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

NCT05869669 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: EIP21-NFD-504R01AG0805362023-504373-20
• Study Type: interventional
• Target: 159
• Locations: 3 countries
• Sites: 40

Brief Summary

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.

Conditions

Dementia With Lewy Bodies

Keywords

DLB

Outcome Measures

Primary Outcomes (2)

• Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)

  The primary objective is to demonstrate 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.

  16 weeks

• Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)

  The primary objective is to demonstrate the efficacy of neflamapimod, in recipients of Drug Batch A compared to Drug Batch B, 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.

  16 weeks

Secondary Outcomes (6)

• Change in Timed Up and Go Test (TUG) in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)

  16 weeks

• Change in Timed Up and Go Test (TUG) in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)

  16 weeks

• Change in the Composite Score of the Neuropsychological Test Battery (NTB), Including Tests of Attention, Executive Function, and Visual Learning in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)

  16 weeks

• Change in the Composite Score of the Neuropsychological Test Battery (NTB), Including Tests of Attention, Executive Function, and Visual Learning in Neflamapimod-treated Participants, Drug Batch A Compared to Drug Batch B (Open-label Extension)

  16 weeks

• Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) Score at Week 16 in Neflamapimod-treated Participants Compared to Placebo Recipients (Blinded Treatment Period)

  16 weeks

Other Outcomes (1)

• Exploratory Outcome - Plasma Biomarker, Glial Fibrillary Acidic Protein (GFAP), Measurement at Week 32 (Open-label Extension)

  32 weeks

Study Arms (3)

Neflamapimod

ACTIVE COMPARATOR

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

Drug: Neflamapimod

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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).

Drug: Neflamapimod

Interventions

Neflamapimod DRUG

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

Also known as: VX-745

Neflamapimod; Open-label extension

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged ≥55 years.
• Subject or subject's legally authorized representative is willing and able to provide written informed consent.
• \. 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.
• CDR Global Score 0.5 (very mild dementia) or 1.0 (mild dementia) during Screening
• 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.
• Normal or corrected eyesight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
• No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
• Received vaccination for SARS-CoV-19 unless medical contraindications prevent being vaccinated, or has a history of natural infection.
• Must have reliable informant or caregiver.

You may not qualify if:

• 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).
• Plasma ptau181 result above the threshold that indicates evidence of pathology associated with Alzheimer's disease at Screening.
• 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.
• 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.
• Diagnosis of alcohol or drug abuse within the previous 2 years.
• 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.
• 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.
• Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
• 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.
• History of previous neurosurgery to the brain within the past five years.
• If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
• 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.
• 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.

Sponsors & Collaborators

• EIP Pharma Inc: lead
• National Institute on Aging (NIA): collaborator
• Worldwide Clinical Trials: collaborator
• CervoMed, Inc.: collaborator

Study Sites (40)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

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

Tucson, Arizona, 85718, United States

Location

UCSD Health Sciences - Movement Disorders Center

La Jolla, California, 92037, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Stanford Neuroscience Health Center

Palo Alto, California, 94304, United States

Location

SC3 Research Group

Pasadena, California, 91105, United States

Location

University of Colorado - Dept of Neurology

Aurora, Colorado, 80045, United States

Location

Georgetown Univ Hospital - Dept of Neurology

Washington D.C., District of Columbia, 20007, United States

Location

JEM Research Institute

Lake Worth, Florida, 33462, United States

Location

ClinCloud

Melbourne, Florida, 32940, United States

Location

AdventHealth Neuroscience Research

Orlando, Florida, 32804, United States

Location

Panhandle Research and Medical Clinic

Pensacola, Florida, 32503, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

Location

Johns Hopkins School of Medicine - Dept of Neurology

Baltimore, Maryland, 21287, United States

Location

Mass General Hospital/Harvard Medical School - Dept of Neurology

Charlestown, Massachusetts, 02129, United States

Location

Mayo Clinic - Alzheimer's Disease Research Center

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center - Dept of Neurological Sciences

Omaha, Nebraska, 68198, United States

Location

Cleveland Clinic - Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

Columbia University - Taub Institute/Neurology Dept

New York, New York, 10032, United States

Location

University of North Carolina - Dept of Neurology

Chapel Hill, North Carolina, 27599, United States

Location

NeuroScience Research Center

Canton, Ohio, 44718, United States

Location

Cleveland Clinic - Center for Brain Health

Cleveland, Ohio, 44195, United States

Location

Ohio State University - Dept of Neurology

Columbus, Ohio, 43221, United States

Location

Center for Cognitive Health

Portland, Oregon, 97225, United States

Location

Houston Methodist Hospital - Stanley Appel Neurology Dept

Houston, Texas, 77030, United States

Location

Sana Research

Arlington, Virginia, 22205, United States

Location

Virginia Commonwealth University - Parkinson's and Movement Disorders Center

Richmond, Virginia, 23298, United States

Location

Brain Research Center - Den Bosch

's-Hertogenbosch, 5223, Netherlands

Location

Brain Research Center - Amsterdam

Amsterdam, 1081, Netherlands

Location

Brain Research Center - Zwolle

Zwolle, 8025, Netherlands

Location

Belfast Health & Social Care Trust

Belfast, BT12 6BA, United Kingdom

Location

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

Cambridge, CB215EF, United Kingdom

Location

South London and Maudsley NHS Foundation Trust

London, SE5 8AF, United Kingdom

Location

Re:Cognition Health

London, W1G9JF, United Kingdom

Location

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

London, WC1N 3BG, United Kingdom

Location

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

Newcastle upon Tyne, NE4 5PL, United Kingdom

Location

Cornwall Partnership NHS Foundation Trust (University of Exeter)

Redruth, TR15 3QE, United Kingdom

Location

Memory Assessment and Research Centre (MARC) - Moorgreen Hospital

Southampton, SO30 3JB, United Kingdom

Location

MeSH Terms

Conditions

Lewy Body Disease

Interventions

VX-745

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 2b (hypothesis-testing), multi-center, randomized, double-blind, placebo-controlled study with an open-label extension

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 22, 2023
• Study Start: May 1, 2023
• Primary Completion: May 29, 2025
• Study Completion: June 16, 2025
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (29); NL (3); GB (8)