A Clinical Study to Investigate the Effect of Oral Neflamapimod on Motor Recovery After Acute Ischaemic Stroke (RESTORE)

A Double-Blind, Placebo-Controlled, Proof-of-Concept Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod on Recovery After Moderate to Severe Acute Ischaemic Stroke

The purpose of this interventional study is to determine whether neflamapimod can improve residual physical disability and/or cognitive dysfunction after Moderate to Severe Acute Ischaemic Stroke.

Study Overview

• Status: Active, not recruiting
• Conditions: Ischaemic Stroke; Moderate to Severe Acute Ischaemic Stroke
• Intervention / Treatment: Drug: Neflamapimod; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Campbelltown, New South Wales, Australia
      • Campbelltown Hospital
    • Liverpool, New South Wales, Australia
      • Liverpool Hospital
  • Queensland
    • Birtinya, Queensland, Australia
      • Sunshine Coast University Hospital
    • Brisbane, Queensland, Australia
      • Royal Brisbane and Women's Hospital
    • Southport, Queensland, Australia
      • Gold Coast University Hospital
  • Victoria
    • Box Hill, Victoria, Australia
      • Box Hill Hospital
    • Heidelberg, Victoria, Australia
      • Austin Hospital
    • Melbourne, Victoria, Australia
      • Royal Melbourne Hospital
    • Melbourne, Victoria, Australia
      • Alfred Hospital
    • St Albans, Victoria, Australia
      • Western Health- Sunshine Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants must be aged 45 years or over at the time of signing the informed consent.
• Confirmed acute ischaemic stroke in the anterior circulation (middle or anterior cerebral artery) with onset of symptoms between 2 and 7 days prior to screening and evaluation.
• National Institutes of Health Stroke Scale (NIHSS) score between 5 and 20 (inclusive) and exhibiting unilateral motor deficit (i.e. motor NIHSS ≥ 2 on affected side of the body).
• Fugl-Meyer Assessment of Motor Recovery after Ischaemic Stroke (FMMS) total motor components score of 80 or below.
• No history of learning difficulties that may interfere with their ability to complete the cognitive tests.

Exclusion Criteria:

• Evidence of progressive or unstable stroke or intra-cerebral haemorrhage in the opinion of the investigator
• Participants needing carotid surgery within 3 months
• 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.
• History of alcohol or drug abuse within the previous 2 years.
• 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 in the opinion of the Investigator.

• Abnormal laboratory tests that, in the Investigator's assessment, mean that a participant is not appropriate for participation in this study, including, but not limited to:

  1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.0

     × the upper limit of normal (ULN),

  2. Total bilirubin >1.5 × ULN, and/or
  3. International Normalised Ratio (INR) >1.5 NOTE: Participants with Gilbert's syndrome can be included with total bilirubin >1.5 x ULN as long as direct bilirubin is ≤ 1.5 x ULN)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1 neflamapimod; Neflamapimod will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. 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: Cohort 1 placebo; Placebo will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. 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
Placebo Comparator: Cohort 2 placebo; Placebo will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. Subjects will receive 2 capsules twice per day (BID) with food (i.e., with the morning and evening meals).	Drug: Placebo; Placebo is a capsule that looks just like neflamapimod but without the active ingredients
Active Comparator: Cohort 2 neflamapimod; Neflamapimod will be administered with food for 12 weeks in subjects with Moderate to Severe Acute Ischaemic Stroke. Subjects will receive 2 capsules twice per day (BID) with food (i.e., with the morning 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 12 in the Timed Up and Go Test (TUG)	The TUG test is recorded in seconds. The test has no minimum or maximum value, and an increase in the time required to complete the TUG is a worse outcome.	From enrollment until the end of treatment at 12 weeks
Change from baseline to Week 12 in National Institutes of Health Stroke Scale (NIHSS) motor score	Scores for the NIHSS range from 0 to 42 where higher scores indicate greater impairment/worsening.	From enrollment until the end of treatment at 12 weeks
Change from baseline to Week 12 in Fugl-Meyer Assessment of Motor Recovery after Stroke (FMMS) motor score (upper and lower) and total score	The FMMS test has a maximum upper motor score of 66, maximum lower motor score of 34, and a maximum total score of 212, where an increase indicates improved motor function while a decrease indicates worsening impairment.	From enrollment until the end of treatment at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with Modified Rankin Scale (mRS) score of ≤ 2 at Week 12	The mRS scores range from 0 (no symptoms) to 6 (death) where higher scores indicate greater impairment/worsening.	From enrollment until the end of treatment at 12 weeks
Change from baseline to Week 12 in mean Barthel score	The Barthel Index (BI) for Activities of Daily Living scores range from 0 (total dependency) to 100 (independent) where higher scores indicate greater independence/improvement.	From enrollment until the end of treatment at 12 weeks

Collaborators and Investigators

• Sponsor: EIP Pharma Inc
• Collaborators: CervoMed, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: May 5, 2025
• First Submitted That Met QC Criteria: May 22, 2025
• First Posted (Actual): May 23, 2025

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Substandard Drugs; Pharmaceutical Preparations; VX-745
• Other Study ID Numbers: CRVO24-NFD-601

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
• product manufactured in and exported from the U.S.: Yes