Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Neflamapimod · 6 trials · 6 indications
The number and proportion of participants experiencing adverse events (AEs) and serious adverse events (SAEs) during the study period, categorized by severity and relationship to the study intervention.
The FMMS test has a maximum upper motor score of 66, maximum lower motor score of 34, and a maximum total score of 212, where an increase indicates improved motor function while a decrease indicates worsening impairment.
The TUG test is recorded in seconds. The test has no minimum or maximum value, and an increase in the time required to complete the TUG is a worse outcome.
Scores for the NIHSS range from 0 to 42 where higher scores indicate greater impairment/worsening.
The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of treatment-emergent Adverse events (AEs) and Serious adverse events (SAEs) during 24 weeks of treatment
The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of elevations in amino-alanine transferase (ALT) and/or aspartate amino-transferase (AST) ≥ three times the upper limit of normal during 24 weeks of treatment
The maximum plasma concentration (Cmax) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.
The trough plasma concentration (Ctrough) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.
Evaluate the efficacy of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the CDR-SB scale. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.
Change from Baseline to Week 4, Week 8, and Week 16 in the composite z-score of a study-specific Neuropsychological Test Battery (NTB) that included the following six tests: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test, and Category Fluency Test (CFT). Each score on the individual tests was converted to a z-score, and then a total z-score for the composite was calculated, in which each test is weighted equally. As the analysis is based on z-scores, there is no minimum or maximum value. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A positive change in z-score indicate an improvement in cognition, i.e., a better outcome; and a negative change in z-score indicates a worsening in cognition, i.e., a worse outcome.
Combined change from baseline in z-scores of total and delayed recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) in neflamapimod-treated subjects compared to placebo. The primary endpoint was analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. For baseline total and delayed recall, a z-score for each subject is defined by z=(x-m)/s where x is the subject's recall at baseline, and m and s are the overall mean and overall standard deviation of recall at baseline across all subjects. A composite baseline z-score for each subject is calculated using equal weighting in the following way: Z=0.5\*z-score for total recall at baseline + 0.5\*z-score for delayed recall at baseline. For HVLT-R, higher score indicates improvement.
| Arm | Type | Description |
|---|---|---|
| Neflamapimod | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Cohort 1 neflamapimod | ACTIVE_COMPARATOR | Neflamapimod will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. Subjects will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals). |
| Cohort 1 placebo | PLACEBO_COMPARATOR | Placebo will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. Subjects will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals). |
| Cohort 2 placebo | PLACEBO_COMPARATOR | Placebo will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. Subjects will receive 2 capsules twice per day (BID) with food (i.e., with the morning and evening meals). |
| Cohort 2 neflamapimod | ACTIVE_COMPARATOR | Neflamapimod will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. Subjects will receive 2 capsules twice per day (BID) with food (i.e., with the morning and evening meals). |
| Neflamapimod, Open-label | EXPERIMENTAL | Neflamapimod will be administered orally, with food, for 24 weeks in subjects with DLB. Subjects will receive 4 capsules per day (80 mg BID), two capsules in the morning and two capsules in the evening, with food (i.e., with the morning and evening meals) |
| Open-label extension | EXPERIMENTAL | Neflamapimod will be administered with food for 32 weeks in participants with DLB who have completed the blinded treatment period. Participants will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals). |
| Name | Type | Description |
|---|---|---|
| Neflamapimod | DRUG | Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) |
| Placebo | DRUG | Placebo is a capsule that looks just like neflamapimod but without the active ingredients |
Inclusion Criteria: * Men and women aged 40-85 years at Screening. * Participant or participant's legally authorized representative (where applicable) is willing and able to provide written informed consent. * Clinical diagnosis of nfvPPA by consensus criteria \[Gorno-Tempini et al, 2011\]. * At...
Neflamapimod is an investigational small molecule being studied for neurological conditions including Dementia With Lewy Bodies (DLB), Nonfluent Variant Primary Progressive Aphasia (nfvPPA), Alzheimer Disease, and Moderate to Severe Acute Ischaemic Stroke. It is in Phase 2 clinical development and has not been approved by the FDA.
Neflamapimod targets MAPK14, also known as p38 MAPK alpha, and acts as an inhibitor of this enzyme. By inhibiting MAPK14, the drug aims to modulate inflammatory and stress-response pathways implicated in neurodegenerative diseases.
Neflamapimod is being developed by CervoMed Inc., a biopharmaceutical company traded on the stock exchange under the ticker symbol CRVO. The company is conducting clinical trials to evaluate the drug's safety and efficacy in several neurological indications.
Neflamapimod is currently in Phase 2 clinical development. It has completed two Phase 2 trials in Alzheimer Disease and Dementia With Lewy Bodies, and two additional Phase 2 trials are active but not recruiting for acute ischaemic stroke and primary progressive aphasia. It is not FDA approved.
Neflamapimod has been studied in several Phase 2 trials. Completed trials include NCT03402659 in mild Alzheimer's Disease and NCT05869669 in Dementia With Lewy Bodies. Active trials include NCT06987643 for motor recovery after acute ischaemic stroke and NCT07033481 for primary progressive aphasia.
Neflamapimod is also known by the ChEMBL identifier CHEMBL119385. It is a selective inhibitor of p38 MAPK alpha, and no other alternative drug names have been reported in clinical trial registrations.