An Open-Label Phase 2a Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Dementia with Lewy Bodies (DLB)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eip Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Aug 2024 → 25 Mar 2026

Decision date (initial)

2024-06-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

EIP Pharma

External identifiers

EU CT number

2024-511446-39-00

ISRCTN

ISRCTN06815965

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

Evaluate the safety and tolerability and pharmacokinetics (PK) of 80mg neflamapimod given twice or three times daily in patients with dementia with Lewy bodies

Conditions and MedDRA coding

Dementia with Lewy Bodies (DLB)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Men and women aged ≥55 years.
2. Participant is willing and able to provide written informed consent.
3. Probable DLB by consensus criteria (McKeith et al, 2017; McKeith et al, 2020).
4. MoCA score ≥18 OR CDR global score (CDR-GS) ≤ 1.0 during Screening.
5. If the patient is currently receiving cholinesterase inhibitor and/or memantine 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 enrollment (Day 1/first dose). Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study. If the patient is not currently receiving such therapy, but received such therapy previously, that therapy must have been discontinued at least 3 months prior to enrollment.
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. Must have reliable informant or caregiver.

Exclusion criteria 11

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), Frontotemporal dementia (FTD), or Parkinson’s disease (PD).
2. 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.
3. Diagnosis of alcohol or drug abuse within the previous 2 years.
4. 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.
5. 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.
6. Known tuberculosis, human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
7. Participated in a study of an investigational drug less than 6 weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
8. Receipt of a live vaccine, with the exception of influenza, within 4 weeks before starting study drug treatment.
9. History of previous neurosurgery to the brain within the past five years.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To evaluate safety and tolerability of 80 mg neflamapimod given twice or three times daily over 24 weeks of dosing
2. To evaluate multiple dose PK parameters of 80mg BID and 80mg TID

Secondary endpoints 10

1. Changes in the mean composite score for Alzheimer’s Disease Neuroimaging Initiative Executive Functioning composite scale (ADNI-EF) (Gibbons, et al., 2012) from baseline to 24 weeks
2. Change in the Clinical Dementia Rating Sum of Boxes (CDR-SB) score from baseline to 24 weeks
3. Change in Timed Up and Go (TUG) test results from baseline to 24 weeks
4. Changes in the Mild Behavioral Impairment Checklist (MBI-C) scale
5. Changes in the Montreal Cognitive Assessment (MOCA)
6. Changes in the Alzheimer’s Disease Cooperative Study –Activities of Daily Living Inventory for Mild Cognitive Impairment (ADCS- ADL-MCI)
7. Changes in the Go no Go task
8. Change in Dementia Cognitive Fluctuations Scale (DCFS).
9. Change in hallucinations as measured by the Parkinson’s disease-associated psychotic symptoms questionnaire (PDAP)
10. Change in volume of nucleus basalis of Meynert (NBM) as assessed by structural Magnetic Resonance Imaging (MRI)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eip Pharma Inc.

Sponsor organisation

Eip Pharma Inc.

Address

120 Saint James Avenue

City

Boston

Postcode

02116-5001

Country

United States

Scientific contact point

Organisation

Eip Pharma Inc.

Contact name

John Alam

Public contact point

Organisation

Eip Pharma Inc.

Contact name

EIP Pharma General mailbox

Third parties 4

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications