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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
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.

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.

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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

Resource links provided by the National Library of Medicine


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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520998


Locations
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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
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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

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Responsible Party: Alkahest, Inc.
ClinicalTrials.gov Identifier: NCT03520998    
Other Study ID Numbers: ALK6019-201
First Posted: May 11, 2018    Key Record Dates
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders