RewinD-LB - Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies

NCT ID: NCT05869669

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

159 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-01

Study Completion Date

2025-06-16

Brief Summary

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The purpose of this study is to determine whether neflamapimod can improve learning skills, problem solving skills, and memory loss in people diagnosed with DLB. More specifically, improvement in verbal learning, memory, and attention, as well as cognitive and functional performance will be measured.

Detailed Description

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Conditions

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Dementia With Lewy Bodies

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase 2b (hypothesis-testing), multi-center, randomized, double-blind, placebo-controlled study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blind

Study Groups

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Neflamapimod

Neflamapimod will be administered with food for 16 weeks in subjects with DLB. Subjects will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).

Group Type ACTIVE_COMPARATOR

Neflamapimod

Intervention Type DRUG

Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) provided in 40mg capsules

Placebo

Placebo will be administered with food for 16 weeks in subjects with DLB. Subjects will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo is a capsule that looks just like neflamapimod but without the active ingredients

Interventions

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Neflamapimod

Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) provided in 40mg capsules

Intervention Type DRUG

Placebo

Placebo is a capsule that looks just like neflamapimod but without the active ingredients

Intervention Type DRUG

Other Intervention Names

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VX-745

Eligibility Criteria

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Inclusion Criteria

1. Men and women aged ≥55 years.
2. Subject or subject's legally authorized representative is willing and able to provide written informed consent.
3. 3\. Probable DLB by consensus criteria (McKeith et al, 2017), including a positive DaTscan™. Specifically, the subject must have the presence of dementia in association with:

* At least two (2) core clinical features (fluctuating cognition, visual hallucinations, REM sleep disorder, and/or parkinsonism); or
* One (1) core clinical feature plus an abnormal DaTscan™. Historical polysomnography (PSG)-verified REM sleep behavioral disorder (RBD), FDG-PET imaging, or MIBG myocardial scintigraphy can take the place of an abnormal DaTscan™ in a patient with only one core clinical feature.
4. CDR Global Score 0.5 (very mild dementia) or 1.0 (mild dementia) during Screening
5. Background dementia therapy:

* Not currently receiving cholinesterase inhibitor therapy. If the patient received such therapy previously, that therapy must have been discontinued at least 3 months prior to randomization.
* Receiving cholinesterase inhibitor therapy alone. If the patient is currently receiving cholinesterase inhibitor 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 randomization. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study.
* Memantine therapy is allowed, if it had been started at least 3 months prior to randomization and the patient is also receiving cholinesterase inhibitor therapy. If the patient has never been on cholinesterase inhibitor therapy (naïve), then memantine monotherapy is allowed.
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), or Parkinson's disease (PD).
2. Plasma ptau181 result above the threshold that indicates evidence of pathology associated with Alzheimer's disease at Screening.
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 C-SSRS, or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
4. 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.
5. Diagnosis of alcohol or drug abuse within the previous 2 years.
6. 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.
7. 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.
8. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
9. Participated in a study of an investigational drug less than six weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
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. Weight less than 50kg.

All participants who complete the initial 16-week period of the study will be able to continue in the study and receive neflamapimod for an additional 32 weeks (8 months) regardless of whether they received neflamapimod of placebo during the the first 16 weeks.
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Worldwide Clinical Trials

OTHER

Sponsor Role collaborator

CervoMed, Inc

UNKNOWN

Sponsor Role collaborator

EIP Pharma Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Belfast Health & Social Care Trust

Belfast, , United Kingdom

Site Status

South London and Maudsley NHS Foundation Trust

London, , United Kingdom

Site Status

Re:Cognition Health

London, , United Kingdom

Site Status

Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn Hospital - Windsor Research Unit

Cambridge, , United Kingdom

Site Status

Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status

Banner Alzheimer's Institute - Edson Family Lewy Body Dementia Center

Tucson, Arizona, United States

Site Status

UCSD Health Sciences - Movement Disorders Center

La Jolla, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Stanford Neuroscience Health Center

Palo Alto, California, United States

Site Status

SC3 Research Group

Pasadena, California, United States

Site Status

University of Colorado - Dept of Neurology

Aurora, Colorado, United States

Site Status

Georgetown Univ Hospital - Dept of Neurology

Washington D.C., District of Columbia, United States

Site Status

JEM Research Institute

Lake Worth, Florida, United States

Site Status

ClinCloud

Melbourne, Florida, United States

Site Status

AdventHealth Neuroscience Research

Orlando, Florida, United States

Site Status

Panhandle Research and Medical Clinic

Pensacola, Florida, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Tandem Clinical Research

Marrero, Louisiana, United States

Site Status

Johns Hopkins School of Medicine - Dept of Neurology

Baltimore, Maryland, United States

Site Status

Mass General Hospital/Harvard Medical School - Dept of Neurology

Charlestown, Massachusetts, United States

Site Status

Mayo Clinic - Alzheimer's Disease Research Center

Rochester, Minnesota, United States

Site Status

University of Nebraska Medical Center - Dept of Neurological Sciences

Omaha, Nebraska, United States

Site Status

Cleveland Clinic - Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Site Status

Columbia University - Taub Institute/Neurology Dept

New York, New York, United States

Site Status

University of North Carolina - Dept of Neurology

Chapel Hill, North Carolina, United States

Site Status

NeuroScience Research Center

Canton, Ohio, United States

Site Status

Cleveland Clinic - Center for Brain Health

Cleveland, Ohio, United States

Site Status

Ohio State University - Dept of Neurology

Columbus, Ohio, United States

Site Status

Center for Cognitive Health

Portland, Oregon, United States

Site Status

Houston Methodist Hospital - Stanley Appel Neurology Dept

Houston, Texas, United States

Site Status

Sana Research

Arlington, Virginia, United States

Site Status

Virginia Commonwealth University - Parkinson's and Movement Disorders Center

Richmond, Virginia, United States

Site Status

Brain Research Center - Den Bosch

's-Hertogenbosch, , Netherlands

Site Status

Brain Research Center - Amsterdam

Amsterdam, , Netherlands

Site Status

Brain Research Center - Zwolle

Zwolle, , Netherlands

Site Status

University College London (UCL) Clinical Research Facility, University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Campus Ageing Research Unit (CARU) - Newcastle upon Tyne, CNTW NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Cornwall Partnership NHS Foundation Trust (University of Exeter)

Redruth, , United Kingdom

Site Status

Memory Assessment and Research Centre (MARC) - Moorgreen Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Netherlands United Kingdom

Provided Documents

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Document Type: Study Protocol: EIP21-NFD-504 Ex-US Protocol version

View Document

Document Type: Study Protocol: EIP21-NFD-504 US Protocol version

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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R01AG080536

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2023-504373-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EIP21-NFD-504

Identifier Type: -

Identifier Source: org_study_id

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