Dataset Information

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

ABSTRACT:

Background

Bryostatin-activated PKC epsilon pre-clinically induces synaptogenesis, anti-apoptosis, anti-amyloid-β oligomers, and anti-hyperphosphorylated tau.

Objectives

To investigate bryostatin safety, tolerability, and efficacy to improve cognition in advanced Alzheimer's disease (AD) patients.

Methods

A double-blind, randomized, placebo-controlled Phase II, 12-week trial of i.v. bryostatin for 150 advanced AD patients (55-85) with MMSE-2 of 4-15, randomized 1:1:1 into 20 μg and 40 μg bryostatin, and placebo arms. The Full Analysis Set (FAS) and the Completer Analysis Set (CAS) were pre-specified alternative assessments (1-sided, p < 0.1 for primary efficacy, and 2-sided, p < 0.05 for pre-specified and post hoc exploratory analyses).

Results

The safety profile was similar for 20 μg treatment and placebo patients. The 40 μg patients showed safety and drop-out issues, but no efficacy. Primary improvement of Severe Impairment Battery (SIB) scores at 13 weeks was not significant (p = 0.134) in the FAS, although in the CAS, the SIB comparison favored 20 μg bryostatin compared to placebo patients (p < 0.07). Secondary analyses at weeks 5 and 15 (i.e., 30 days post-final dosing) also favored 20 μg bryostatin compared to placebo patients. A pre-specified ANCOVA for baseline memantine blocking bryostatin and positive post-hoc trend analyses were statistically significant (2-sided, p < 0.05).

Conclusion

Although the primary endpoint was not significant in the FAS, primary and secondary analyses in the CAS, and pre-specified and post-hoc exploratory analyses did favor bryostatin 20 μg compared to the placebo cohort. These promising Phase II results support further trials of 20 μg bryostatin- without memantine- to treat AD.

SUBMITTER: Farlow MR

PROVIDER: S-EPMC6398557 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

Farlow Martin R MR Thompson Richard E RE Wei Lee-Jen LJ Tuchman Alan J AJ Grenier Elaine E Crockford David D Wilke Susanne S Benison Jeffrey J Alkon Daniel L DL

Journal of Alzheimer's disease : JAD 20190101 2

<h4>Background</h4>Bryostatin-activated PKC epsilon pre-clinically induces synaptogenesis, anti-apoptosis, anti-amyloid-β oligomers, and anti-hyperphosphorylated tau.<h4>Objectives</h4>To investigate bryostatin safety, tolerability, and efficacy to improve cognition in advanced Alzheimer's disease (AD) patients.<h4>Methods</h4>A double-blind, randomized, placebo-controlled Phase II, 12-week trial of i.v. bryostatin for 150 advanced AD patients (55-85) with MMSE-2 of 4-15, randomized 1:1:1 into 2 ...[more]

PMID: 30530975

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Dataset Information

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

Background

Objectives

Methods

Results

Conclusion

Publications

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

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