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

March 25, 2024 updated by: EIP Pharma Inc

A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1081
        • Recruiting
        • Brain Research Center - Amsterdam
        • Principal Investigator:
          • Daphne Troost, MD
        • Contact:
      • Den Bosch, Netherlands, 5223
        • Recruiting
        • Brain Research Center - Den Bosch
        • Principal Investigator:
          • Paul Dautzenberg, MD, PhD
        • Contact:
      • Zwolle, Netherlands, 8025
        • Recruiting
        • Brain Research Center - Zwolle
        • Principal Investigator:
          • Lieza Exalto, MD, PhD
        • Contact:
  • United Kingdom
      • Belfast, United Kingdom, BT12 6BA
      • Cambridge, United Kingdom, CB215EF
        • Recruiting
        • Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn Hospital - Windsor Research Unit
        • Contact:
        • Principal Investigator:
          • Leo Chouliaras, MD
      • London, United Kingdom, W1G9JF
      • London, United Kingdom, SE5 8AF
        • Recruiting
        • South London and Maudsley NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dag Aarsland, MD
      • London, United Kingdom, WC1N 3BG
        • Recruiting
        • University College London (UCL) Clinical Research Facility, University College London Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Rimona Weil, MD
      • Newcastle Upon Tyne, United Kingdom, NE4 5PL
        • Recruiting
        • Campus Ageing Research Unit (CARU) - Newcastle upon Tyne, CNTW NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Andrew Byrne, MD
      • Redruth, United Kingdom, TR15 3QE
        • Recruiting
        • Cornwall Partnership NHS Foundation Trust (University of Exeter)
        • Contact:
        • Principal Investigator:
          • Clive Ballard, MD
      • Southampton, United Kingdom, SO30 3JB
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • Barrow Neurological Institute
        • Contact:
        • Principal Investigator:
          • Parunyou Julayanont, MD
      • Sun City, Arizona, United States, 85351
        • Recruiting
        • Banner Sun Health Research Institute
        • Contact:
        • Principal Investigator:
          • David Shprecher, MD
      • Tucson, Arizona, United States, 85718
        • Recruiting
        • Banner Alzheimer's Institute - Edson Family Lewy Body Dementia Center
        • Contact:
        • Principal Investigator:
          • Kathryn Bradley, MD
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • UCSD Health Sciences - Movement Disorders Center
        • Principal Investigator:
          • Irene Litvan, MD
        • Contact:
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Memorial Hospital Presbyterian
        • Principal Investigator:
          • Aaron Ritter, MD
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford Neuroscience Health Center
        • Principal Investigator:
          • Sharon Sha, MD
        • Contact:
      • Pasadena, California, United States, 91105
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado - Dept of Neurology
        • Contact:
        • Principal Investigator:
          • Samantha Holden, MD
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown Univ Hospital - Dept of Neurology
        • Principal Investigator:
          • Yasar Torres-Yaghi, MD
        • Contact:
    • Florida
      • Boca Raton, Florida, United States, 33498
        • Recruiting
        • University of Miami - Dept of Neurology Comprehensive Center for Brain Health
        • Principal Investigator:
          • Magdalena Tolea, PhD
        • Contact:
      • Lake Worth, Florida, United States, 33462
        • Recruiting
        • Jem Research Institute
        • Principal Investigator:
          • Linda Pao, MD
        • Contact:
      • Melbourne, Florida, United States, 32940
        • Recruiting
        • ClinCloud
        • Principal Investigator:
          • Rosemary Laird, MD
        • Contact:
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth Neuroscience Research
        • Principal Investigator:
          • Anwar Ahmed, MD
        • Contact:
      • Pensacola, Florida, United States, 32503
        • Recruiting
        • Panhandle Research and Medical Clinic
        • Contact:
        • Principal Investigator:
          • Joseph Cahill, MD
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Principal Investigator:
          • Jori Fleisher, MD
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Principal Investigator:
          • Rajesh Pahwa, MD
        • Contact:
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Recruiting
        • Tandem Clinical Research
        • Principal Investigator:
          • Angela Traylor, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins School of Medicine - Dept of Neurology
        • Principal Investigator:
          • Linda Rosenthal, MD
        • Contact:
    • Massachusetts
      • Charlestown, Massachusetts, United States, 02129
        • Recruiting
        • Mass General Hospital/Harvard Medical School - Dept of Neurology
        • Principal Investigator:
          • Stephen Gomperts, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Alzheimer's Disease Research Center
        • Principal Investigator:
          • Bradley Boeve, MD
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center - Dept of Neurological Sciences
        • Contact:
        • Principal Investigator:
          • Daniel Murman, MD
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Recruiting
        • Cleveland Clinic - Lou Ruvo Center for Brain Health
        • Principal Investigator:
          • Charles Bernick, MD
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University - Taub Institute/Neurology Dept
        • Principal Investigator:
          • Lawrence Honig, MD, PhD
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina - Dept of Neurology
        • Principal Investigator:
          • Andrea Bozoki, MD
        • Contact:
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • NeuroScience Research Center
        • Principal Investigator:
          • Ryan Drake, DO
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic - Center for Brain Health
        • Principal Investigator:
          • Babak Tousi, MD
        • Contact:
      • Columbus, Ohio, United States, 43221
        • Recruiting
        • Ohio State University - Dept of Neurology
        • Principal Investigator:
          • Douglas Scharre, MD
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97225
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital - Stanley Appel Neurology Dept
        • Principal Investigator:
          • Juan Toledo Atucha, MD
        • Contact:
    • Virginia
      • Arlington, Virginia, United States, 22205
        • Recruiting
        • Sana Research
        • Principal Investigator:
          • Eric Czander, MD
        • Contact:
      • Fairfax, Virginia, United States, 22031
        • Not yet recruiting
        • Re:Cognition Health - Fairfax
        • Principal Investigator:
          • Scott Turner, MD
        • Contact:
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University - Parkinson's and Movement Disorders Center
        • Principal Investigator:
          • Matthew Barrett, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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).
Drug: Neflamapimod
Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) provided in 40mg capsules
Other Names:
  • VX-745
Placebo Comparator: 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).
Drug: Placebo
Placebo is a capsule that looks just like neflamapimod but without the active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients.
Time Frame: 16 weeks

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Timed Up and Go Test (TUG) in neflamapimod-treated subjects compared to placebo recipients.
Time Frame: 16 weeks

Demonstrate that neflamapimod improves motor function in patients with DLB, compared to placebo, as assessed by the TUG test.

TUG scores typically range from 6 to 20 seconds with a higher score indicating worse mobility. A score of >15 indicates an increased risk of falls.
16 weeks
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) score at Week 16 in neflamapimod-treated subjects compared to placebo recipients.
Time Frame: 16 weeks

Demonstrate that neflamapimod improves global (cognition, function and behavior) disease status evaluated by a clinician with caregiver input, compared to placebo, in patients with DLB, as assessed ADCS-CGIC score.

ADCS-CGIC scores range from 1 to 7, where 1 = marked improvement, 2= moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, and 7 = marked worsening.
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 subjects compared to placebo recipients.
Time Frame: 16 weeks

Demonstrate that neflamapimod improves cognition, compared to placebo, as assessed by a DLB-specific NTB in patients with DLB. NTB includes Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB).

Each score on the individual tests is converted to a z-score, and then a total z-score for the composite is 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 indicates an improvement in cognition and a negative change in z-score indicates a worsening in cognition.
16 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory outcome - Dementia Cognitive Fluctuations Scale (DCFS)
Time Frame: 16 weeks

Change in DCFS score in neflamapimod-treated subjects compared to placebo recipients.

DCFS scores range from 4 to 20 where a higher score indicates more severe cognitive fluctuations and disease worsening.
16 weeks
Exploratory outcome - 12-item Neuropsychiatric Inventory (NPI-12)
Time Frame: 16 weeks

Change in neflamapimod-treated subjects compared to placebo recipients in the following:

  • Select domains of the NPI-12, including depression (dysphoria), apathy, hallucinations, and agitation/aggression.
  • Change in hallucinations frequency x severity score within the NPI-12 in subjects who report hallucinations at baseline.
  • Change in sleep and night-time behavior change within the NPI-12.

NPI-12 scores range from 0 to 12 for each individual domain and 0 to 144 total score, where a higher score indicates worsening of neuropsychiatric symptoms.
16 weeks
Exploratory outcome - Movement Disorder Society - Unified Parkinson's Disease Rating Scale - Part III (MSD-UPDRS3) motor examination (Part III)
Time Frame: 16 weeks

Change in MDS-UPDRS3 score in neflamapimod-treated subjects compared to placebo recipients..

MDS-UPDRS 3 scores range from 0 to 108 where a higher score indicates more severe motor symptoms.
16 weeks
Exploratory outcome - EEG
Time Frame: 16 weeks

Change in beta functional connectivity and in alpha reactivity on quantitative EEG in neflamapimod-treated subjects compared to placebo recipients..

Functional connectivity will be analyzed as Amplitude Envelope Correlation (AECc), a measure of interregional communication within the brain. AECcs are computed by correlating the amplitude (energy) envelopes of oscillatory brain signals in two different brain regions. AECc ranges between 0 and 1, with higher AECc values indicating increased functional connectivity. In this study, the primary EEG evaluation will be AECc within the beta band (13-30 Hz), i.e. beta functional connectivity.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EIP Pharma Inc

Collaborators

National Institute on Aging (NIA)
Worldwide Clinical Trials
CervoMed, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2023

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

April 12, 2023

First Submitted That Met QC Criteria

May 17, 2023

First Posted (Actual)

May 22, 2023

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EIP21-NFD-504
  • R01AG080536 (U.S. NIH Grant/Contract)
  • 2023-504373-20 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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