A Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies

An Open-Label Phase 2a Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies (DLB)

The purpose of this clinical study is to evaluate the safety and tolerability (side effects) and pharmacokinetics (drug levels in the body) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.

Study Overview

• Status: Completed
• Conditions: Dementia With Lewy Bodies (DLB)
• Intervention / Treatment: Drug: neflamapimod

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hôpital Lariboisière - APHP; Centre de Neurologie Cognitive
  • Strasbourg, France, 67000
    • Strasbourg University Hospital (Les Hopitaux Universitaires de Strasbourg)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women aged ≥55 years.
2. Subject is willing and able to provide written informed consent.
3. Probable DLB by consensus criteria (McKeith et al, 2017; McKeith et al, 2020).
4. MoCA score ≥18 OR CDR global score (CDR-GS) ≤ 1.0 during Screening.
5. If the patient is currently receiving cholinesterase inhibitor and/or memantine therapy, the patient must have received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of enrollment. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study. If the patient is not currently receiving such therapy, but received such therapy previously, that therapy must have been discontinued at least 3 months prior to enrollment.
6. Normal or corrected eyesight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
7. No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
8. Received vaccination for SARS-CoV-19 unless medical contraindications prevent being vaccinated or has a history of natural infection.
9. Must have reliable informant or caregiver.

Exclusion Criteria:

1. Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB, including, but not limited to, post-stroke dementia, vascular dementia, Alzheimer's disease (AD), Frontotemporal dementia (FTD), or Parkinson's disease (PD).
2. Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
3. Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
4. Diagnosis of alcohol or drug abuse within the previous 2 years.
5. Poorly controlled clinically significant medical illness, such as hypertension (blood pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would interfere with assessment of drug safety.
6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5. If patient is taking blood thinners (e.g., warfarin), and has no known liver issues, INR >3.
7. Positive screen for human immunodeficiency virus, hepatitis B surface antigen (HbsAg), antibody (anti-HbS), hepatitis C virus (HCV) antibody or evidence of latent or active tuberculosis, active opportunistic or life-threatening infections.
8. Participated in a study of an investigational drug less than 6 weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
9. Receipt of a live vaccine, with the exception of influenza, within 4 weeks before starting study drug treatment.
10. History of previous neurosurgery to the brain within the past five years.
11. If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
12. If female who has not has not reached menopause >1 year previously or has not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positive pregnancy test result during Screening and/or is unwilling or unable to adhere to the contraception requirements specified in the protocol.
13. If female, currently pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neflamapimod, Open-label; 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)	Drug: neflamapimod; Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase 14 (p38α). It is administered orally in 40 mg capsules.; Other Names: VX-745

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety and tolerability 80 mg neflamapimod given twice daily in patients with dementia with Lewy bodies.	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	From enrollment until the end of treatment at 24 weeks
Evaluate the safety and tolerability of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.	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	From enrollment until the end of treatment at 24 weeks
Evaluate the maximum plasma concentration (Cmax) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.	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.	From enrollment until the end of treatment at 24 weeks
Evaluate the trough plasma concentration (Ctrough) of 80mg neflamapimod given twice daily in patients with dementia with Lewy bodies.	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.	From enrollment until the end of treatment at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ADNI-EF composite score from baseline to 24 weeks	Effects of neflamapimod treatment will be assessed via changes in the mean composite score for Alzheimer's Disease Neuroimaging Initiative Executive Functioning composite scale (ADNI-EF) from baseline to 24 weeks where composite scores range from -3.0 to 3.0 and a positive change in composite score indicates improvement in cognition and a negative change in composite score indicates a worsening in cognition.	From enrollment until the end of treatment at 24 weeks
Change in CDR-SB score from baseline to 24 weeks	Effects of neflamapimod treatment will be assessed via changes in the Clinical Dementia Rating Sum of Boxes (CDR-SB) score from baseline to 24 weeks. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.	From enrollment until the end of treatment at 24 weeks
Change in TUG test results from baseline to 24 weeks	Effects of neflamapimod treatment will be assessed via changes in Timed Up and Go (TUG) test results from baseline to 24 weeks. TUG scores typically range from 6 to 20 seconds with a lower score indicating better mobility and a higher score indicating worse mobility.	From enrollment until the end of treatment at 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MBI-C score from baseline to 24 weeks	Effects of neflamapimod treatment will be assessed via changes in the Mild Behavioral Impairment Checklist (MBI-C) scale from baseline to 24 weeks. The scale ranges from 0 to 102, with lower scores indicating less severe symptoms and higher scores indicating more severe symptoms.	From enrollment until the end of treatment at 24 weeks
Changes in DCFS from baseline to 24 weeks	Effects of neflamapimod treatment will be assessed via changes in the Dementia Cognitive Fluctuations Scale (DCFS) score from baseline to 24 weeks. DCFS scores range from 4 to 20 where a higher score indicates more severe cognitive fluctuations and disease worsening.	From enrollment until the end of treatment at 24 weeks
Changes hallucinations (PDAP questionnaire) from baseline to 24 weeks	Effects of neflamapimod treatment will be assessed via changes in hallucinations as measured by the Parkinson's disease-associated psychotic symptoms questionnaire (PDAP) score from baseline to 24 weeks where a higher score indicates more severe symptoms. The scores range from 0 to 9 for patient responses and 0 to 9 for caregiver responses where a lower score indicates improvement and a higher score indicates worsening in condition.	From enrollment until the end of treatment at 24 weeks
Changes in NBM volume from baseline to 16 weeks	Effects of neflamapimod treatment will be assessed via changes in volume of nucleus basalis of Meynert (NBM) as measured by structural Magnetic Resonance Imaging (MRI) from baseline to 16 weeks where a reduction in volume indicates degeneration.	From enrollment until 16 weeks

Collaborators and Investigators

• Sponsor: EIP Pharma Inc
• Collaborators: CervoMed, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2024
• Primary Completion (Actual): March 11, 2026
• Study Completion (Actual): March 25, 2026

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Dementia; France; neflamapimod
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Dementia; Lewy Body Disease; VX-745
• Other Study ID Numbers: EIP22-NFD-505; 2024-511446-39-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes