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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease; Mild to Moderate Alzheimer Disease
• Intervention / Treatment: Drug: GRF6019

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 Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Lemon Grove, California, United States, 91945
      • Synergy East
    • Long Beach, California, United States, 90806
      • CNS Network
    • San Diego, California, United States, 92103
      • Pacific Research Network
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems
    • North Miami, Florida, United States, 33161
      • Behavioral Clinical Research
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
  • Texas
    • DeSoto, Texas, United States, 75115
      • Serenity Inpatient
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alkahest, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Actual): May 24, 2019
• Study Completion (Actual): May 24, 2019

Study Registration Dates

• First Submitted: April 25, 2018
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 8, 2021
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: ALK6019-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No