A Phase 2b 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

9 Aug 2023 → 16 Jun 2025

Decision date (initial)

2023-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

NIA Grant

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to demonstrate the efficacy of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB).

Secondary objectives 3

1. Demonstrate that neflamapimod improves motor function in patients with DLB, compared to placebo, as assessed by the Timed Up and Go Test (TUG).
2. Demonstrate that neflamapimod improves cognition, compared to placebo, as assessed by a DLB-specific Neuropsychological Test Battery (NTB) in patients with DLB. The NTB is comprised of: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test.
3. 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 by the Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC).

Conditions and MedDRA coding

Subjects aged ≥55 years with probable Dementia with Lewy Bodies DLB by consensus criteria (McKeith et al, 2017), including a positive DaTscan™ and a CDR Global Score of 0.5 or 1.0. If the DaTscan is negative, but the subject has historical polysomnography (PSG)-verified REM sleep behavioral disorder (RBD), this will also qualify as probable DLB.

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Men and women aged ≥55 years.
2. Subject is willing and able to provide written informed consent.
3. Probable DLB by consensus criteria, including a positive DaTscan™. If the DaTscan is negative, but the subject has historical polysomnography (PSG)-verified REM sleep behavioral disorder (RBD), this will also qualify as probable DLB.
4. CDR Global Score less than 2.0 at Screening.
5. 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. If the patient is not currently receiving cholinesterase inhibitor therapy, that therapy must have been discontinued at least 3 months prior to randomization.
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 12

1. Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB).
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 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 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.
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. Unwilling or unable to adhere to contraception requirements specified in the protocol.
12. If female 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 1

1. Change (from Baseline to Week 16) in CDR-SB in neflamapimod treated-subjects compared to the placebo-treated subjects.

Secondary endpoints 3

1. Change (from Baseline to Week 16) in TUG in neflamapimod-treated subjects compared to placebo-recipients.
2. Change (from Baseline to Week 16) in the composite score of the NTB, including tests of attention, executive function, and visual learning in neflamapimod-treated subjects compared to placebo-recipients.
3. ADCS-CGIC score at Week 16 in neflamapimod-treated subjects compared to placebo-recipients.

Investigational products

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

Test 1

Placebo 1

Auxiliary 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

Jennifer Conway

Public contact point

Organisation

Eip Pharma Inc.

Contact name

EIP Pharma general mailbox

Third parties 11

Locations

1 EU/EEA country · 3 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 10 files

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

Application history

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