NCT02431468

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
147

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2015

Shorter than P25 for phase_2

Geographic Reach
1 country

29 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 22, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

May 1, 2015

Completed
6 months until next milestone

Study Start

First participant enrolled

November 1, 2015

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

July 6, 2018

Completed
Last Updated

July 6, 2018

Status Verified

June 1, 2018

Enrollment Period

1.3 years

First QC Date

April 22, 2015

Results QC Date

April 30, 2018

Last Update Submit

June 6, 2018

Conditions

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (1)

  • Secondary Efficacy Endpoints

    Week 5, Week 9, Week 13

Study Arms (3)

Bryostatin 1 20ug

EXPERIMENTAL

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

Bryostatin 1 40ug

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

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.

Also known as: bryostatin
Bryostatin 1 20ugBryostatin 1 40ug
PlaceboOTHER

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

Placebo

Eligibility Criteria

Age55 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Xenoscience, Inc/ 21st Century Neurology

Phoenix, Arizona, 85004, United States

Location

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Nader Pharmacology Research Institute

Los Alamitos, California, 90720, United States

Location

San Francisco Clinical Research Center

San Francisco, California, 94109, United States

Location

JEM Research

Atlantis, Florida, 33462, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research Center of South Florida

Fort Myers, Florida, 33912, United States

Location

Alzheimer's Research and Treatment Center

Lake Worth, Florida, 33449, United States

Location

Miami Jewish Health System

Miami, Florida, 33137, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

Compass Research, LLC

Orlando, Florida, 32806, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, 33609, United States

Location

Compass Research

The Villages, Florida, 32162, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

iResearch Atlanta

Decatur, Georgia, 30030, United States

Location

Alexian Brothers Neurosciences Institute Clinical Research

Elk Grove Village, Illinois, 60007, United States

Location

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, 66205, United States

Location

Lake Charles Clinical Trials

Lake Charles, Louisiana, 70629, United States

Location

J. Gary Booker, MD APMC Clinical Drug Trials

Shreveport, Louisiana, 71104, United States

Location

Millennium Psychiatric Associates

Creve Coeur, Missouri, 63141, United States

Location

Atlantic Neuroscience Institute

Springfield, New Jersey, 07801, United States

Location

Neurological Associates of Albany, PC

Albany, New York, 12208, United States

Location

Parker Jewish Institute for Health Care and Rehabilitation

New Hyde Park, New York, 11040, United States

Location

Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Neurobehavioral Clinical Research

Canton, Ohio, 44718, United States

Location

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, 73112, United States

Location

Sunstone Clinical Research

Medford, Oregon, 97504, United States

Location

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, United States

Location

Neurology Clinic, PC

Cordova, Tennessee, 38018, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

bryostatin 1Bryostatins

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Polyether ToxinsPolyether PolyketidesEthers, CyclicEthersOrganic ChemicalsMacrolidesPolyketidesLactonesMacrocyclic CompoundsPolycyclic CompoundsMarine ToxinsToxins, BiologicalBiological Factors

Results Point of Contact

Title
David Crockford, Vice President, Regulatory Affairs
Organization
Neurotrope BioScience, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 22, 2015

First Posted

May 1, 2015

Study Start

November 1, 2015

Primary Completion

February 1, 2017

Study Completion

February 1, 2017

Last Updated

July 6, 2018

Results First Posted

July 6, 2018

Record last verified: 2018-06

Locations