ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03765762
Recruitment Status : Recruiting
First Posted : December 5, 2018
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
Alkahest, Inc.

Brief Summary:
This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Severe Alzheimer Disease Drug: GRF6019 Other: Placebo Phase 2

Detailed Description:
This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability and potential cognitive benefit of GRF6019, a human plasma protein fraction. GRF6019 or placebo will be administered intravenously to subjects with severe Alzheimer's disease every day for 5 consecutive days. The total study duration for each subject is approximately 9 weeks.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of Pulsed GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GRF6019
Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days.
Drug: GRF6019
GRF6019 for IV infusion

Placebo Comparator: Placebo
Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days.
Other: Placebo
Placebo for IV infusion




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (safety) [ Time Frame: Baseline to 5 weeks ]
    Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class

  2. Tolerability of GRF6019 as assessed by number of patients completing the dosing regimen [ Time Frame: Baseline to 5 weeks ]
    Number of subjects completing 4 weeks after receiving 5 infusions


Secondary Outcome Measures :
  1. The Mini-Mental State Examination (MMSE) score [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the MMSE score. The MMSE is a 30-point questionnaire used to measure the extent of cognitive impairment. Lower scores indicate more severe cognitive impairment.

  2. Severe Impairment Battery (SIB) [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the SIB score. The SIB assesses cognition; test questions measure orientation, attention, language, praxis, visuospatial perception, construction, memory, orientation to name, and social interaction. There are 57 items and the range of possible scores is 0-133. Lower scores indicate greater cognitive impairment.

  3. Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe) [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the ADCS-ADL-Severe score. The ADCS-ADL-Severe contains 19 items covering physical and mental functioning and independence in self-care and assesses the competence in performing basic activities of daily living. The scores range from 0 to 54, with higher scores indicating less functional impairment.

  4. Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC) [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the ADCS-CGIC score. A CGIC score is based on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial.The ADCS-CGIC is a rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the patient and informant to make a global impression of change. After completing the interviews, the clinician records the clinical impression of change on a 7-point Likert-type scale (from marked improvement to marked worsening).

  5. Neuropsychiatric Inventory Nursing Home (NPI-NH) Version [ Time Frame: Baseline to 5 weeks ]
    Changes from baseline in the NPI-NH score. NPI-NH consists of 12 behavioral domains and is to assess psychiatric symptoms in patients with dementia in outpatient settings. For each behavioral domain, there are 4 scores: frequency (1-4), severity (1-3), domain total score (frequency x severity), and occupational disruptiveness (0-5), with lower scores indicating fewer symptoms. Thus, the NPI-NH evaluates response to therapy and provides symptom severity and distress ratings for each symptom reported, as well as total severity and distress scores reflecting the sum of individual domain scores.

  6. Neuropsychiatric Inventory (NPI) Caregiver version [ Time Frame: Baseline to 5 weeks ]
    NPI is designed to measure the neuropsychiatric symptoms and psychopathology of patients with Alzheimer's Disease when the patient is living with a caregiver. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains. A screening question is asked about each sub-domain. If the response is yes, indicating the patient has problems with a particular sub-domain of behavior, the caregiver is only then asked all the questions about that domain, rating the frequency of the symptoms on a 4-point scale, their severity on a 3-point scale, and the distress the symptom causes them on a 5-point scale. The NPI provides symptom frequency, severity and distress ratings for each symptom reported, and total scores reflecting the sum of individual domain scores. Lower scores indicate better neuropsychiatric state of a subject.



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.


Ages Eligible for Study:   60 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of probable AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria
  • MMSE Score 0-10 inclusive
  • Modified Hachinski Ischemia Scale (MHIS) score of 4 or less
  • Provided a signed and dated informed consent form (either the subject and/or subject's legal representative)

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.
  • Unstable coronary heart disease, e.g. myocardial infarction or severe or unstable angina in the 6 months prior to dosing.
  • Moderate to severe congestive heart failure (New York Association Class III or IV).
  • Poorly controlled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher) despite treatment during the 3 months prior to dosing, or treatment refractory high blood pressure, defined as treatment requiring 3 or more antihypertensives from different classes.
  • 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): NCT03765762


Contacts
Contact: Alkahest Clinical Trials 650-801-0474 trials@alkahest.com

Locations
United States, Arizona
Cognitive Clinical Trials Recruiting
Gilbert, Arizona, United States, 85297
Contact: Brian Beck, MD       brianbeck@cctresearch.com   
Cognitive Clinical Trials Recruiting
Mesa, Arizona, United States, 85209
Contact: Brian Beck, MD       brianbeck@cctresearch.com   
Cognitive Clinical Trials Recruiting
Phoenix, Arizona, United States, 85037
Contact: Brian Beck, MD       brianbeck@cctresearch.com   
United States, Florida
Riverside Clinical Research Recruiting
Edgewater, Florida, United States, 32132
Contact: James Scott, MD       pi14@interspond.com   
Sponsors and Collaborators
Alkahest, Inc.
Investigators
Study Director: Alkahest Program Physician Alkahest, Inc.

Responsible Party: Alkahest, Inc.
ClinicalTrials.gov Identifier: NCT03765762     History of Changes
Other Study ID Numbers: Alkahest study 6019-202
First Posted: December 5, 2018    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 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

Keywords provided by Alkahest, Inc.:
Brain Diseases
Nervous System Diseases
Central Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Dementia
Tauopathy

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders