Back to resultsA Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
Primary Purpose
Severe Alzheimer Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GRF6019
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Severe Alzheimer Disease focused on measuring Brain Diseases, Nervous System Diseases, Central Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Dementia, Tauopathy
Eligibility Criteria
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.
Sites / Locations
- Cognitive Clinical Trials
- Cognitive Clinical Trials
- Cognitive Clinical Trials
- Pacific Research Network
- Riverside Clinical Research
- Bio Behavioral Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
GRF6019
Placebo
Arm Description
Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days.
Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days.
Outcomes
Primary Outcome Measures
Frequency of Treatment-emergent Adverse Events (Safety)
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
Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
Secondary Outcome Measures
The Mini-Mental State Examination (MMSE) Score
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
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)
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)
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03765762
Brief Title
A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
January 15, 2019 (Actual)
Primary Completion Date
December 17, 2019 (Actual)
Study Completion Date
December 17, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alkahest, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Alzheimer Disease
Keywords
Brain Diseases, Nervous System Diseases, Central Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Dementia, Tauopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GRF6019
Arm Type
Experimental
Arm Description
Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days.
Intervention Type
Drug
Intervention Name(s)
GRF6019
Intervention Description
GRF6019 for IV infusion
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline
Intervention Description
Placebo for IV infusion
Primary Outcome Measure Information:
Title
Frequency of Treatment-emergent Adverse Events (Safety)
Description
Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class
Time Frame
5 weeks
Title
Tolerability of GRF6019
Description
Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
Time Frame
5 weeks
Secondary Outcome Measure Information:
Title
The Mini-Mental State Examination (MMSE) Score
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.
Time Frame
Baseline and 5 weeks
Title
Severe Impairment Battery (SIB) Total Score
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.
Time Frame
Baseline and 5 weeks
Title
Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)
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.
Time Frame
Baseline and 5 weeks
Title
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)
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.
Time Frame
Baseline and 5 weeks
Title
Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score
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.
Time Frame
Baseline and 5 weeks
Title
Neuropsychiatric Inventory (NPI) Caregiver Total Score
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.
Time Frame
Baseline and 5 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alkahest Program Physician
Organizational Affiliation
Alkahest, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cognitive Clinical Trials
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85297
Country
United States
Facility Name
Cognitive Clinical Trials
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85209
Country
United States
Facility Name
Cognitive Clinical Trials
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85037
Country
United States
Facility Name
Pacific Research Network
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Riverside Clinical Research
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Facility Name
Bio Behavioral Health
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
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