A Study of Bryostatin in Moderately Severe to Severe Alzheimer's Disease Subjects Not On Memantine

NCT03560245 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NTRP101-203
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 28

Brief Summary

This is a randomized double-blind Placebo-controlled, Phase 2 study comparing bryostatin to placebo for the treatment of moderately severe to severe Alzheimer's disease in subjects not receiving memantine treatment. The study is 15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose of study drug. Subjects will receive 7 doses of study drug during the study. The primary efficacy endpoint is defined as the change from baseline to Week 13 in the Severe Impairment Battery (SIB) total score.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Safety: Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Incidence 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: The Primary Efficacy Endpoint is Defined as the Change From Baseline to Week 13 in the Severe Impairment Battery (SIB) Total Score in the Full Analysis Set

  The Severe Impairment Battery (SIB) assesses cognition in subjects with moderate and severe Alzheimer's disease(AD). Test questions measure 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 total point score range of 0-100. Lower scores indicate greater cognitive impairment.

  The change in the SIB Total Score from baseline to Week 13 (Day 91)

Secondary Outcomes (4)

• The Changes From Baseline at Weeks 5, 9 and 15 in the Severe Impairment Battery (SIB) Total Score in the Full Analysis Set.

  Weeks 5, 9 and 15 (up to Day 107)

• The Changes From Baseline at Weeks 5, 9, 13 and 15 in the Severe Impairment Battery (SIB) Total Score for Subjects in the Mini Mental State Exam Version 2 (MMSE-2) 4-9 Stratification Group

  Weeks 5, 9, 13 and 15 (up to Day 107)

• The Changes From Baseline at Weeks 5, 9, 13 and 15 in the Severe Impairment Battery (SIB) Total Score for Subjects in the Mini Mental State Exam Version 2 (MMSE-2) 10-15 Stratification Group

  Weeks 5, 9, 13 and 15 (up tp Day 107)

• Individual Patient's Slope Over Time in SIB Total Score Evaluated Via Weeks 0, 5, 9, and 13

  Baseline through Week 13 (Day 91)

Study Arms (2)

Bryostatin 20µg

EXPERIMENTAL

20µg Bryostatin 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

Placebo

PLACEBO COMPARATOR

Placebo administered IV over 45 minutes every other weekafter 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.

Other: Placebo

Interventions

Bryostatin DRUG

The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.

Bryostatin 20µg

Placebo OTHER

The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the experimental drug

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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 dementia. The diagnosis must be confirmed at the time of the screening visit
• MMSE-2 score of 4-15 inclusive (applies to Screening Visit only)
• Patients must be able to perform at least one item on the SIB and may not have a SIB score \>93 at screening
• Neuroimaging computerized tomography (CT) or Magnetic Resonance Imaging (MRI) within the last 24 months consistent with a diagnosis of probable AD without any other clinically significant co-morbid pathologies. If there has been a significant change in the subject's clinical status since the last imaging study that is not consistent with progression of the subject's AD, an imaging study should be performed to confirm eligibility
• 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 and who will agree to accompany the subject to the clinic visits and reliably complete the caregiver questions
• Adequate vision and motor function to comply with testing
• If taking an approved cholinesterase inhibitor for treatment of Alzheimer's disease, 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 effect of the prescribed medication or a clinically significant change in the patient's status
• Subjects who are memantine naïve or have been off memantine for at least 30 days prior to initial treatment with study drug
• Subjects on neuroleptic medications must be on a stable dose for ≥4 weeks (dose adjustments will be permitted)
• Females participating in the study must meet one the following criteria:
• Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy or tubal ligation) for at least 6 months or postmenopausal (postmenopausal females must have no menstrual bleeding for at least 1 year) or
• If not postmenopausal, agree to use a double method of contraception, one of which is a barrier method (e.g., intrauterine device plus condom, spermicidal gel plus condom) 30 days prior to dosing until 30 days after last dose and have negative human chorionic gonadotropin (β-hCG) test for pregnancy at screening
• Males who have not had a vasectomy must use appropriate contraception methods (barrier or abstinence) from 30 days prior to dosing until 30 days after last dose

You may not qualify if:

• Dementia due to any condition other than AD, including vascular dementia (Rosen-Modified Hachinski Ischemic 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. . If there is a history of cancer the subject should be clear of cancer for at least 2 years prior to screening. More recent history of basal cell or squamous cell carcinoma and melanoma in situ (Stage 0) may be acceptable after review by the Medical Monitor.
• Creatinine clearance (CL) of \<45ml/min
• Poorly controlled diabetes, at the discretion of the Principal Investigator
• Concomitant treatment with NMDA receptor antagonists such as but not limited to memantine or drug combinations containing memantine, dextromethorphan (a cough suppressant), ketamine, phencyclidine (PCP), methoxetamine (MXE), nitrous oxide (N2O) and the following synthetic opioids: penthidine, levorphanol, methadone, dextropropoxyphene, tramadol, and ketobemidone.
• Use of vitamin E \> 400 International Units (IU) per day within 14 days prior to screening
• Use of valproic acid within 14 days prior to screening
• 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
• Any screening laboratory values outside the reference ranges that are deemed clinically significant by the PI
• Use of an investigational drug within 30 days prior to screening
• Suicidality defined as active suicidal thoughts during the 6 months prior to screening or at Baseline \[Type 4 or 5 on C-SSRS\], or history of suicide attempt in previous 2 years, or at serious suicide risk in PI's judgment

Sponsors & Collaborators

• Neurotrope Bioscience, Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (28)

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

Nader Pharmacology Research Institute

Los Alamitos, California, 90720, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Southern California Research, LLC

Simi Valley, California, 93065, United States

Location

JEM Research

Atlantis, Florida, 33462, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Alzheimer's Research and Treatment Center

Lake Worth, Florida, 33449, United States

Location

Miami Jewish Health / Stein Gerontological Institute

Miami, Florida, 33137, United States

Location

Phoenix Medical Research

Miami, Florida, 33165, United States

Location

Miami Dade Medical Research Institute, LLC

Miami, Florida, 33176, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Anchor Neuroscience

Pensacola, Florida, 32502, United States

Location

Stedman Clinical Trials

Tampa, Florida, 33613, United States

Location

Bioclinica Research

The Villages, Florida, 32162, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Medical Research & Health Education Foundation

Columbus, Georgia, 31909, United States

Location

Alexian Brothers Neuroscience Institute

Elk Grove Village, Illinois, 60007, United States

Location

Lake Charles Clinical Trials

Lake Charles, Louisiana, 70629, United States

Location

Alzheimer's Disease Center

Quincy, Massachusetts, 02169, United States

Location

Millennium Psychiatric Associates

Creve Coeur, Missouri, 63141, United States

Location

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, 07801, United States

Location

Neurological Associates of Albany, PC

Albany, New York, 12208, United States

Location

Burke Rehabilitation Hospital

White Plains, New York, 10605, United States

Location

Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Insight Clinical Trials, LLC

Shaker Heights, Ohio, 44122, United States

Location

Memory Health Center at Summit Research Network

Portland, Oregon, 97210, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Bryostatins

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Polyether Toxins; Polyether Polyketides; Ethers, Cyclic; Ethers; Organic Chemicals; Macrolides; Polyketides; Lactones; Macrocyclic Compounds; Polycyclic Compounds; Marine Toxins; Toxins, Biological; Biological Factors

Limitations and Caveats

An imbalance in the baseline Severe Impairment Battery (primary endpoint) was observed between the bryostatin treatment group and the placebo group, with the placebo group having an average SIB score higher than the treatment group.

Results Point of Contact

• Title: Alan J. Tuchman, MD, Acting Chief Medical Officer
• Organization: Neurotropebioscience, Inc

atuchman@neurotrope.com

973-242-0005

Study Officials

• Alan Tuchman, MD

  Neurotropebioscience, Inc

  STUDY DIRECTOR

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

Model Details: Eligible subjects will be stratified based on Mini Mental State Exam (MMSE-2) scores 4-9 vs. 10-15 and will be randomized 1:1 to one of two treatment arms: 20µg bryostatin or placebo for twelve weeks (7 doses).

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: June 18, 2018
• Study Start: June 20, 2018
• Primary Completion: July 25, 2019
• Study Completion: July 25, 2019
• Last Updated: October 1, 2020
• Results First Posted: October 1, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)