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

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bryostatin 1
Placebo
Sponsored by
Neurotrope Bioscience, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Xenoscience, Inc/ 21st Century Neurology
  • ATP Clinical Research, Inc.
  • Nader Pharmacology Research Institute
  • San Francisco Clinical Research Center
  • JEM Research
  • Brain Matters Research
  • Neuropsychiatric Research Center of South Florida
  • Alzheimer's Research and Treatment Center
  • Miami Jewish Health System
  • Medical Research Group of Central Florida
  • Compass Research, LLC
  • Axiom Clinical Research of Florida
  • Compass Research
  • Atlanta Center for Medical Research
  • iResearch Atlanta
  • Alexian Brothers Neurosciences Institute Clinical Research
  • University of Kansas Alzheimer's Disease Center
  • Lake Charles Clinical Trials
  • J. Gary Booker, MD APMC Clinical Drug Trials
  • Millennium Psychiatric Associates
  • Atlantic Neuroscience Institute
  • Neurological Associates of Albany, PC
  • Parker Jewish Institute for Health Care and Rehabilitation
  • Alzheimer's Memory Center
  • Neurobehavioral Clinical Research
  • Oklahoma Clinical Research Center
  • Sunstone Clinical Research
  • The Clinical Trial Center, LLC
  • Neurology Clinic, PC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Bryostatin 1 20ug

Bryostatin 1 40ug

Placebo

Arm Description

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.

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.

Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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.

Full Information

First Posted
April 22, 2015
Last Updated
June 6, 2018
Sponsor
Neurotrope Bioscience, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02431468
Brief Title
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

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
February 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurotrope Bioscience, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
147 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bryostatin 1 20ug
Arm Type
Experimental
Arm Description
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.
Arm Title
Bryostatin 1 40ug
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Bryostatin 1
Other Intervention Name(s)
bryostatin
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Primary Outcome Measure Information:
Title
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events
Description
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)
Title
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS)
Description
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 Outcome Measure Information:
Title
Secondary Efficacy Endpoints
Description
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.
Time Frame
Week 5, Week 9, Week 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Xenoscience, Inc/ 21st Century Neurology
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85004
Country
United States
Facility Name
ATP Clinical Research, Inc.
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Nader Pharmacology Research Institute
City
Los Alamitos
State/Province
California
ZIP/Postal Code
90720
Country
United States
Facility Name
San Francisco Clinical Research Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
JEM Research
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Brain Matters Research
City
Delray Beach
State/Province
Florida
ZIP/Postal Code
33445
Country
United States
Facility Name
Neuropsychiatric Research Center of South Florida
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
Facility Name
Alzheimer's Research and Treatment Center
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33449
Country
United States
Facility Name
Miami Jewish Health System
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Facility Name
Medical Research Group of Central Florida
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
Facility Name
Compass Research, LLC
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Axiom Clinical Research of Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
Compass Research
City
The Villages
State/Province
Florida
ZIP/Postal Code
32162
Country
United States
Facility Name
Atlanta Center for Medical Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30331
Country
United States
Facility Name
iResearch Atlanta
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
Alexian Brothers Neurosciences Institute Clinical Research
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
University of Kansas Alzheimer's Disease Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Lake Charles Clinical Trials
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70629
Country
United States
Facility Name
J. Gary Booker, MD APMC Clinical Drug Trials
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71104
Country
United States
Facility Name
Millennium Psychiatric Associates
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Atlantic Neuroscience Institute
City
Springfield
State/Province
New Jersey
ZIP/Postal Code
07801
Country
United States
Facility Name
Neurological Associates of Albany, PC
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Parker Jewish Institute for Health Care and Rehabilitation
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Alzheimer's Memory Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28270
Country
United States
Facility Name
Neurobehavioral Clinical Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Oklahoma Clinical Research Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Sunstone Clinical Research
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
The Clinical Trial Center, LLC
City
Jenkintown
State/Province
Pennsylvania
Country
United States
Facility Name
Neurology Clinic, PC
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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