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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Bryostatin 1; Other: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc/ 21st Century Neurology
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Los Alamitos, California, United States, 90720
      • Nader Pharmacology Research Institute
    • San Francisco, California, United States, 94109
      • San Francisco Clinical Research Center
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of South Florida
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center
    • Miami, Florida, United States, 33137
      • Miami Jewish Health System
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • The Villages, Florida, United States, 32162
      • Compass Research
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Institute Clinical Research
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Alzheimer's Disease Center
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials
    • Shreveport, Louisiana, United States, 71104
      • J. Gary Booker, MD APMC Clinical Drug Trials
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Millennium Psychiatric Associates
  • New Jersey
    • Springfield, New Jersey, United States, 07801
      • Atlantic Neuroscience Institute
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany, PC
    • New Hyde Park, New York, United States, 11040
      • Parker Jewish Institute for Health Care and Rehabilitation
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • Alzheimer's Memory Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neurobehavioral Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Sunstone Clinical Research
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States
      • The Clinical Trial Center, LLC
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bryostatin 1 20ug; Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	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 Names: bryostatin
Experimental: Bryostatin 1 40ug; Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	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 Names: bryostatin
Placebo Comparator: Placebo; Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Neurotrope Bioscience, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Actual): July 6, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Bryostatin 1
• Other Study ID Numbers: NTRP-101-202