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A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT03765762
Recruitment Status : Completed
First Posted : December 5, 2018
Results First Posted : January 27, 2021
Last Update Posted : January 27, 2021
Sponsor:
Information provided by (Responsible Party):
Alkahest, Inc.

Tracking Information
First Submitted Date  ICMJE November 29, 2018
First Posted Date  ICMJE December 5, 2018
Results First Submitted Date  ICMJE December 11, 2020
Results First Posted Date  ICMJE January 27, 2021
Last Update Posted Date January 27, 2021
Actual Study Start Date  ICMJE January 15, 2019
Actual Primary Completion Date December 17, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2021)
  • Frequency of Treatment-emergent Adverse Events (Safety) [ Time Frame: 5 weeks ]
    Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class
  • Tolerability of GRF6019 [ Time Frame: 5 weeks ]
    Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2018)
  • Incidence of treatment-emergent adverse events (safety) [ Time Frame: Baseline to 5 weeks ]
    Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class
  • Tolerability of GRF6019 as assessed by number of patients completing the dosing regimen [ Time Frame: Baseline to 5 weeks ]
    Number of subjects completing 4 weeks after receiving 5 infusions
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2021)
  • The Mini-Mental State Examination (MMSE) Score [ Time Frame: Baseline and 5 weeks ]
    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.
  • Severe Impairment Battery (SIB) Total Score [ Time Frame: Baseline and 5 weeks ]
    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.
  • 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 ]
    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.
  • Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC) [ Time Frame: Baseline and 5 weeks ]
    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.
  • Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score [ Time Frame: Baseline and 5 weeks ]
    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.
  • Neuropsychiatric Inventory (NPI) Caregiver Total Score [ Time Frame: Baseline and 5 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2018)
  • The Mini-Mental State Examination (MMSE) Score [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the MMSE score. The MMSE is a 30-point questionnaire used to measure the extent of cognitive impairment. Lower scores indicate more severe cognitive impairment.
  • Severe Impairment Battery (SIB) [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the SIB 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.
  • Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe) [ Time Frame: Baseline to 5 weeks ]
    Changes 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.
  • Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC) [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the ADCS-CGIC score. A CGIC score is based on clinicians' observations of change in the patient'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 patient 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).
  • Neuropsychiatric Inventory Nursing Home (NPI-NH) Version [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the NPI-NH score. NPI-NH consists of 12 behavioral domains and is to assess psychiatric symptoms in patients with dementia in outpatient settings. For each behavioral domain, there are 4 scores: frequency (1-4), severity (1-3), domain total score (frequency x severity), and occupational disruptiveness (0-5), with lower scores indicating fewer symptoms. Thus, the NPI-NH evaluates response to therapy and provides symptom severity and distress ratings for each symptom reported, as well as total severity and distress scores reflecting the sum of individual domain scores.
  • Neuropsychiatric Inventory (NPI) Caregiver version [ Time Frame: Baseline to 5 weeks ]
    NPI is designed to measure the neuropsychiatric symptoms and psychopathology of patients with Alzheimer's Disease when the patient is living with a caregiver. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains. A screening question is asked about each sub-domain. If the response is yes, indicating the patient has problems with a particular sub-domain of behavior, the caregiver is only then asked all the questions about that domain, rating the frequency of the symptoms on a 4-point scale, their severity on a 3-point scale, and the distress the symptom causes them on a 5-point scale. The NPI provides symptom frequency, severity and distress ratings for each symptom reported, and total scores reflecting the sum of individual domain scores. Lower scores indicate better neuropsychiatric state of a subject.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of Pulsed GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
Brief Summary This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Severe Alzheimer Disease
Intervention  ICMJE
  • Drug: GRF6019
    GRF6019 for IV infusion
  • Other: Placebo
    Placebo for IV infusion
    Other Name: Normal Saline
Study Arms  ICMJE
  • Experimental: GRF6019
    Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days.
    Intervention: Drug: GRF6019
  • Placebo Comparator: Placebo
    Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 20, 2020)
26
Original Estimated Enrollment  ICMJE
 (submitted: December 4, 2018)
20
Actual Study Completion Date  ICMJE December 17, 2019
Actual Primary Completion Date December 17, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of probable AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria
  • MMSE Score 0-10 inclusive
  • Modified Hachinski Ischemia Scale (MHIS) score of 4 or less
  • Provided a signed and dated informed consent form (either the subject and/or subject's legal representative)

Exclusion Criteria:

  • Evidence of clinically relevant neurological disorder(s) other than probable AD
  • History of blood coagulation disorders or hypercoagulability; any concurrent use of an anticoagulant therapy. (e.g., heparin, warfarin, thrombin inhibitors, Factor Xa inhibitors). Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is acceptable.
  • Unstable coronary heart disease, e.g. myocardial infarction or severe or unstable angina in the 6 months prior to dosing.
  • Moderate to severe congestive heart failure (New York Association Class III or IV).
  • Poorly controlled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher) despite treatment during the 3 months prior to dosing, or treatment refractory high blood pressure, defined as treatment requiring 3 or more antihypertensives from different classes.
  • Prior hypersensitivity reaction to any human blood product or intravenous infusion; any known clinically significant drug allergy.
  • Treatment with any human blood product, including transfusions and intravenous immunoglobulin, during the 6 months prior to screening.
  • History of immunoglobulin A (IgA), haptoglobulin or C1 inhibitor deficiency; stroke, anaphylaxis, or thromboembolic complications of intravenous immunoglobulins.
  • Hemoglobin <10 g/dL in women; and <11 g/dL in men.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03765762
Other Study ID Numbers  ICMJE Alkahest study 6019-202
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alkahest, Inc.
Study Sponsor  ICMJE Alkahest, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alkahest Program Physician Alkahest, Inc.
PRS Account Alkahest, Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP