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

Phase 2

Completed

• Conditions: Mild to Moderate Alzheimer Disease; Alzheimer Disease
• Interventions: Drug: GRF6019

• Registration Number: NCT03520998
• Lead Sponsor: Alkahest, Inc.

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.

Study Timeline

• Study Start: 2018-04-16
• Study First Submitted: 2018-04-25
• Study First Submitted QC: 2018-05-08
• Study First Posted: 2018-05-11
• Status Verified: 2018-08
• Primary Completion: 2019-05-24
• Study Completion: 2019-05-24
• Results First Submitted: 2020-10-05
• Results First Submitted QC: 2020-10-13
• Results First Posted: 2020-11-05
• Last Update Submitted: 2021-01-08
• Last Update Posted: 2021-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GRF6019 High Dose	GRF6019	Subjects will receive a high dose of GRF6019 for 5 consecutive days at Week 1 and Week 13.
GRF6019 Low Dose	GRF6019	Subjects will receive a low dose of GRF6019 for 5 consecutive days at Week 1 and Week 13.

Primary Outcome Measures

Name	Time	Method
Frequency of Treatment-emergent Adverse Events (Safety)	Baseline to 6 months	Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class

Secondary Outcome Measures

Name	Time	Method
The Mini-Mental State Examination (MMSE)	Baseline and 6 months	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)	Baseline and 6 months	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)	Baseline and 6 months	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)	Baseline and 6 months	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)	Baseline and 6 months	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)	Baseline and 6 months	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.

Trial Locations

Locations (10)

Princeton Medical Institute; 🇺🇸 Princeton, New Jersey, United States

CNS Network; 🇺🇸 Long Beach, California, United States

Synergy East; 🇺🇸 Lemon Grove, California, United States

Behavioral Clinical Research; 🇺🇸 North Miami, Florida, United States

Pacific Research Network; 🇺🇸 San Diego, California, United States

MD Clinical; 🇺🇸 Hallandale Beach, Florida, United States

Miami Jewish Health Systems; 🇺🇸 Miami, Florida, United States

Serenity Inpatient; 🇺🇸 DeSoto, Texas, United States

Bioclinica Research; 🇺🇸 Orlando, Florida, United States

PRA Health Sciences; 🇺🇸 Salt Lake City, Utah, United States