Severe Alzheimer Disease Clinical Trial
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
| Verified date | May 2019 |
| Source | Alkahest, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease.
| Status | Completed |
| Enrollment | 26 |
| Est. completion date | December 17, 2019 |
| Est. primary completion date | December 17, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 60 Years to 95 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Riverside Clinical Research | Edgewater | Florida |
| United States | Cognitive Clinical Trials | Gilbert | Arizona |
| United States | Cognitive Clinical Trials | Mesa | Arizona |
| United States | Cognitive Clinical Trials | Phoenix | Arizona |
| United States | Pacific Research Network | San Diego | California |
| United States | Bio Behavioral Health | Toms River | New Jersey |
| Lead Sponsor | Collaborator |
|---|---|
| Alkahest, Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Frequency of Treatment-emergent Adverse Events (Safety) | Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class | 5 weeks | |
| Primary | Tolerability of GRF6019 | Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions | 5 weeks | |
| Secondary | The Mini-Mental State Examination (MMSE) Score | Mean change from Baseline to 5 Weeks in the Mini-Mental State Examination (MMSE) score. 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 mental status. | Baseline and 5 weeks | |
| Secondary | Severe Impairment Battery (SIB) Total Score | Mean change from baseline in the SIB total 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. | Baseline and 5 weeks | |
| Secondary | Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe) | Mean change 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. | Baseline and 5 weeks | |
| Secondary | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC) | Mean ADCS-CGIC score. A CGIC score is based 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 rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the subject 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). A score of 4 indicates no change, while scores > 4 indicate worsening and scores < 4 indicate improvement. | Baseline and 5 weeks | |
| Secondary | Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score | Mean change from Baseline to 5 weeks in the NPI-NH total score. The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains (Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor Behavior, Sleep and Nighttime Behavior Disorders, Appetite/Eating Changes). For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), with a possible summed total score of 0 to 144. Lower scores correspond to less severity. A negative change score from baseline indicates improvement. | Baseline and 5 weeks | |
| Secondary | Neuropsychiatric Inventory (NPI) Caregiver Total Score | Mean change from Baseline to 5 Weeks in NPI Total Score. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains (Delusions, Hallucinations, Agitation/Aggression, Dysphoria/Depression, Anxiety, Euphoria/Elation, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor, Nighttime Behavior, Appetite/Eating). For each of the 12 behavioral domains the Distress (scale:0=Not distressing at all to 5=Extreme) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (distress x severity), with a possible summed total score of 0 to 180. Lower scores correspond to less severity. A negative change score from baseline indicates improvement. | Baseline and 5 weeks |