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Alzheimer DiseasePhase 2NCT03560245

A Study of Bryostatin in Moderately Severe to Severe Alzheimer's Disease Subjects Not On Memantine

A Phase 2 study testing Bryostatin in people with Alzheimer Disease, run by Neurotrope Bioscience, Inc. at 28 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

This is a randomized double-blind Placebo-controlled, Phase 2 study comparing bryostatin to placebo for the treatment of moderately severe to severe Alzheimer's disease in subjects not receiving memantine treatment. 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
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
108 participants
Where
28 sitesUnited States
Study dates
20 Jun 2018to 25 Jul 2019
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 4-15 inclusive (applies to Screening Visit only)
  • Patients must be able to perform at least one item on the SIB 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 30 days prior to initial treatment with study drug
  • Subjects on neuroleptic medications must be on a stable dose for ≥4 weeks (dose adjustments will be permitted)
  • 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 -

Who cannot join

  • 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
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  • 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, dextropropoxyphene, tramadol, and ketobemidone.
  • Use of vitamin E > 400 International Units (IU) per day 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 30 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

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

United States28 sites

  • Neurological Associates of Albany, PC

    Albany, New York, 12208

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • JEM Research

    Atlantis, Florida, 33462

  • Alzheimer's Memory Center

    Charlotte, North Carolina, 28270

  • Medical Research & Health Education Foundation

    Columbus, Georgia, 31909

  • Millennium Psychiatric Associates

    Creve Coeur, Missouri, 63141

  • Brain Matters Research

    Delray Beach, Florida, 33445

  • Alexian Brothers Neuroscience Institute

    Elk Grove Village, Illinois, 60007

  • Neuro Pain Medical Center

    Fresno, California, 93710

  • MD Clinical

    Hallandale, Florida, 33009

  • Lake Charles Clinical Trials

    Lake Charles, Louisiana, 70629

  • Alzheimer's Research and Treatment Center

    Lake Worth, Florida, 33449

  • Nader Pharmacology Research Institute

    Los Alamitos, California, 90720

  • Miami Jewish Health / Stein Gerontological Institute

    Miami, Florida, 33137

  • Phoenix Medical Research

    Miami, Florida, 33165

  • Miami Dade Medical Research Institute, LLC

    Miami, Florida, 33176

  • Medical Research Group of Central Florida

    Orange City, Florida, 32763

  • Bioclinica Research

    Orlando, Florida, 32806

  • Anchor Neuroscience

    Pensacola, Florida, 32502

  • Memory Health Center at Summit Research Network

    Portland, Oregon, 97210

  • Alzheimer's Disease Center

    Quincy, Massachusetts, 02169

  • Syrentis Clinical Research

    Santa Ana, California, 92705

  • Insight Clinical Trials, LLC

    Shaker Heights, Ohio, 44122

  • Southern California Research, LLC

    Simi Valley, California, 93065

  • The Cognitive and Research Center of New Jersey

    Springfield, New Jersey, 07801

  • Stedman Clinical Trials

    Tampa, Florida, 33613

  • Bioclinica Research

    The Villages, Florida, 32162

  • Burke Rehabilitation Hospital

    White Plains, New York, 10605

Other trials in United States

About this study

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

This is a randomized double-blind Placebo-controlled, Phase 2 study comparing bryostatin to placebo for the treatment of moderately severe to severe Alzheimer's disease in subjects not receiving memantine treatment. The study is 15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose of study drug. Subjects will receive 7 doses of study drug during the study. The primary efficacy endpoint is defined as the change from baseline to Week 13 in the Severe Impairment Battery (SIB) total score.

Read the detailed description

Eligible subjects will be stratified based on Mini Mental State Exam (MMSE-2) scores 4-9 vs. 10-15 and will be randomized 1:1 to one of two treatment arms: 20µg bryostatin or placebo for twelve weeks. The first two doses of study drug will be a loading dose 20% higher (i.e., 24µg) than the assigned dose and will be administered one week apart. Thereafter, the assigned dose of 20µg will commence with the third dose and be administered every other week. Drug is administered IV by continuous infusion over 45(±5) minutes. Subjects are scheduled to receive seven doses over 12 weeks.

Being tested
Bryostatin, 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.

  • BryostatinDrug

    The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.

  • PlaceboOther

    The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the experimental drug

Study groups in NCT03560245
Study groupRoleWhat they receive
Bryostatin 20µgExperimental20µg Bryostatin 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.
Receives: Drug: Bryostatin
PlaceboPlacebo comparatorPlacebo administered IV over 45 minutes every other weekafter 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
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 (AEs) and Serious Adverse Events (SAEs)

    Incidence of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia

    Measured: Baseline through 30 days post end of treatment (up to Day 107)

  2. Efficacy: The Primary Efficacy Endpoint is Defined as the Change From Baseline to Week 13 in the Severe Impairment Battery (SIB) Total Score in the Full Analysis Set

    The Severe Impairment Battery (SIB) assesses cognition in subjects with moderate and severe Alzheimer's disease(AD). Test questions measure 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 total point score range of 0-100. Lower scores indicate greater cognitive impairment.

    Measured: The change in the SIB Total Score from baseline to Week 13 (Day 91)

Secondary outcomes (4)

  1. The Changes From Baseline at Weeks 5, 9 and 15 in the Severe Impairment Battery (SIB) Total Score in the Full Analysis Set.

    The Severe Impairment Battery (SIB) assesses cognition in subjects with Alzheimer's disease. SIB scores at Weeks 5, 9 and the Week 15 follow-up visit will be assessed. Test questions measure 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 total point score range of 0-100. Lower scores indicate greater cognitive impairment.

    Measured: Weeks 5, 9 and 15 (up to Day 107)

  2. The Changes From Baseline at Weeks 5, 9, 13 and 15 in the Severe Impairment Battery (SIB) Total Score for Subjects in the Mini Mental State Exam Version 2 (MMSE-2) 4-9 Stratification Group

    The SIB is used to assess cognition in subjects with moderate and severe AD and is a useful outcome measure in advanced stages of disease. 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: Weeks 5, 9, 13 and 15 (up to Day 107)

  3. The Changes From Baseline at Weeks 5, 9, 13 and 15 in the Severe Impairment Battery (SIB) Total Score for Subjects in the Mini Mental State Exam Version 2 (MMSE-2) 10-15 Stratification Group

    Mini Mental State Exam version 2 (MMSE-2) scores between 10 and 15 are representative of moderately severe Alzheimer's disease. The SIB is used to assess cognition in subjects with moderate and severe AD and is a useful outcome measure in advanced stages of disease. 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: Weeks 5, 9, 13 and 15 (up tp Day 107)

  4. Individual Patient's Slope Over Time in SIB Total Score Evaluated Via Weeks 0, 5, 9, and 13

    Severe Impairment Battery (SIB) trend analyses will be assessed for individual patients. SIB scores were evaluated in subjects at various time points during the study. Individual-specific SIB slopes were estimated for all patients over each person's available SIB outcome measures.

    Measured: Baseline through Week 13 (Day 91)

Timeline

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

  1. First posted18 Jun 2018
  2. Study start20 Jun 2018
  3. Primary completion25 Jul 2019
  4. Study completion25 Jul 2019

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
Eligible subjects will be stratified based on Mini Mental State Exam (MMSE-2) scores 4-9 vs. 10-15 and will be randomized 1:1 to one of two treatment arms: 20µg bryostatin or placebo for twelve weeks (7 doses).
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03560245
Sponsor's protocol ID
NTRP101-203
Status last verified
Jun 2020
First submitted
6 Jun 2018
Last updated
1 Oct 2020
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 in people with Alzheimer Disease, run by Neurotrope Bioscience, Inc. at 28 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 16 inclusion and 25 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 1 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 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 1 Oct 2020). 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 (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline through 30 days post end of treatment (up to Day 107)). 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 NCT03560245.

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 1 Oct 2020.

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