MLC1501 Study Assessing Efficacy in STROke Recovery

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Efficacy and Safety Study of MLC1501 in Patients With Stroke

Conditions
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Stroke, Stroke, Ischemic, Strokes Thrombotic, Stroke Sequelae, Stroke, Cardiovascular, Stroke, Embolic, Stroke, Cryptogenic

Intervention / Treatment
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* Drug: MLC1501
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>500-mg placebo capsule, 4 capsules twice a day for 24 weeks. | Other: Placebo<br>* Caramel, chocolate brown, flavor (E_1982648), dextrin<br>|
| Active Comparator: MLC1501 Low-dose<br>MLC1501 low-dose 500-mg capsule, 4 capsules twice a day for 24 weeks. | Drug: MLC1501<br>* Powdered extract of Radix astragali, Rhizoma chuanxiong, Radix angelica sinensis, Radix polygala<br>|
| Active Comparator: MLC1501 High-dose<br>MLC1501 high-dose 500-mg capsule, 4 capsules twice a day for 24 weeks. | Drug: MLC1501<br>* Powdered extract of Radix astragali, Rhizoma chuanxiong, Radix angelica sinensis, Radix polygala<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin Scale | The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 (no symptoms at all) to 5 (severe disability). A separate category of 6 is usually added for patients who expire. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer motor Assessment (FMA) |  | 12, 24 weeks | 
| Action Research Arm Test (ARAT) |  | 12, 24 weeks | 
| Timed 10-Meter Walk Test (10MWT) |  | 12, 24 weeks | 
| National Institute of Health Stroke Scale total and motor scores | The maximum possible score is 42 (severe), with the minimum score being a 0 (no symptoms) | 12, 24 weeks | 
| Barthel Index |  | 4, 12, 24, 36 weeks | 
| EuroQol 5 Dimensions 5 Levels | EQ5D-5L has 5 response levels: level 1 (no problems), 2 (slight), 3 (moderate), 4 (severe). Sometimes it is more convenient to dichotomies the levels into 'no problem's (level 1) and 'any problems' (level 2 to 5). In total, there are 3,125 possible unique health states defined by the EQ-5D-5L, with 11111 and 55555 representing the best and worst health states | 4, 12, 24, 36 weeks | 
| Montreal Cognitive Assessment (MoCA) |  | 12, 24 weeks | 
| Occurrence of recurrent vascular event |  | 24, 36 weeks | 
| Patient Reported Outcome Measurement Information System - Global Health | The PROMIS Global-10 is a 10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. These scores are then standardized to the general population, using the T-Score. The average T-Score for the United States population is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient. | 12, 24 weeks | 
| Columbia-Suicide Severity Rating Scale screen | There are no specified clinical cutoffs for the C-SSRS due to the binary nature of the responses to items. When an item is endorsed, the clinician must pose follow-up inquiries to obtain additional information. The following can inform safety monitoring and treatment planning when patients endorse suicidal ideation, suicidal behavior, or both: Suicidal ideation (Item endorsement: Yes; C-SSRS Categories 1-5) Suicidal behavior (Item endorsement: Yes; C-SSRS Categories 6-10) Suicidal ideation & behavior (Item endorsement: Yes; C-SSRS Categories 1-10) | 4, 12, 24, 36 weeks | 
| Adverse events | Listing and calculating the number and percentage of subjects experiencing non-serious and serious adverse events for each dose cohort | up to 36 weeks | 
| modified Rankin Scale | The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 (no symptoms at all) to 5 (severe disability). A separate category of 6 is usually added for patients who expire. | 4, 12 and 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, MLC1501, MAEStro, stroke recovery, neurorestoration