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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Alzheimer Disease, Mild to Moderate Alzheimer Disease

Intervention / Treatment
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* Drug: GRF6019


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GRF6019 Low Dose<br>Subjects will receive a low dose of GRF6019 for 5 consecutive days at Week 1 and Week 13. | Drug: GRF6019<br>* GRF6019 for IV infusion<br>|
| Experimental: GRF6019 High Dose<br>Subjects will receive a high dose of GRF6019 for 5 consecutive days at Week 1 and Week 13. | Drug: GRF6019<br>* GRF6019 for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Treatment-emergent Adverse Events (Safety) | Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 6 months | 
| 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. | Baseline and 6 months | 
| 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. | Baseline and 6 months | 
| 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. | Baseline and 6 months | 
| 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. | Baseline and 6 months | 
| 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. | Baseline and 6 months |