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

Phase 2

Active, not recruiting

• Conditions: Dementia With Lewy Bodies
• Interventions: Drug: Neflamapimod; Drug: Placebo

• Registration Number: NCT05869669
• Lead Sponsor: EIP Pharma Inc

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-04-12
• Study Start: 2023-05-01
• Study First Submitted QC: 2023-05-17
• Study First Posted: 2023-05-22
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-31
• Last Update Posted: 2024-06-04
• Primary Completion: 2024-08
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neflamapimod	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).
Placebo	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).

Primary Outcome Measures

Name	Time	Method
Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients.	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.

Secondary Outcome Measures

Name	Time	Method
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.	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.
Change in Timed Up and Go Test (TUG) in neflamapimod-treated subjects compared to placebo recipients.	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.
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) score at Week 16 in neflamapimod-treated subjects compared to placebo recipients.	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.

Trial Locations

Locations (43)

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

Johns Hopkins School of Medicine - Dept of Neurology; 🇺🇸 Baltimore, Maryland, United States

Brain Research Center - Amsterdam; 🇳🇱 Amsterdam, Netherlands

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic - Lou Ruvo Center for Brain Health; 🇺🇸 Las Vegas, Nevada, United States

Banner Sun Health Research Institute; 🇺🇸 Sun City, Arizona, United States

Sana Research; 🇺🇸 Arlington, Virginia, United States

Mass General Hospital/Harvard Medical School - Dept of Neurology; 🇺🇸 Charlestown, Massachusetts, United States

Cornwall Partnership NHS Foundation Trust (University of Exeter); 🇬🇧 Redruth, United Kingdom

NeuroScience Research Center; 🇺🇸 Canton, Ohio, United States

Cleveland Clinic - Center for Brain Health; 🇺🇸 Cleveland, Ohio, United States

Brain Research Center - Den Bosch; 🇳🇱 Den Bosch, Netherlands

Columbia University - Taub Institute/Neurology Dept; 🇺🇸 New York, New York, United States

Banner Alzheimer's Institute - Edson Family Lewy Body Dementia Center; 🇺🇸 Tucson, Arizona, United States

Stanford Neuroscience Health Center; 🇺🇸 Palo Alto, California, United States

SC3 Research Group; 🇺🇸 Pasadena, California, United States

JEM Research Institute; 🇺🇸 Lake Worth, Florida, United States

Georgetown Univ Hospital - Dept of Neurology; 🇺🇸 Washington, District of Columbia, United States

University of Miami - Dept of Neurology Comprehensive Center for Brain Health; 🇺🇸 Boca Raton, Florida, United States

ClinCloud; 🇺🇸 Melbourne, Florida, United States

Panhandle Research and Medical Clinic; 🇺🇸 Pensacola, Florida, United States

Tandem Clinical Research; 🇺🇸 Marrero, Louisiana, United States

University of North Carolina - Dept of Neurology; 🇺🇸 Chapel Hill, North Carolina, United States

Ohio State University - Dept of Neurology; 🇺🇸 Columbus, Ohio, United States

Houston Methodist Hospital - Stanley Appel Neurology Dept; 🇺🇸 Houston, Texas, United States

Virginia Commonwealth University - Parkinson's and Movement Disorders Center; 🇺🇸 Richmond, Virginia, United States

Re:Cognition Health - Fairfax; 🇺🇸 Fairfax, Virginia, United States

Belfast Health & Social Care Trust; 🇬🇧 Belfast, United Kingdom

Brain Research Center - Zwolle; 🇳🇱 Zwolle, Netherlands

Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn Hospital - Windsor Research Unit; 🇬🇧 Cambridge, United Kingdom

University College London (UCL) Clinical Research Facility, University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

Campus Ageing Research Unit (CARU) - Newcastle upon Tyne, CNTW NHS Foundation Trust; 🇬🇧 Newcastle Upon Tyne, United Kingdom

South London and Maudsley NHS Foundation Trust; 🇬🇧 London, United Kingdom

Re:Cognition Health; 🇬🇧 London, United Kingdom

Memory Assessment and Research Centre (MARC) - Moorgreen Hospital; 🇬🇧 Southampton, United Kingdom

UCSD Health Sciences - Movement Disorders Center; 🇺🇸 La Jolla, California, United States

University of Colorado - Dept of Neurology; 🇺🇸 Aurora, Colorado, United States

Mayo Clinic - Alzheimer's Disease Research Center; 🇺🇸 Rochester, Minnesota, United States

University of Nebraska Medical Center - Dept of Neurological Sciences; 🇺🇸 Omaha, Nebraska, United States

AdventHealth Neuroscience Research; 🇺🇸 Orlando, Florida, United States

Center for Cognitive Health; 🇺🇸 Portland, Oregon, United States

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States