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Alzheimer DiseasePhase 2NCT04538066

Bryostatin Treatment of Moderately Severe Alzheimer's Disease

A Phase 2 study testing Bryostatin 1 in people with Alzheimer Disease, run by Neurotrope Bioscience, Inc. at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 55 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
Bryostatin 1
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
122 participants
Where
19 sitesUnited States
Study dates
30 Aug 2020to 16 Nov 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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 -
  • 1. 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.
  • History of prolonged QT or prolonged QT on screening ECG (QTcB or QTcF >499 per central reader)
  • Acute or poorly controlled medical illness: blood pressure > 180 mmHg systolic or 100 mmHg diastolic; myocardial infarction within 6 months; uncompensated congestive heart failure [New York Heart Association (NYHA) Class III or IV]
  • Known to be seropositive for human immunodeficiency virus (HIV)
  • Known to be seropositive for Hepatitis B or C, unless successful curative treatment for Hepatitis C (e.g., Harvoni) has been received and there is documentation that there is no Hep B/C virus detected 3 months after completion of treatment
  • AST or ALT >3x upper limit of normal (ULN) and total bilirubin >2x ULN or International Normalized Ratio (INR) >1.5
  • Prior exposure to bryostatin, or known sensitivity to bryostatin or any ingredient in the study drug
  • Any other concurrent medical condition, which in the opinion of the PI makes the subject unsuitable for the clinical study -

Who cannot join

  • Eligibility Criteria:

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • Neurological Associates of Albany, P. C.

    Albany, New York, 12208

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • JEM Research

    Atlantis, Florida, 33462

  • Axiom Research

    Colton, California, 92324

  • Columbus Memory Center

    Columbus, Georgia, 31909

  • iResearch Atlanta

    Decatur, Georgia, 30030

  • Fort Wayne Neurological Center

    Fort Wayne, Indiana, 46804

  • Galiz Research

    Hialeah, Florida, 33016

  • ClinCloud

    Maitland, Florida, 32751

  • Alzheimer's Research Center

    Matthews, North Carolina, 28105

  • Miami Dade Medical Research Institute

    Miami, Florida, 33176

  • Anchor Neuroscience

    Pensacola, Florida, 32502

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Summitt Research Network (Oregon)

    Portland, Oregon, 97210

  • Pacific Research Network

    San Diego, California, 92103

  • iResearch Savannah

    Savannah, Georgia, 31405

  • Kingfisher Cooperative

    Spokane, Washington, 99202

  • Millenium Psychiatric Associates

    St Louis, Missouri, 63132

  • Alzheimer's Research and Treatment Center

    Wellington, Florida, 33414

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing Safety, Tolerability and Long-term Efficacy of Bryostatin in the Treatment of Moderately Severe Alzheimer's Disease Subjects Not Receiving Memantine Treatment

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).

Read the detailed description

This is a randomized double-blind placebo-controlled, Phase 2 study comparing bryostatin-1 to placebo for long-term efficacy in the treatment of moderately severe AD (Mini Mental State Examination, 2nd edition scores of 10-18 at baseline) in the absence of memantine. Eligible subjects will receive 7 doses of bryostatin (i.v., 20μg) or matching placebo during the first 12 weeks. A second course of treatment consisting of 7 doses will begin 30 days after the final dose of the first treatment period. Cognitive tests will be assessed at intervals during the study and 4 months after the final dose of study drug. The primary endpoint is the total SIB score assessment obtained at Week 28, following completion of 2 courses of treatment.

Being tested
Bryostatin 1, Placebo
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bryostatin 1Drug

    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.

  • PlaceboOther

    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.

Study groups in NCT04538066
Study groupRoleWhat they receive
Bryostatin 1Active comparator20ug 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.
Receives: Drug: Bryostatin 1
PlaceboPlacebo comparatorPlacebo 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.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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.

  2. 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.

    Measured: Primary efficacy analysis at Week 28

Secondary outcomes (5)

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

    The SIB assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.

    Measured: 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.

  2. The SIB Total Score From Baseline at Week 13

    The SIB assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.

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

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

    The Severe Impaorment Battery (SIB) assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.

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

  4. 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

    MMSE-2 tests selected aspects of cognition on a scale of 0-30. Subjects with MMSE-2 scores of 10-18 will be enrolled in the study. Scores of 10-14 indicate greater impairment than scores of 15-18. Analyses were done comparing all subjects treated with either bryostatin or placebo, and additionally, comparing subjects grouped by MMSE-2 scores of 10-14 and 15-18 treated with either bryostatin or placebo.

    Measured: Weeks 9, 20, 24 and 30

  5. SIB Trends Over Time

    Individual-specific slopes of total Severe Impairment Battery (SIB) scores will be obtained for all patients. Scores range from 0-100, lower scores indicate greater impairment.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2020
  2. Study start30 Aug 2020
  3. Primary completion16 Nov 2022
  4. Study completion16 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Study subjects will be randomized 1:1 to receive either the active treatment, bryostatin-1, or placebo.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
122 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04538066
Sponsor's protocol ID
NTRP101-204
Other IDs
R44AG066366
Status last verified
Apr 2024
First submitted
6 Aug 2020
Last updated
31 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bryostatin 1 in people with Alzheimer Disease, run by Neurotrope Bioscience, Inc. at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety: Treatment-emergent Adverse Events and Serious Adverse Events for All Randomized Subjects Who Received Any Study Medication (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04538066.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2024.

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