Clinical trial NCT02431468: A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease
Official title: A Randomized, Double-Blind,Placebo-Controlled, Phase 2 Study Assessing the Safety, Tolerability and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Neurotrope Bioscience, Inc.
Sponsor class: INDUSTRY
First posted: 2015-05-01
Enrollment: 147
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Written informed consent from caregiver and subject (if possible) or legally acceptable representative if different from caregiver
* Male and female subjects 55-85 years of age inclusive
* Cognitive deficit present for at least 2 years that meet the diagnostic criteria for probable Alzheimer's
* Mini Mental State Exam (MMSE-2) score of 4-15
* Patients must be able to perform at least one item on the Severe Impairment Battery Scale
* Neuroimaging (computerized tomography (CT) or Magnetic Resonance Imaging (MRI)) within the last 24 months consistent with a diagnosis of probable Alzheimer's disease (AD)
* Reliable caregiver(s) or informant(s) who attends the subject at least an average of 3 hours or more per day for 3 or more days per week
* Adequate vision and motor function to comply with testing
* If taking drugs approved for treatment of Alzheimer's disease (e.g. cholinesterase inhibitors, memantine), must be on a stable dose for at least 3 months prior to entry into study and the dose must not change during the study unless a change is required due to an adverse event or a clinically significant change in the patient's status.

Exclusion Criteria:

* Dementia due to any condition other than AD, including vascular dementia (Rosen-modified Hachinski lschemic score ≥ 5)
* Evidence of significant central nervous system (CNS) vascular disease on previous neuroimaging including but not limited to: cortical stroke, multiple infarcts, localized single infarcts in the thalamus, angular gyrus, multiple lacunar infarcts or extensive white matter injury
* Clinically significant neurologic disease or condition other than AD, such as cerebral tumor, chronic subdural fluid collections, Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, or any other diagnosis that could interfere with assessment of safety and efficacy
* Evidence of clinically significant unstable cardiovascular, pulmonary, renal, hepatic, gastrointestinal, neurologic, or metabolic disease within the 6 months prior to enrollment
* Poorly controlled diabetes, at the discretion of the Principal Investigator
* Creatinine clearance (CL) of \<45ml/min
* Use of an active Alzheimer's vaccine within 2 years prior to screening
* Use of a monoclonal antibody for treatment of AD within 1 year prior to screening
* Any medical or psychiatric condition that is likely to require initiation of additional medication or surgical intervention during the course of the study
* Use of an investigational drug within 30 days prior to screening
* Prior exposure to bryostatin, or known sensitivity to bryostatin or any ingredient in the study drug
* Any other concurrent medical condition, which in the opinion of the PI makes the subject unsuitable for the clinical study

Primary outcomes:
measure: Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events
timeFrame: Baseline through 30 days post end of treatment (up to Day 107)
measure: Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS)
timeFrame: Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107)
Secondary outcomes:
measure: Secondary Efficacy Endpoints
timeFrame: Week 5, Week 9, Week 13
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc/ 21st Century Neurology
state: Arizona
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Los Alamitos
country: United States
facility: Nader Pharmacology Research Institute
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Atlantis
country: United States
facility: JEM Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of South Florida
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health System
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: The Villages
country: United States
facility: Compass Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Institute Clinical Research
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Alzheimer's Disease Center
state: Kansas
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Shreveport
country: United States
facility: J. Gary Booker, MD APMC Clinical Drug Trials
state: Louisiana
city: Creve Coeur
country: United States
facility: Millennium Psychiatric Associates
state: Missouri
city: Springfield
country: United States
facility: Atlantic Neuroscience Institute
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: New Hyde Park
country: United States
facility: Parker Jewish Institute for Health Care and Rehabilitation
state: New York
city: Charlotte
country: United States
facility: Alzheimer's Memory Center
state: North Carolina
city: Canton
country: United States
facility: Neurobehavioral Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Medford
country: United States
facility: Sunstone Clinical Research
state: Oregon
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
Study officials:
References: