Proof-of-Concept Study of a Selective p38 MAPK Alpha Inhibitor, Neflamapimod, in Subjects With Mild Alzheimer's Disease
Summary
This is a phase 2b, double-blind, placebo controlled proof-of-concept study of a an oral small molecule selective inhibitor of p38 alpha kinase, neflamapimod, administered for 24 weeks in subjects with mild Alzheimer's disease. The primary objective is to demonstrate significant improvement relative to placebo-treatment in episodic memory function, as assessed by the Hopkins Verbal Learning Test. Secondary endpoints include Clinical Dementia Rating scale (CDR), Wechsler Memory Scale (WMS), Mini-Mental-Status-Examination (MMSE) and Cerebrospinal fluid (CSF) biomarkers of AD disease activity and progression.
Timeline
- Start
- 2017-12-29
- Primary completion
- 2019-06-30
- Completion
- 2019-07-31
Outcome
Missed primary endpoint
registry analysis (other test); Placebo Arm vs Neflamapimod Arm; p = 0.564; Mean Difference (Final Values) -0.06098 (95% CI -0.26973 to 0.14777); Mixed Models Analysis NCT03402659 ↗
paper No significant differences between treatment groups were observed in the primary or secondary clinical endpoints. PMID 34044875 ↗
release “the 24-week, double-blind placebo-controlled Phase 2b study evaluating the oral p38⍺ kinase inhibitor neflamapimod in early-stage Alzheimer’s disease did not meet its primary objective” cervomed.com ↗
Publications
- Prins ND, Harrison JE, Chu HM, Blackburn K, Alam JJ, Scheltens P; REVERSE-SD Study Investigators. A phase 2 double-blind placebo-controlled 24-week treatment clinical study of the p38 alpha kinase inhibitor neflamapimod in mild Alzheimer's disease. Alzheimers Res Ther. 2021 May 27;13(1):106. doi: 10.1186/s13195-021-00843-2.
- Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Neflamapimod | Small molecule | 40 mg | Oral |