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

• Neflamapimod (Drug), also known as VX-745: Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) provided in 40mg capsules
• Placebo (Drug): Placebo is a capsule that looks just like neflamapimod but without the active ingredients

Primary outcomes

• Change from baseline to Week 12 in Fugl-Meyer Assessment of Motor Recovery after Stroke (FMMS) motor score (upper and lower) and total score [From enrollment until the end of treatment at 12 weeks]: 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.
• Change from baseline to Week 12 in the Timed Up and Go Test (TUG) [From enrollment until the end of treatment at 12 weeks]: 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.
• Change from baseline to Week 12 in National Institutes of Health Stroke Scale (NIHSS) motor score [From enrollment until the end of treatment at 12 weeks]: Scores for the NIHSS range from 0 to 42 where higher scores indicate greater impairment/worsening.

Secondary outcomes

• Proportion of participants with Modified Rankin Scale (mRS) score of ≤ 2 at Week 12 [From enrollment until the end of treatment at 12 weeks]: The mRS scores range from 0 (no symptoms) to 6 (death) where higher scores indicate greater impairment/worsening.
• Change from baseline to Week 12 in mean Barthel score [From enrollment until the end of treatment at 12 weeks]: 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.

Sex: All, ages: 45 Years to any

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)