Back to resultsA Randomized Study to Assess the Safety of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease
Primary Purpose
Alzheimer Disease, Mild to Moderate Alzheimer Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GRF6019
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of probable AD based upon the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria
- MMSE Score 12-24 inclusive
- Modified Hachinski Ischemia Scale (MHIS) score of ≤ 4
- Provided a signed and dated informed consent form (either the subject and/or subject's legal representative as well as the trial partner)
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.
- Initiation or change in the dosage of cholinesterase inhibitors (AChEI), memantine, Axona, vitamin E supplementation or selegiline within 3 months prior to screening.
- Heart disease (or history thereof), as evidenced by myocardial infarction, unstable, new onset or severe angina, or congestive heart failure (New York Association Class II, III or IV) in the 6 months prior to dosing; uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood
- 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
- Synergy East
- CNS Network
- Pacific Research Network
- MD Clinical
- Miami Jewish Health Systems
- Behavioral Clinical Research
- Bioclinica Research
- Princeton Medical Institute
- Serenity Inpatient
- PRA Health Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
GRF6019 Low Dose
GRF6019 High Dose
Arm Description
Subjects will receive a low dose of GRF6019 for 5 consecutive days at Week 1 and Week 13.
Subjects will receive a high dose of GRF6019 for 5 consecutive days at Week 1 and Week 13.
Outcomes
Primary Outcome Measures
Frequency of Treatment-emergent Adverse Events (Safety)
Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class
Secondary Outcome Measures
The Mini-Mental State Examination (MMSE)
Changes in scores on the MMSE. 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 cognition.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog/11)
Changes in scores on the 11-item ADASCog/11. The ADAS-Cog/11 includes 11 items assessing cognitive function. The domains include memory, language, praxis, and orientation. There are 70 possible points. Higher scores reflect greater cognitive impairment.
The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB)
Changes in the CDR-SOB. The CDR characterizes functioning in 6 domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. The score is obtained by summing each of the domain box scores. Scores range from 0 to 18 with higher scores reflecting worse cognition.
The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)
Changes in the ADCS-ADL23. The ADCS-ADL23 assesses basic and instrumental activities of daily living covering physical and mental functioning and independence in self-care. The score ranges from 0 to 78 with higher scores indicating less functional impairment.
The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
The ADCS-CGIC focuses 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 7-point scale with lower values (<4) representing an improvement, higher values (>4) representing a worsening, and a value of 4 indicating no change.
The Neuropsychiatric Inventory Questionnaire (NPI-Q)
Change on the NPI-Q. The NPI-Q comprises 12 domains: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressivity and restlessness, irritability, anxiety aberrant motor behavior, appetite and eating disorders, and nocturnal behavior. The severity of the reported symptoms is assessed on a 3-point scale. The total severity score can range from 0 to 36 with higher scores representing worse severity.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03520998
Brief Title
A Randomized Study to Assess the Safety of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease
Official Title
A Prospective, Randomized, Double-Blind, Dose-Comparison Concurrent Control Study to Assess the Safety and Tolerability of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
April 16, 2018 (Actual)
Primary Completion Date
May 24, 2019 (Actual)
Study Completion Date
May 24, 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 is evaluating the safety, tolerability, and feasibility of GRF6019, a plasma-derived product, administered as an intravenous (IV) infusion, to subjects with mild to moderate Alzheimer's disease.
Detailed Description
This is a randomized, double-blind, dose-comparison concurrent control study to assess the safety, tolerability, and feasibility of GRF6019, a plasma-derived product, administered by intravenous (IV) infusion to subjects with mild to moderate Alzheimer's disease.
Subjects will be randomized 1:1 to a low dose or a high dose of active treatment in a double-blind manner. All subjects will receive one infusion per day at the randomized dose for 5 consecutive days during Week 1 and, again, during Week 13 (for a total of 10 doses per subject). All IV infusions will take place at an inpatient research unit while the follow-up visits after each treatment period will be on an outpatient basis. Subjects will participate for a total of 6 months in this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Mild to Moderate Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GRF6019 Low Dose
Arm Type
Experimental
Arm Description
Subjects will receive a low dose of GRF6019 for 5 consecutive days at Week 1 and Week 13.
Arm Title
GRF6019 High Dose
Arm Type
Experimental
Arm Description
Subjects will receive a high dose of GRF6019 for 5 consecutive days at Week 1 and Week 13.
Intervention Type
Drug
Intervention Name(s)
GRF6019
Intervention Description
GRF6019 for IV infusion
Primary Outcome Measure Information:
Title
Frequency of Treatment-emergent Adverse Events (Safety)
Description
Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
The Mini-Mental State Examination (MMSE)
Description
Changes in scores on the MMSE. 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 cognition.
Time Frame
Baseline and 6 months
Title
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog/11)
Description
Changes in scores on the 11-item ADASCog/11. The ADAS-Cog/11 includes 11 items assessing cognitive function. The domains include memory, language, praxis, and orientation. There are 70 possible points. Higher scores reflect greater cognitive impairment.
Time Frame
Baseline and 6 months
Title
The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB)
Description
Changes in the CDR-SOB. The CDR characterizes functioning in 6 domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. The score is obtained by summing each of the domain box scores. Scores range from 0 to 18 with higher scores reflecting worse cognition.
Time Frame
Baseline and 6 months
Title
The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)
Description
Changes in the ADCS-ADL23. The ADCS-ADL23 assesses basic and instrumental activities of daily living covering physical and mental functioning and independence in self-care. The score ranges from 0 to 78 with higher scores indicating less functional impairment.
Time Frame
Baseline and 6 months
Title
The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
Description
The ADCS-CGIC focuses 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 7-point scale with lower values (<4) representing an improvement, higher values (>4) representing a worsening, and a value of 4 indicating no change.
Time Frame
Baseline and 6 months
Title
The Neuropsychiatric Inventory Questionnaire (NPI-Q)
Description
Change on the NPI-Q. The NPI-Q comprises 12 domains: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressivity and restlessness, irritability, anxiety aberrant motor behavior, appetite and eating disorders, and nocturnal behavior. The severity of the reported symptoms is assessed on a 3-point scale. The total severity score can range from 0 to 36 with higher scores representing worse severity.
Time Frame
Baseline and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of probable AD based upon the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria
MMSE Score 12-24 inclusive
Modified Hachinski Ischemia Scale (MHIS) score of ≤ 4
Provided a signed and dated informed consent form (either the subject and/or subject's legal representative as well as the trial partner)
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.
Initiation or change in the dosage of cholinesterase inhibitors (AChEI), memantine, Axona, vitamin E supplementation or selegiline within 3 months prior to screening.
Heart disease (or history thereof), as evidenced by myocardial infarction, unstable, new onset or severe angina, or congestive heart failure (New York Association Class II, III or IV) in the 6 months prior to dosing; uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood
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 Medical Monitor
Organizational Affiliation
Alkahest, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Synergy East
City
Lemon Grove
State/Province
California
ZIP/Postal Code
91945
Country
United States
Facility Name
CNS Network
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Pacific Research Network
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
MD Clinical
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
Miami Jewish Health Systems
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Facility Name
Behavioral Clinical Research
City
North Miami
State/Province
Florida
ZIP/Postal Code
33161
Country
United States
Facility Name
Bioclinica Research
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Princeton Medical Institute
City
Princeton
State/Province
New Jersey
ZIP/Postal Code
08540
Country
United States
Facility Name
Serenity Inpatient
City
DeSoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
Facility Name
PRA Health Sciences
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84124
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Randomized Study to Assess the Safety of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease
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