Selected Clinical Trials

CervoMed is developing neflamapimod, an investigational, orally administered, small molecule brain penetrant that inhibits p38 alpha in the neurons of people with neurodegenerative diseases, including dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and stroke recovery.

Dementia with Lewy bodies, Phase 2b (RewinD-LB)

Study Ongoing

The Initial phase of RewinD-LB is a randomized, 16-week, double-blind, placebo-controlled clinical study evaluating oral neflamapimod (40mg TID) in 159 patients with DLB. Patients with AD co-pathology, as assessed by plasma ptau181 levels, were excluded from the study. Compared to patients with “pure” DLB – who may comprise up to 50% of the total diagnosed DLB patient population at any given time – DLB patients with AD co-pathology have significant, irreversible neuronal loss in the hippocampus. The primary endpoint in the study is change in the Clinical Dementia Rating Sum of Boxes (CDR-SB), and secondary endpoints include Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (CGIC), the Timed Up and Go test, and a cognitive test battery. The RewinD-LB study is funded by a $21.3 million grant from the National Institutes of Health’s National Institute on Aging, which is expected to be disbursed over the course of the study as costs are incurred. The study includes 43 sites across in the United States, the United Kingdom, and the Netherlands). Participants completing the 16-week Initial phase of the study were able to continue in the study while receiving neflamapimod treatment for an additional 32-week Extension phase, which includes a pre-specified data readout after the first 16 weeks.

In March 2025, CervoMed announced 16-week results from the Extension phase of its RewinD-LB Phase 2b clinical trial evaluating neflamapimod in patients with DLB without evidence of AD co-pathology in which a new batch of neflamapimod capsules (relative to the batch used in in the Initial phase of the study) led to increased plasma drug concentrations and demonstrated improvement (p<0.001 vs. old capsules; p=0.003 vs. placebo) on the primary outcome measure, change from baseline in CDR-SB, and a key secondary outcome measure, CGIC (p=0.035 against either old capsules or placebo). In addition, compared to either old capsules or placebo, a lower incidence of falls was seen in participants receiving neflamapimod from the new batch of capsules during the Extension phase.

For more information about the study please visit clinicaltrials.gov (NCT05869669). You can also view details published by the Lewy Body Dementia Association (LBDA) here.

Contact us for information about the study

Dementia With Lewy bodies Trial, Phase 2a (Strasbourg, France)

Study Ongoing

In August 2024, we initiated a Phase 2a trial in Strasbourg, France, to evaluate a twice daily regimen (80mg BID) of neflamapimod in up to 25 patients with dementia DLB with mild cognitive impairment (MoCA score >= 18 during screening). The primary objective of the trial is to obtain additional pharmacokinetic data on a dosing regimen not previously evaluated in any of our clinical trials (80mg BID) that may provide additional dosing flexibility in future trials. On an exploratory basis, we will also collect data on basal forebrain atrophy, as measured by MRI, and a broad range of clinical endpoints. Initial safety, biomarker and pharmacokinetic data from the trial is expected to be available in the fourth quarter of 2025

Dementia With Lewy bodies, Phase 2a (AscenD-LB)

Study Completed

CervoMed conducted a randomized double-blind, placebo-controlled clinical trial to investigate the effects of neflamapimod on reversing synaptic dysfunction and improving cognition in patients with mild-to-moderate dementia with Lewy bodies (DLB). The trial, was conducted in the United States and Netherlands. Patients in this study had a diagnosis of DLB that corresponded to mild to moderate disease and received a stable dose of cholinesterase inhibitor therapy (>3 months). Results of the study were positive and neflamapimod showed significant positive effects, compared to placebo, on outcomes on the gold-standard dementia rating scale (Clinical Dementia Rating Sum of Boxes, CDR-SB) and on a measure of functional mobility (Timed Up and Go, TUG, test). In addition, at the higher of two doses evaluated in the study, neflamapimod showed significant improvement, compared to placebo, on a cognitive test battery that assessed attention and executive function, with results most pronounced in patients with DLB without evidence of AD co-pathology. The results from this trial were published in the journal Nature Communications in September 2022. Additional results were published in the American Academy of Neurology journal in October 2023.

View the Nature publication at https://www.nature.com/articles/s41467-022-32944-3.

View the Neurology publication at https://n.neurology.org/content/early/2023/09/01/WNL.0000000000207755.

Alzheimer’s Disease, Phase 2b (REVERSE-SD)

Study Completed

REVERSE-SD was a double-blind, 6-month clinical trial designed to evaluate neflamapimod’s activity in reversing synaptic dysfunction, assessed by evaluating episodic memory in patients with early-stage Alzheimer’s disease. 161 patients were enrolled and randomized to either placebo or 40 mg of neflamapimod twice daily for 24 weeks. Results of the study showed target engagement of neflamapimod by demonstrating that neflamapimod reduced tau and ptau in cerebrospinal fluid (CSF) of AD patients. In this 6-month study, no discernable effect on cognition was seen on the overall population but a positive trend on cognition was observed in patients with the highest drug concentration level suggesting that a higher dose, either 40mg TID or 80mg BID, should be evaluated in subsequent longer duration trials to evaluate neflamapimod as a treatment to slow disease progression in AD.