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

• ClinicalTrials.gov Identifier: NCT03520998
• Recruitment Status: Completed
• First Posted: May 11, 2018
• Results First Posted: November 5, 2020
• Last Update Posted: January 29, 2021
• Sponsor: Alkahest, Inc.
• Information provided by (Responsible Party): Alkahest, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease; Mild to Moderate Alzheimer Disease	Drug: GRF6019	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 16, 2018
• Actual Primary Completion Date: May 24, 2019
• Actual Study Completion Date: May 24, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Frequency of Treatment-emergent Adverse Events (Safety) [ Time Frame: Baseline to 6 months ]
   Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class

Secondary Outcome Measures :

1. The Mini-Mental State Examination (MMSE) [ Time Frame: 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.
2. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog/11) [ Time Frame: 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.
3. The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB) [ Time Frame: 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.
4. The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 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.
5. The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 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.
6. The Neuropsychiatric Inventory Questionnaire (NPI-Q) [ Time Frame: 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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, California

Synergy East

Lemon Grove, California, United States, 91945

CNS Network

Long Beach, California, United States, 90806

Pacific Research Network

San Diego, California, United States, 92103

United States, Florida

MD Clinical

Hallandale Beach, Florida, United States, 33009

Miami Jewish Health Systems

Miami, Florida, United States, 33137

Behavioral Clinical Research

North Miami, Florida, United States, 33161

Bioclinica Research

Orlando, Florida, United States, 32806

United States, New Jersey

Princeton Medical Institute

Princeton, New Jersey, United States, 08540

United States, Texas

Serenity Inpatient

DeSoto, Texas, United States, 75115

United States, Utah

PRA Health Sciences

Salt Lake City, Utah, United States, 84124

Sponsors and Collaborators

Alkahest, Inc.

Investigators

• Study Director: Alkahest Medical Monitor; Alkahest, Inc.

  Study Documents (Full-Text)

Documents provided by Alkahest, Inc.:

Study Protocol  [PDF] November 2, 2018

Statistical Analysis Plan  [PDF] June 9, 2019

More Information

• Responsible Party: Alkahest, Inc.
• ClinicalTrials.gov Identifier: NCT03520998
• Other Study ID Numbers: ALK6019-201
• First Posted: May 11, 2018
• Results First Posted: November 5, 2020
• Last Update Posted: January 29, 2021
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders