A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02431468
• Other study ID #: NTRP-101-202
• Status: Completed
• Phase: Phase 2
• Start date: November 2015
• Est. completion date: February 2017

Study information

• Verified date: June 2018
• Source: Neurotrope Bioscience, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Bryostatin 1
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.

Other:
• Placebo
The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.

Locations

Country	Name	City	State
United States	Neurological Associates of Albany, PC	Albany	New York
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	JEM Research	Atlantis	Florida
United States	Neurobehavioral Clinical Research	Canton	Ohio
United States	Alzheimer's Memory Center	Charlotte	North Carolina
United States	Neurology Clinic, PC	Cordova	Tennessee
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Millennium Psychiatric Associates	Creve Coeur	Missouri
United States	iResearch Atlanta	Decatur	Georgia
United States	Brain Matters Research	Delray Beach	Florida
United States	Alexian Brothers Neurosciences Institute Clinical Research	Elk Grove Village	Illinois
United States	University of Kansas Alzheimer's Disease Center	Fairway	Kansas
United States	Neuropsychiatric Research Center of South Florida	Fort Myers	Florida
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	Lake Charles Clinical Trials	Lake Charles	Louisiana
United States	Alzheimer's Research and Treatment Center	Lake Worth	Florida
United States	Nader Pharmacology Research Institute	Los Alamitos	California
United States	Sunstone Clinical Research	Medford	Oregon
United States	Miami Jewish Health System	Miami	Florida
United States	Parker Jewish Institute for Health Care and Rehabilitation	New Hyde Park	New York
United States	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	Compass Research, LLC	Orlando	Florida
United States	Xenoscience, Inc/ 21st Century Neurology	Phoenix	Arizona
United States	San Francisco Clinical Research Center	San Francisco	California
United States	J. Gary Booker, MD APMC Clinical Drug Trials	Shreveport	Louisiana
United States	Atlantic Neuroscience Institute	Springfield	New Jersey
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Compass Research	The Villages	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Neurotrope Bioscience, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline through 30 days post end of treatment (up to Day 107)
Primary	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.	Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107)
Secondary	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.	Week 5, Week 9, Week 13