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CompletedPhase 2Results posted
A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease
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
Lead sponsor
Asset
Bryostatin 1
Listed sites
29
Recruiting sites
-
Enrollment
147
actual
Study population
Alzheimer’s disease
Key I/E criteria
•Alzheimer's disease•MMSE 4-15•Study partner/caregiver required•Background AD symptomatic therapy, if used: stable ≥3 months
Primary endpoints
•Safety•Efficacy
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
NCT IDNCT02431468
Org study IDNTRP-101-202
Timeline
Milestones
Study first posted2015-05-01estimated
Study start2015-11 (month precision)
Primary completion2017-02actual (month precision)
Study completion2017-02actual (month precision)
Last update posted2018-07-06actual
Results first posted2018-07-06actual
Assets
Drug assets
Study populations
Who this study enrolls
Alzheimer’s disease
Eligibility
Who can enroll
Minimum age55 Years
Maximum age85 Years
SexAll
Healthy volunteersNot accepted
Inclusion criteria
•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
•Mini Mental State Exam (MMSE-2) score of 4-15
•Patients must be able to perform at least one item on the Severe Impairment Battery Scale
•Neuroimaging (computerized tomography (CT) or Magnetic Resonance Imaging (MRI)) within the last 24 months consistent with a diagnosis of probable Alzheimer's disease (AD)
•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
•Adequate vision and motor function to comply with testing
•If taking drugs approved for treatment of Alzheimer's disease (e.g. cholinesterase inhibitors, memantine), 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 event or a clinically significant change in the patient's status
Exclusion criteria
•Dementia due to any condition other than AD, including vascular dementia (Rosen-modified Hachinski lschemic 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
•Poorly controlled diabetes, at the discretion of the Principal Investigator
•Creatinine clearance (CL) of <45ml/min
•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
•Use of an investigational drug within 30 days prior to screening
•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
Endpoints (7)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Global cognition
5
Safety / tolerability / PK
2
Global cognition
5 endpointsPrimary/protocol endpoint
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS)
Time frame:Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107)
change from baseline, improvement
Primary/registry result
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS)
Time frame:Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107)
change from baseline, improvement
Posted result
| Group | Value (mean), mean change from baseline in SIB score | Standard deviation |
|---|---|---|
| Bryostatin 1 20ugWeek 13 Full Analysis Set (FAS)n=38 Participants | 1.6 | 7.10 |
| Week 13 Completer Analysis Set (CAS)n=38 Participants | 1.6 | 7.10 |
| 30-Day Followup Full Analysis Setn=27 Participants | 2.3 | 8.17 |
| 30-Day Followup Completer Analysis Setn=27 Participants | 2.3 | 8.17 |
| Bryostatin 1 40ugWeek 13 Full Analysis Set (FAS)n=33 Participants | 0.8 | 6.58 |
| Week 13 Completer Analysis Set (CAS)n=33 Participants | 0.8 | 6.58 |
| 30-Day Followup Full Analysis Setn=22 Participants | 0.6 | 7.51 |
| 30-Day Followup Completer Analysis Setn=20 Participants | 0.9 | 7.85 |
| PlaceboWeek 13 Full Analysis Set (FAS)n=42 Participants | -0.4 | 9.02 |
| Week 13 Completer Analysis Set (CAS)n=42 Participants | -0.7 | 9.02 |
| 30-Day Followup Full Analysis Setn=29 Participants | -2.7 | 11.44 |
| 30-Day Followup Completer Analysis Setn=29 Participants | -2.7 | 11.44 |
Mean Difference (Net)6.5p<0.1t-test, 1 sided
Mean Difference (Net)6.5p<0.1t-test, 1 sided
Change from baseline in SIB in the Completer Analysis Set (CAS)
Secondary/protocol endpoint
Secondary Efficacy Endpoints
Time frame:Week 5, Week 9, Week 13
Mini-Mental State Examination (MMSE)
change from baseline, improvement
Secondary/registry result
Secondary Efficacy Endpoints
Time frame:Week 5, Week 9, Week 13
Mini-Mental State Examination (MMSE)
change from baseline, improvement
Posted result
| Group | Value (mean), mean change from baseline | Standard deviation |
|---|---|---|
| Bryostatin 1 20ugSIB Week 5 Full Analysis Setn=44 Participants | 1.5 | 7.36 |
| SIB Week 5 Completer Analysis Setn=38 Participants | 1.7 | 6.02 |
| SIB Week 9 Full Analysis Setn=38 Participants | 1.3 | 6.87 |
| SIB Week 9 Completer Analysis Setn=37 Participants | 1.2 | 6.93 |
| Week 5 ADCS-ADL-SIV : FASn=43 Participants | -0.3 | 4.16 |
| Week 9 ADCS-ADL-SIV : FASn=37 Participants | -1.4 | 4.68 |
| Week 13 ADCS-ADL-SIV : FASn=37 Participants | -0.7 | 4.59 |
| Week 5 MMSE-2: FASn=44 Participants | 0.4 | 2.43 |
| Week 9 MMSE-2: FASn=38 Participants | 0.8 | 2.98 |
| Week 13 MMSE-2: FASn=38 Participants | 0.5 | 3.09 |
| Week 5 Neuropsychiatric Inventory (NPI): FASn=41 Participants | -0.5 | 11.72 |
| Week 9 Neuropsychiatric Inventory (NPI): FASn=37 Participants | 0.5 | 11.97 |
| Week 13 Neuropsychiatric Inventory (NPI): FASn=37 Participants | 1.0 | 12.62 |
| Bryostatin 1 40ugSIB Week 5 Full Analysis Setn=44 Participants | -0.8 | 6.55 |
| SIB Week 5 Completer Analysis Setn=32 Participants | 0.1 | 5.93 |
| SIB Week 9 Full Analysis Setn=38 Participants | -0.2 | 6.41 |
| SIB Week 9 Completer Analysis Setn=33 Participants | -0.1 | 6.06 |
| Week 5 ADCS-ADL-SIV : FASn=43 Participants | -1.1 | 6.31 |
| Week 9 ADCS-ADL-SIV : FASn=38 Participants | -1.5 | 5.05 |
| Week 13 ADCS-ADL-SIV : FASn=33 Participants | -1.0 | 4.86 |
| Week 5 MMSE-2: FASn=44 Participants | -0.1 | 2.79 |
| Week 9 MMSE-2: FASn=38 Participants | 0.3 | 3.01 |
| Week 13 MMSE-2: FASn=33 Participants | 0.3 | 2.54 |
| Week 5 Neuropsychiatric Inventory (NPI): FASn=41 Participants | 1.7 | 12.03 |
| Week 9 Neuropsychiatric Inventory (NPI): FASn=34 Participants | 2.0 | 8.33 |
| Week 13 Neuropsychiatric Inventory (NPI): FASn=32 Participants | 2.0 | 11.94 |
| PlaceboSIB Week 5 Full Analysis Setn=46 Participants | -1.2 | 10.31 |
| SIB Week 5 Completer Analysis Setn=42 Participants | -1.9 | 10.33 |
| SIB Week 9 Full Analysis Setn=43 Participants | -0.0 | 9.91 |
| SIB Week 9 Completer Analysis Setn=42 Participants | -0.1 | 10.0 |
| Week 5 ADCS-ADL-SIV : FASn=48 Participants | -0.7 | 5.07 |
| Week 9 ADCS-ADL-SIV : FASn=43 Participants | -1.3 | 4.07 |
| Week 13 ADCS-ADL-SIV : FASn=42 Participants | -2.2 | 5.28 |
| Week 5 MMSE-2: FASn=46 Participants | -0.1 | 2.40 |
| Week 9 MMSE-2: FASn=43 Participants | 0.5 | 3.11 |
| Week 13 MMSE-2: FASn=42 Participants | -0.2 | 3.49 |
| Week 5 Neuropsychiatric Inventory (NPI): FASn=44 Participants | -2.4 | 10.31 |
| Week 9 Neuropsychiatric Inventory (NPI): FASn=41 Participants | -2.5 | 11.05 |
| Week 13 Neuropsychiatric Inventory (NPI): FASn=39 Participants | 1.0 | 10.45 |
Post_hoc/registry result
Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline
Time frame:Assessments at weeks 5, 9, 13, and 30 days after end of treatment (up to day 107).
change from baseline, improvement
Posted result
| Group | Value (mean), mean change from baseline in SIB score | Standard deviation |
|---|---|---|
| Bryostatin 1 20ug With MemantineWeek 5 SIB change from Baselinen=26 Participants | 0.1 | 8.11 |
| Week 9 SIB change from Baselinen=23 Participants | -0.1 | 6.52 |
| Week 13 SIB change from Baselinen=22 Participants | -0.5 | 6.51 |
| 30-day Followup SIB change from Baselinen=15 Participants | -1.1 | 8.39 |
| Bryostatin 1 40ug With MemantineWeek 5 SIB change from Baselinen=37 Participants | -1.6 | 6.50 |
| Week 9 SIB change from Baselinen=31 Participants | -0.6 | 6.88 |
| Week 13 SIB change from Baselinen=26 Participants | -0.1 | 6.61 |
| 30-day Followup SIB change from Baselinen=20 Participants | 0.3 | 7.71 |
| Placebo With MemantineWeek 5 SIB change from Baselinen=31 Participants | -1.3 | 10.50 |
| Week 9 SIB change from Baselinen=29 Participants | -0.4 | 11.01 |
| Week 13 SIB change from Baselinen=28 Participants | -0.5 | 10.03 |
| 30-day Followup SIB change from Baselinen=18 Participants | -3.8 | 13.10 |
| Bryostatin 1 20ug Without MemantineWeek 5 SIB change from Baselinen=18 Participants | 3.4 | 5.75 |
| Week 9 SIB change from Baselinen=15 Participants | 3.5 | 7.04 |
| Week 13 SIB change from Baselinen=16 Participants | 4.5 | 7.01 |
| 30-day Followup SIB change from Baselinen=12 Participants | 6.7 | 5.58 |
| Bryostatin 1 40ug Without MemantineWeek 5 SIB change from Baselinen=7 Participants | 3.9 | 4.98 |
| Week 9 SIB change from Baselinen=7 Participants | 2.0 | 3.16 |
| Week 13 SIB change from Baselinen=7 Participants | 3.9 | 5.84 |
| 30-day Followup SIB change from Baselinen=2 Participants | 4.0 | 5.66 |
| Placebo Without MemantineWeek 5 SIB change from Baselinen=15 Participants | -1.2 | 10.26 |
| Week 9 SIB change from Baselinen=15 Participants | 0.8 | 7.44 |
| Week 13 SIB change from Baselinen=14 Participants | -1.1 | 6.89 |
| 30-day Followup SIB change from Baselinen=11 Participants | -1.0 | 8.31 |
Safety / tolerability / PK
2 endpointsPrimary/protocol endpoint
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events
Time frame:Baseline through 30 days post end of treatment (up to Day 107)
event count, event
Primary/registry result
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events
Time frame:Baseline through 30 days post end of treatment (up to Day 107)
event count, event
Posted result
| Group | Value (number), participants | Reported bounds |
|---|---|---|
| Bryostatin 1 20ugNumber of Subjects w Treatment Emergent AE (TEAE)n=46 Participants | 30 | - |
| # of Subjects w Treatment Related TEAEn=46 Participants | 17 | - |
| # of Subjects w TEAE leading to treatment discont.n=46 Participants | 1 | - |
| # of Subjects with Serious TEAEn=46 Participants | 1 | - |
| # of Subjects with Treatment Related Serious TEAEn=46 Participants | 1 | - |
| # of Subjects w Treatment Emergent Myalgian=46 Participants | 1 | - |
| # of Subjects w Serious Treatment Emergent Myalgian=46 Participants | 0 | - |
| # of Subjects with Fatal TEAEn=46 Participants | 0 | - |
| Bryostatin 1 40ugNumber of Subjects w Treatment Emergent AE (TEAE)n=47 Participants | 39 | - |
| # of Subjects w Treatment Related TEAEn=47 Participants | 24 | - |
| # of Subjects w TEAE leading to treatment discont.n=47 Participants | 3 | - |
| # of Subjects with Serious TEAEn=47 Participants | 6 | - |
| # of Subjects with Treatment Related Serious TEAEn=47 Participants | 4 | - |
| # of Subjects w Treatment Emergent Myalgian=47 Participants | 4 | - |
| # of Subjects w Serious Treatment Emergent Myalgian=47 Participants | 0 | - |
| # of Subjects with Fatal TEAEn=47 Participants | 1 | - |
| PlaceboNumber of Subjects w Treatment Emergent AE (TEAE)n=48 Participants | 28 | - |
| # of Subjects w Treatment Related TEAEn=48 Participants | 8 | - |
| # of Subjects w TEAE leading to treatment discont.n=48 Participants | 2 | - |
| # of Subjects with Serious TEAEn=48 Participants | 3 | - |
| # of Subjects with Treatment Related Serious TEAEn=48 Participants | 0 | - |
| # of Subjects w Treatment Emergent Myalgian=48 Participants | 0 | - |
| # of Subjects w Serious Treatment Emergent Myalgian=48 Participants | 0 | - |
| # of Subjects with Fatal TEAEn=48 Participants | 0 | - |
Provenance
Sources
Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableClinicalTrials.gov results section
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.