This is a randomized double-blind placebo-controlled study comparing different doses of bryostatin for the treatment of moderately severe to severe Alzheimer's disease. The study is 15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose of study drug.
This study will enroll 150 moderately severe to severe Alzheimer's disease subjects. Subjects will be randomly assigned 1:1:1 to treatment with two different doses of bryostatin 1 or placebo. The primary analysis will take place after 12 weeks of treatment (7 doses).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
147
The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.
The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events
Evaluations of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia
Time frame: Baseline through 30 days post end of treatment (up to Day 107)
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS)
The primary statistical objective for efficacy was to estimate the effect of bryostatin on the mean change in the total SIB score after 12 weeks of treatment, assessed at Week 13 (day 91). Efficacy analyses were conducted according to randomized groups. The SIB is used to assess cognition in subjects with moderate and severe AD. It is divided into nine subscales that include attention, language, orientation, memory, praxis, visuospatial ability, construction, social skills, orienting head to name. Non-verbal responses are allowed, thus decreasing the need for language output. Forty questions are included with a point score range of 0-100. Lower scores indicate greater cognitive impairment.
Time frame: Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107)
Secondary Efficacy Endpoints
* Change from baseline in the Severe Impairment Battery (SIB) at Weeks 5 and 9. Assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment. * Change from baseline in Alzheimer Disease Cooperative Study Activities of Daily Living Inventory-Severe Impairment Version (ADCS-ADL-SEV) at Weeks 5, 9,13. A 19-item test of the performance of activities of daily living. Total score range 0-54; lower scores indicate greater functional impairment. * Change from baseline in MMSE-2 at Weeks 5, 9 and 13. Tests selected aspects of cognition on a scale of 0-30. Lower scores indicate greater cognitive impairment. * Change from baseline in Neuropsychiatric Inventory (NPI) at Weeks 5, 9,13. Caregiver interview assesses 12 behavioral disturbances. Scores range from 0-144; higher scores indicate greater behavioral disturbances. * Clinical Global Impression of Improvement (CGI-I) at Weeks 5, 9, 13. A 7-point scale range from (1) very much improved to (7) very much worse.
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Xenoscience, Inc/ 21st Century Neurology
Phoenix, Arizona, United States
ATP Clinical Research, Inc.
Costa Mesa, California, United States
Nader Pharmacology Research Institute
Los Alamitos, California, United States
San Francisco Clinical Research Center
San Francisco, California, United States
JEM Research
Atlantis, Florida, United States
Brain Matters Research
Delray Beach, Florida, United States
Neuropsychiatric Research Center of South Florida
Fort Myers, Florida, United States
Alzheimer's Research and Treatment Center
Lake Worth, Florida, United States
Miami Jewish Health System
Miami, Florida, United States
Medical Research Group of Central Florida
Orange City, Florida, United States
...and 19 more locations
Time frame: Week 5, Week 9, Week 13