) Total Score</title>
        <description>Mean change from baseline in the SIB total score. The SIB assesses cognition; test questions measure orientation, attention, language, praxis, visuospatial perception, construction, memory, orientation to name, and social interaction. There are 57 items and the range of possible scores is 0-133. Lower scores indicate greater cognitive impairment.</description>
        <time_frame>Baseline and 5 weeks</time_frame>
        <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Impairment Battery (SIB) Total Score</title>
          <description>Mean change from baseline in the SIB total score. The SIB assesses cognition; test questions measure orientation, attention, language, praxis, visuospatial perception, construction, memory, orientation to name, and social interaction. There are 57 items and the range of possible scores is 0-133. Lower scores indicate greater cognitive impairment.</description>
          <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="7.59"/>
                    <measurement group_id="O2" value="10.4" spread="4.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)</title>
        <description>Mean change from baseline in the ADCS-ADL-Severe score. The ADCS-ADL-Severe contains 19 items covering physical and mental functioning and independence in self-care and assesses the competence in performing basic activities of daily living. The scores range from 0 to 54, with higher scores indicating less functional impairment.</description>
        <time_frame>Baseline and 5 weeks</time_frame>
        <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)</title>
          <description>Mean change from baseline in the ADCS-ADL-Severe score. The ADCS-ADL-Severe contains 19 items covering physical and mental functioning and independence in self-care and assesses the competence in performing basic activities of daily living. The scores range from 0 to 54, with higher scores indicating less functional impairment.</description>
          <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="5.05"/>
                    <measurement group_id="O2" value="0.5" spread="4.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)</title>
        <description>Mean ADCS-CGIC score. A CGIC score is based on clinicians' observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. The ADCS-CGIC is a rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the subject and informant to make a global impression of change. After completing the interviews, the clinician records the clinical impression of change on a 7-point Likert-type scale (from marked improvement to marked worsening). A score of 4 indicates no change, while scores &gt; 4 indicate worsening and scores &lt; 4 indicate improvement.</description>
        <time_frame>Baseline and 5 weeks</time_frame>
        <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)</title>
          <description>Mean ADCS-CGIC score. A CGIC score is based on clinicians' observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. The ADCS-CGIC is a rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the subject and informant to make a global impression of change. After completing the interviews, the clinician records the clinical impression of change on a 7-point Likert-type scale (from marked improvement to marked worsening). A score of 4 indicates no change, while scores &gt; 4 indicate worsening and scores &lt; 4 indicate improvement.</description>
          <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" spread="0.83"/>
                    <measurement group_id="O2" value="4.0" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score</title>
        <description>Mean change from Baseline to 5 weeks in the NPI-NH total score. The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains (Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor Behavior, Sleep and Nighttime Behavior Disorders, Appetite/Eating Changes). For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), with a possible summed total score of 0 to 144. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.</description>
        <time_frame>Baseline and 5 weeks</time_frame>
        <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score</title>
          <description>Mean change from Baseline to 5 weeks in the NPI-NH total score. The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains (Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor Behavior, Sleep and Nighttime Behavior Disorders, Appetite/Eating Changes). For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), with a possible summed total score of 0 to 144. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.</description>
          <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.0" spread="19.16"/>
                    <measurement group_id="O2" value="-20.0" spread="5.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neuropsychiatric Inventory (NPI) Caregiver Total Score</title>
        <description>Mean change from Baseline to 5 Weeks in NPI Total Score. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains (Delusions, Hallucinations, Agitation/Aggression, Dysphoria/Depression, Anxiety, Euphoria/Elation, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor, Nighttime Behavior, Appetite/Eating). For each of the 12 behavioral domains the Distress (scale:0=Not distressing at all to 5=Extreme) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (distress x severity), with a possible summed total score of 0 to 180. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.</description>
        <time_frame>Baseline and 5 weeks</time_frame>
        <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
        <group_list>
          <group group_id="O1">
            <title>GRF6019</title>
            <description>GRF6019 250 mL IV for 5 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 250 mL IV for 5 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Neuropsychiatric Inventory (NPI) Caregiver Total Score</title>
          <description>Mean change from Baseline to 5 Weeks in NPI Total Score. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains (Delusions, Hallucinations, Agitation/Aggression, Dysphoria/Depression, Anxiety, Euphoria/Elation, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor, Nighttime Behavior, Appetite/Eating). For each of the 12 behavioral domains the Distress (scale:0=Not distressing at all to 5=Extreme) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (distress x severity), with a possible summed total score of 0 to 180. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.</description>
          <population>Evaluable: Subjects who received at least 4 of the 5 planned infusions</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.7" spread="11.60"/>
                    <measurement group_id="O2" value="1.5" spread="4.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>5 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>GRF6019</title>
          <description>GRF6019 250 mL IV for 5 consecutive days</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo 250 mL IV for 5 consecutive days</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="8" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine phosphokinase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </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 Clinical Trial Agreement contains language that restricts the PI from discussing or publishing Sponsor confidential and/or proprietary information. The embargo period may be extended by mutual agreement of the Sponsor and PI.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Communications</name_or_title>
      <organization>Alkahest, Inc.</organization>
      <phone>(650) 801-0474</phone>
      <email>info@alkahest.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/NCT03765762
org study id: Alkahest study 6019-202
nct id: NCT03765762
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety, tolerability, and potential cognitive benefit of the
      experimental treatment GRF6019 in subjects with severe Alzheimer's disease.
This is a randomized, double-blind, placebo-controlled study to assess the safety,
      tolerability and potential cognitive benefit of GRF6019, a human plasma protein fraction.
      GRF6019 or placebo will be administered intravenously to subjects with severe Alzheimer's
      disease every day for 5 consecutive days. The total study duration for each subject is
      approximately 9 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Frequency of Treatment-emergent Adverse Events (Safety)
time frame: 5 weeks
description: Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class
measure: Tolerability of GRF6019
time frame: 5 weeks
description: Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
measure: The Mini-Mental State Examination (MMSE) Score
time frame: Baseline and 5 weeks
description: Mean change from Baseline to 5 Weeks in the Mini-Mental State Examination (MMSE) score. The MMSE consists of 5 components: orientation to time and place, registration of 3 words, attention and calculation, recall of 3 words, and language. The scores from the 5 components are summed to obtain the overall MMSE total score. The MMSE total score can range from 0 to 30, with higher scores indicating better mental status.
measure: Severe Impairment Battery (SIB) Total Score
time frame: Baseline and 5 weeks
description: Mean change from baseline in the SIB total score. The SIB assesses cognition; test questions measure orientation, attention, language, praxis, visuospatial perception, construction, memory, orientation to name, and social interaction. There are 57 items and the range of possible scores is 0-133. Lower scores indicate greater cognitive impairment.
measure: Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)
time frame: Baseline and 5 weeks
description: Mean change from baseline in the ADCS-ADL-Severe score. The ADCS-ADL-Severe contains 19 items covering physical and mental functioning and independence in self-care and assesses the competence in performing basic activities of daily living. The scores range from 0 to 54, with higher scores indicating less functional impairment.
measure: Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)
time frame: Baseline and 5 weeks
description: Mean ADCS-CGIC score. A CGIC score is based on clinicians' observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. The ADCS-CGIC is a rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the subject and informant to make a global impression of change. After completing the interviews, the clinician records the clinical impression of change on a 7-point Likert-type scale (from marked improvement to marked worsening). A score of 4 indicates no change, while scores > 4 indicate worsening and scores < 4 indicate improvement.
measure: Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score
time frame: Baseline and 5 weeks
description: Mean change from Baseline to 5 weeks in the NPI-NH total score. The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains (Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor Behavior, Sleep and Nighttime Behavior Disorders, Appetite/Eating Changes). For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), with a possible summed total score of 0 to 144. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.
measure: Neuropsychiatric Inventory (NPI) Caregiver Total Score
time frame: Baseline and 5 weeks
description: Mean change from Baseline to 5 Weeks in NPI Total Score. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains (Delusions, Hallucinations, Agitation/Aggression, Dysphoria/Depression, Anxiety, Euphoria/Elation, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor, Nighttime Behavior, Appetite/Eating). For each of the 12 behavioral domains the Distress (scale:0=Not distressing at all to 5=Extreme) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (distress x severity), with a possible summed total score of 0 to 180. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.
arm group label: GRF6019
arm group type: Experimental
description: Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days.
intervention type: Drug
intervention name: GRF6019
description: GRF6019 for IV infusion
arm group label: GRF6019
intervention type: Other
intervention name: Placebo
description: Placebo for IV infusion
arm group label: Placebo
other name: Normal Saline
criteria: 
gender: All
minimum age: 60 Years
maximum age: 95 Years
healthy volunteers: No
last name: Alkahest Program Physician
role: Study Director
affiliation: Alkahest, Inc.
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country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: No
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