Clinical trial NCT05046106: MLC1501 Study Assessing Efficacy in STROke Recovery
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Efficacy and Safety Study of MLC1501 in Patients With Stroke
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Stroke
Stroke, Ischemic
Strokes Thrombotic
Stroke Sequelae
Stroke, Cardiovascular
Stroke, Embolic
Stroke, Cryptogenic
Keywords: stroke
MLC1501
MAEStro
stroke recovery
neurorestoration
Lead sponsor: Moleac Pte Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-16
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blind, placebo-controlled, dose-response study of MLC1501 in patients with stroke. Eligible participants will be randomized in a 1:1:1 ratio to orally receive MLC1501 low-dose twice a day, MLC1501 high-dose twice a day, or matching placebo for 24 weeks.

Detailed description: A total of 540 patients will be included with approximately 180 participants randomized to each treatment arm. Randomization will be performed centrally and stratified according to the following factors at the time of randomization: NIHSS (8 to 12, 13 to 18), age (\<65 years, ≥65 years) and received either intravenous or endovascular thrombolysis/thrombectomy (no, yes).

Efficacy clinical assessments will include mRS, FMA, ARAT, 10MWT, NIHSS, Barthel Index, EQ-5D-5L, MoCA, PROMIS-10, and occurrence of recurrent vascular event.

Each participant will undergo standard safety assessments including physical exam and laboratory parameters, and be observed for adverse events for the duration of the study. Electrocardiogram (ECG), hematology, clinical chemistry, coagulation, and urinalysis will be performed at specified intervals. The C-SSRS will be used to screen for suicidal ideation and behavior. Blood samples will be collected and stored for future studies on circulating compounds and pharmacokinetics.

Eligibility criteria: Inclusion Criteria:

* Male or female.
* 18 years old or older.
* Diagnosed with acute ischemic stroke with compatible brain imaging findings between 2 days to 7 days prior to inclusion. Patients who undergo intravenous or endovascular thrombolysis or thrombectomy must be considered stable for at least 24 hours post-procedure prior to inclusion.
* NIHSS total score of 8 to 18 (inclusive) at the time of inclusion with a combined score of at least 2 on the NIHSS motor items 5A or 5B and/or 6A or 6B.
* A candidate for active rehabilitation in the opinion of the treating physician.
* Able to comply with the requirements of the protocol and provide written informed consent by patient or legal representative before any study-specific procedure is performed.

Exclusion Criteria:

* Pre-stroke modified Rankin score of \>1.
* Contraindication to any of the study procedures.
* Participation in another investigational drug or device trial within the past 30 days.
* Intake of warfarin in the past one week or expected to be on warfarin while in the study.
* Women who are pregnant, breastfeeding, of child-bearing potential or planning to become pregnant during the study. Menopausal/post-menopausal women without menstruation for 12 consecutive months or surgically sterilized women may be included. Intake of oral contraceptive pills or hormone replacement therapy is not allowed. Use of mechanical barriers, e.g., condom, intrauterine device, are allowed. Local contraception requirements for clinical trials should be followed.
* Any known food allergy or hypersensitivity to Astragalus membranaceus, Ligusticum chuanxiong, Polygala tenuifolia, Angelica sinensis, or members of the Fabaceae/Leguminosae family (e.g., legume, pea, bean), Polygalaceae family (e.g., milkwort, snakeroot), Apiaceae/Umbelliferae family (e.g., anise, caraway, carrot, celery, dill, parsley, parsnip), or Quillaja bark (soapbark).
* Evidence of other significant non-ischemic brain lesion which could affect long-term function or disability.
* Evidence of advanced medical condition that would affect study assessment and follow-up, such as cancer, renal failure, liver cirrhosis, severe dementia, or psychosis.
* Any other medical or psychiatric or cognitive condition which, in the study investigator's opinion, may jeopardize the patient by his/her participation in this study, may hamper his/her ability to complete procedures required in the study, affect study assessment and follow-up, or affect the validity of the study results

Primary outcomes:
measure: modified Rankin Scale
timeFrame: 24 weeks
Secondary outcomes:
measure: Fugl-Meyer motor Assessment (FMA)
timeFrame: 12, 24 weeks
measure: Action Research Arm Test (ARAT)
timeFrame: 12, 24 weeks
measure: Timed 10-Meter Walk Test (10MWT)
timeFrame: 12, 24 weeks
measure: National Institute of Health Stroke Scale total and motor scores
timeFrame: 12, 24 weeks
measure: Barthel Index
timeFrame: 4, 12, 24, 36 weeks
measure: EuroQol 5 Dimensions 5 Levels
timeFrame: 4, 12, 24, 36 weeks
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 12, 24 weeks
measure: Occurrence of recurrent vascular event
timeFrame: 24, 36 weeks
measure: Patient Reported Outcome Measurement Information System - Global Health
timeFrame: 12, 24 weeks
measure: Columbia-Suicide Severity Rating Scale screen
timeFrame: 4, 12, 24, 36 weeks
measure: Adverse events
timeFrame: up to 36 weeks
measure: modified Rankin Scale
timeFrame: 4, 12 and 36 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Departments of Pharmacology and Psychological Medicine, National University of Singapore
name: Christopher Chen, BMBCh, MRCP, FAMS, FRCPE
role: PRINCIPAL_INVESTIGATOR
References: