Bryostatin Treatment of Moderately Severe Alzheimer's Disease

NCT04538066 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: NTRP101-204R44AG066366
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 19

Brief Summary

To evaluate the safety, tolerability, and long-term efficacy of bryostatin 1 (hereafter referred to as bryostatin) for the treatment of moderately severe Alzheimer's disease (AD).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Safety: Treatment-emergent Adverse Events and Serious Adverse Events for All Randomized Subjects Who Received Any Study Medication

  Treatment emergent adverse events and serious adverse events will be analyzed by treatment group.

  Prior to version 6 of the protocol, final assessments were performed at Week 42, 12 weeks after the last study treatment. The final study visit took place at Week 30 for subjects remaining in the study after the protocol amendment.

• Efficacy: Severe Impairment Battery Total Score Assessment Obtained After Completion of the Second Couse of Treatment (Week 28)

  The treatment difference in the primary efficacy endpoint of Severe Impairment Battery (SIB). 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 efficacy analysis at Week 28

Secondary Outcomes (5)

• Severe Impairment Battery (SIB) Total Score at the End of the Week 42 Follow-up Visit

  Week 42 was the final follow-up for study subjects, occurring 16 weeks after the last dose of study drug. Subjects who remained in the study at the time version 6 of the protocol was implemented did not have Week 42 visit.

• The SIB Total Score From Baseline at Week 13

  Week 13 followed the first 12-week course of study treatment.

• The Changes From Baseline in SIB Total Scores at Weeks 9, 20, 24, and 30

  Weeks 9, 20 and 24 occur during the treatment phase of the study. Week 30 occurred 4 weeks after end of treatment.

• SIB Total Scores From Baseline at Weeks 9, 20, 24 and 30 for Subjects With Baseline Mini Mental State Exam Version 2 (MMSE-2) Scores of 10-14 and 15-18

  Weeks 9, 20, 24 and 30

• SIB Trends Over Time

  Slopes will be estimated by using SIB data at Week 0, 5, 9, 13, 15, 20, 24, and 28

Study Arms (2)

Bryostatin 1

ACTIVE COMPARATOR

20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period.

Drug: Bryostatin 1

Placebo

PLACEBO COMPARATOR

Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period.

Other: Placebo

Interventions

Bryostatin 1 DRUG

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, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.

Bryostatin 1

Placebo OTHER

Placebo 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, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.

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 10-18 inclusive (applies to Screening Visit only)
• Patients must have a baseline SIB total score of at least 60 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 90 days prior to initial treatment with study drug
• Subjects on neuroleptic medications must be on a stable dose for ≥4 weeks at screening (dose adjustments will be permitted if medically necessary at the discretion of the PI)
• 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:

• Eligibility Criteria:
• \. Written informed consent from caregiver and subject (if possible) or legally acceptable representative if different from caregiver 2. Male and female subjects 55-85 years of age inclusive 3. 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 4. MMSE-2 score of 10-18 inclusive (applies to Screening Visit only) 5. Patients must have a baseline SIB total score of at least 60 and may not have a SIB score \>93 at screening 6. 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 7. 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 8. Adequate vision and motor function to comply with testing 9. 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 10. Subjects who are memantine naïve or have been off memantine for at least 90 days prior to initial treatment with study drug 11. Subjects on neuroleptic medications must be on a stable dose for ≥4 weeks at screening (dose adjustments will be permitted if medically necessary at the discretion of the PI) 12. 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
• 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, dextrpropoxyphene, tramadol, and ketobemidone.
• Use of vitamin E \> 400 International Units (IU) per day within 14 days prior to screening
• Use of acetaminophen within 14 days prior to screening
• Use of gabapentin 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

Sponsors & Collaborators

• Neurotrope Bioscience, Inc.: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (19)

Axiom Research

Colton, California, 92324, United States

Location

Pacific Research Network

San Diego, California, 92103, United States

Location

JEM Research

Atlantis, Florida, 33462, United States

Location

Galiz Research

Hialeah, Florida, 33016, United States

Location

ClinCloud

Maitland, Florida, 32751, United States

Location

Miami Dade Medical Research Institute

Miami, Florida, 33176, United States

Location

Anchor Neuroscience

Pensacola, Florida, 32502, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Columbus Memory Center

Columbus, Georgia, 31909, United States

Location

iResearch Atlanta

Decatur, Georgia, 30030, United States

Location

iResearch Savannah

Savannah, Georgia, 31405, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46804, United States

Location

Millenium Psychiatric Associates

St Louis, Missouri, 63132, United States

Location

Neurological Associates of Albany, P. C.

Albany, New York, 12208, United States

Location

Alzheimer's Research Center

Matthews, North Carolina, 28105, United States

Location

Summitt Research Network (Oregon)

Portland, Oregon, 97210, United States

Location

Kingfisher Cooperative

Spokane, Washington, 99202, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

bryostatin 1

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Synaptogenix, Inc.

atuchman@synaptogen.com

973 242-0005

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor, investigators and staff, and the clinical research organization are all blinded to study treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study subjects will be randomized 1:1 to receive either the active treatment, bryostatin-1, or placebo.

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: September 3, 2020
• Study Start: August 30, 2020
• Primary Completion: November 16, 2022
• Study Completion: November 16, 2022
• Last Updated: July 31, 2024
• Results First Posted: July 31, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)