Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bryostatin 1
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's, bryostatin, PKC epsilon
Eligibility 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
Sites / Locations
- California Clinical Trials Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Bryostatin 1
placebo
Arm Description
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
single dose of placebo, intravenous infusion over 1 hour
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
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.
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
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
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
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.
Full Information
NCT ID
NCT02221947
First Posted
July 2, 2014
Last Updated
October 3, 2017
Sponsor
Neurotrope Bioscience, Inc.
Collaborators
Blanchette Rockefeller Neurosciences Insitute
1. Study Identification
Unique Protocol Identification Number
NCT02221947
Brief Title
Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease
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 Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Why Stopped
Part 2 of study replaced by NTRP-101-202, assessing 3 doses of bryostatin.
Study Start Date
June 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurotrope Bioscience, Inc.
Collaborators
Blanchette Rockefeller Neurosciences Insitute
4. Oversight
Data Monitoring Committee
No
5. 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).
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's, bryostatin, PKC epsilon
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bryostatin 1
Arm Type
Active Comparator
Arm Description
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
single dose of placebo, intravenous infusion over 1 hour
Intervention Type
Drug
Intervention Name(s)
Bryostatin 1
Intervention Description
25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, single dose via intravenous infusion over 1 hour.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description
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.
Time Frame
Within 2 weeks of study drug dosing
Title
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Description
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.
Time Frame
48 hours post start of study drug infusion
Secondary Outcome Measure Information:
Title
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Description
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.
Time Frame
Specified timepoints within 2 weeks post study drug infusion
Other Pre-specified Outcome Measures:
Title
Pharmacokinetic Parameters of Bryostatin.
Description
Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).
Time Frame
Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hakop Gevorkyan, MD, MBA
Organizational Affiliation
California Clinical Trials Medical Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
California Clinical Trials Medical Center
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease
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