Bryostatin Treatment of Moderately Severe Alzheimer's Disease

Completed · Phase 2 · Has a placebo group

Conditions studied: Alzheimer Disease

In brief

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).

Key facts

Study ID

NCT04538066

Run by

Neurotrope Bioscience, Inc.

People needed

122

Starts

2020-08-30

Expected to finish

2022-11-16

Last updated by the study team

2024-07-31

Who can join

Age: 55 and older, up to 85. Sex: any. Healthy volunteers: not accepted.

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
• In the opinion of the PI subjects should be in reasonably good health over the last 6 months and any chronic disease should be stable -

You may not qualify if…

• Eligibility Criteria:
• Inclusion
• 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
• 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 13. 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 14. In the opinion of the PI subjects should be in reasonably good health over the last 6 months and any chronic disease should be stable Exclusion
• 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
• 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 90 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
• Major psychiatric illness such as current major depression according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition , current or past diagnosis of bipolar disorder, schizophrenia, or any other psychiatric disorder that might interfere with the assessments of safety or efficacy at the discretion of the PI
• Diagnosis of alcohol or drug abuse within the last 2 years
• Abnormal laboratory tests that suggest an alternate etiology for dementia. If the patient has prior history of serum B12 abnormality, anemia with hemoglobin ≤10g/dl, thyroid function abnormality, electrolyte abnormality, or positive syphilis serology the patient should be revaluated to determine if these potential causes of dementia have been addressed. Only if these causes have been ruled out as the cause of the dementia can the patient be enrolled.

Where it is running

• Axiom Research — Colton, California, United States
• Pacific Research Network — San Diego, California, United States
• JEM Research — Atlantis, Florida, United States
• Galiz Research — Hialeah, Florida, United States
• ClinCloud — Maitland, Florida, United States
• Miami Dade Medical Research Institute — Miami, Florida, United States
• Anchor Neuroscience — Pensacola, Florida, United States
• Progressive Medical Research — Port Orange, Florida, United States
• Alzheimer's Research and Treatment Center — Wellington, Florida, United States
• Atlanta Center for Medical Research — Atlanta, Georgia, United States
• Columbus Memory Center — Columbus, Georgia, United States
• iResearch Atlanta — Decatur, Georgia, United States
• iResearch Savannah — Savannah, Georgia, United States
• Fort Wayne Neurological Center — Fort Wayne, Indiana, United States
• Millenium Psychiatric Associates — St Louis, Missouri, United States
• Neurological Associates of Albany, P. C. — Albany, New York, United States
• Alzheimer's Research Center — Matthews, North Carolina, United States
• Summitt Research Network (Oregon) — Portland, Oregon, United States
• Kingfisher Cooperative — Spokane, Washington, United States

Full record on ClinicalTrials.gov

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