Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies

NCT ID: NCT04001517

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2020-06-30

Brief Summary

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1) administered with food for 16 weeks in subjects with DLB. The primary objective is to evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific Cogstate Neuropsychological Test Battery (NTB). Secondary endpoints include the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI-10), Timed Up and Go Test, and electroencephalogram (EEG) as a potential biomarker for DLB.

Conditions

Dementia With Lewy Bodies (DLB)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Neflamapimod

40 mg capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing \<80 kg or the TID regimen if weighing ≥80 kg

Group Type: EXPERIMENTAL

Neflamapimod

Intervention Type: DRUG

Double-Blind, Placebo-Controlled

Placebo

40 mg matching placebo capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing \<80 kg or the TID regimen if weighing ≥80 kg

Group Type: PLACEBO_COMPARATOR

Neflamapimod

Intervention Type: DRUG

Double-Blind, Placebo-Controlled

Interventions

Neflamapimod

Double-Blind, Placebo-Controlled

Intervention Type: DRUG

Eligibility Criteria

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. Probable DLB and identified cognitive deficits, according to current consensus criteria (McKeith et al, 2017), specifically one core clinical feature and a positive DaTscan. If a negative DaTscan, but the subject has historical PSG-verified RBD, the subject would also qualify.

4. MMSE score of 15-28, inclusive, during Screening.

5. Currently receiving cholinesterase inhibitor therapy, having 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.

6. Normal or corrected eye sight 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. 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. 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.

3. 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.

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.

7. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.

8. Participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.

9. History of previous neurosurgery to the brain.

10. If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.

11. 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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Worldwide Clinical Trials

OTHER

Sponsor Role: collaborator

EIP Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Alam, MD

Role: STUDY_DIRECTOR

EIP Pharma

Locations

University of California San Diego (UCSD)

La Jolla, California, United States

Pacific Neuroscience Institute

Santa Monica, California, United States

University of Colorado

Aurora, Colorado, United States

Elite Clinical Research

Miami, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Charlestown, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Cleveland Clinic - Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Summit Research Network

Portland, Oregon, United States

Oregon Health & Science University

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Virginia

Charlottesville, Virginia, United States

National Clinical Research, Inc.

Richmond, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

University of Washington

Seattle, Washington, United States

Inland Northwest Research

Spokane, Washington, United States

Brain Research Center

's-Hertogenbosch, , Netherlands

Brain Research Center

Amsterdam, , Netherlands

Countries

United States; Netherlands

References

Alam JJ, Maruff P, Doctrow SR, Chu HM, Conway J, Gomperts SN, Teunissen C. Association of Plasma Phosphorylated Tau With the Response to Neflamapimod Treatment in Patients With Dementia With Lewy Bodies. Neurology. 2023 Oct 24;101(17):e1708-e1717. doi: 10.1212/WNL.0000000000207755. Epub 2023 Sep 1.

Reference Type: DERIVED

PMID: 37657939 (View on PubMed)

Jiang Y, Alam JJ, Gomperts SN, Maruff P, Lemstra AW, Germann UA, Stavrides PH, Darji S, Malampati S, Peddy J, Bleiwas C, Pawlik M, Pensalfini A, Yang DS, Subbanna S, Basavarajappa BS, Smiley JF, Gardner A, Blackburn K, Chu HM, Prins ND, Teunissen CE, Harrison JE, Scheltens P, Nixon RA. Preclinical and randomized clinical evaluation of the p38alpha kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration. Nat Commun. 2022 Sep 21;13(1):5308. doi: 10.1038/s41467-022-32944-3.

Reference Type: DERIVED

PMID: 36130946 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

EIP19-NFD-501

Identifier Type: -

Identifier Source: org_study_id