Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02221947
Recruitment Status : Terminated (Part 2 of study replaced by NTRP-101-202, assessing 3 doses of bryostatin.)
First Posted : August 21, 2014
Results First Posted : April 21, 2016
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Blanchette Rockefeller Neurosciences Insitute
Information provided by (Responsible Party):
Neurotrope Bioscience, Inc.

Brief Summary:
This study is being done to evaluate the safety, tolerability and potential effectiveness of a new investigational drug, bryostatin 1, in patients with Alzheimer's disease (AD).

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Bryostatin 1 Drug: Placebo Phase 1 Phase 2

Detailed Description:
This study is a single center, randomized, double-blind, placebo-controlled, parallel groups trial in patients with AD. Each subject enrolled in the trial will be randomized to receive a single IV dose of 0 (placebo) or 25 μg/m2 bryostatin. A total of 15 subjects (5 in the placebo arm and 10 in the treatment arm) will be enrolled in the study. The study consists of screening evaluations and on study evaluations divided into two segments, an inpatient segment and an outpatient segment. The four-day inpatient segment will consist of baseline evaluations and a 1-hour IV infusion of study drug followed by evaluations at multiple evaluations over the first 72 hrs post dose. During the outpatient segment, patients will be followed for AEs and have a final evaluation at 2 weeks post dose and a 4-week telephone safety follow up. Evaluations will include safety, efficacy, pharmacokinetics, and pharmacodynamics as assessed by PKC activity

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Preliminary Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Bryostatin 1 in Patients With Alzheimer's Disease
Study Start Date : June 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Bryostatin 1
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Drug: Bryostatin 1
25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.

Placebo Comparator: placebo
single dose of placebo, intravenous infusion over 1 hour
Drug: Placebo
Placebo, single dose via intravenous infusion over 1 hour.




Primary Outcome Measures :
  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Within 2 weeks of study drug dosing ]
    Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.

  2. Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD [ Time Frame: 48 hours post start of study drug infusion ]

    Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired.

    Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.



Secondary Outcome Measures :
  1. Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD [ Time Frame: Specified timepoints within 2 weeks post study drug infusion ]

    HVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired.

    Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired.

    Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired.

    Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.



Other Outcome Measures:
  1. Pharmacokinetic Parameters of Bryostatin. [ Time Frame: Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose. ]
    Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, age 50 - 85 yrs. Females are non-childbearing potential
  • Patient must have a cognitive deficit present for at least 1 year and meet diagnostic criteria for probable Alzheimer's Disease Dementia by NIA-AA criteria or prodromal Alzheimer's Disease
  • Mini Mental State Exam score of 16-26
  • Ability to walk, at least with an assistive device
  • Vision and hearing sufficient to comply with testing
  • Normal cognitive and social functioning prior to onset of dementia, with evidence of progressive symptoms from patient or informant
  • Consistent caregiver to accompany patient to visits
  • Sufficient basic education to be able to complete the cognitive assessments
  • Living outside an institution

Exclusion Criteria:

  • Dementia due to any condition other than AD, including vascular dementia
  • Significant neuroimaging abnormalities, previously known or discovered on screening MRI scan,
  • Evidence of clinically significant unstable cardiovascular, renal, hepatic, gastrointestinal, neurological, or metabolic disease within the past 6 months
  • Use of any drug within 14 days prior to randomization unless the dose of the drug and the condition being treated have been stable for at least 30 days and are expected to remain stable during the study
  • Use of tobacco products or nicotine-containing products within 3 months before Day 1
  • Use of high dose vitamin E, or valproic acid
  • Any medical or psychiatric condition that may require medication or surgical treatment during the study
  • Life expectancy less than 6 months
  • Use of an investigational drug within 2 months prior to the screening visit
  • Clinically significant neurological disease other than AD
  • Major depression, alcohol or drug dependence or suicidality
  • Psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2 weeks within the past 10 years, not linked to AD
  • Agitation sufficient to preclude participation in this trial
  • Epilepsy or anti-epileptic drug therapy
  • Abnormal laboratory tests that might point to another etiology for dementia;
  • Acute or poorly controlled medical illness
  • Likelihood, according to clinical judgment, of being transferred to a nursing home within 6 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02221947


Locations
Layout table for location information
United States, California
California Clinical Trials Medical Center
Glendale, California, United States, 91206
Sponsors and Collaborators
Neurotrope Bioscience, Inc.
Blanchette Rockefeller Neurosciences Insitute
Investigators
Layout table for investigator information
Principal Investigator: Hakop Gevorkyan, MD, MBA California Clinical Trials Medical Group
Layout table for additonal information
Responsible Party: Neurotrope Bioscience, Inc.
ClinicalTrials.gov Identifier: NCT02221947    
Other Study ID Numbers: NTRP101-201
First Posted: August 21, 2014    Key Record Dates
Results First Posted: April 21, 2016
Last Update Posted: November 6, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Neurotrope Bioscience, Inc.:
Alzheimer's
bryostatin
PKC epsilon
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Bryostatin 1
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents