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

• ClinicalTrials.gov Identifier: NCT02221947
• Recruitment Status: Terminated
• First Posted: August 21, 2014
• Results First Posted: April 21, 2016
• Last Update Posted: November 6, 2017
• Sponsor: Neurotrope Bioscience, Inc.
• Collaborator: Blanchette Rockefeller Neurosciences Insitute
• Information provided by (Responsible Party): Neurotrope Bioscience, Inc.

Study Description

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

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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).

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, California

California Clinical Trials Medical Center

Glendale, California, United States, 91206

Sponsors and Collaborators

Neurotrope Bioscience, Inc.

Blanchette Rockefeller Neurosciences Insitute

Investigators

• Principal Investigator: Hakop Gevorkyan, MD, MBA; California Clinical Trials Medical Group

More Information

• Responsible Party: Neurotrope Bioscience, Inc.
• ClinicalTrials.gov Identifier: NCT02221947
• Other Study ID Numbers: NTRP101-201
• First Posted: August 21, 2014
• 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:

Bryostatin 1; Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents