Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

Study Overview
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Brief Summary
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This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults diagnosed with MELAS.

Detailed Description
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IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days

Official Title
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A Phase 2a Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

Conditions
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MELAS

Intervention / Treatment
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* Drug: IW-6463 Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior genetic confirmation of a known mitochondrial disease mutation Neurological features of MELAS (can be based on medical history) Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L) Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 90 days after the final dose of study drug. Male participants must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception and agree to refrain from sperm donation from the Screening Visit through 90 days after the final dose of study drug. Other inclusion criteria per protocol Exclusion Criteria: Positive pregnancy test at Screening or on Day 1 Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg at Screening or predose at Day 1 Hypertension defined as systolic BP >160 mmHg or diastolic BP >100 mmHg, at Screening or predose at Day 1 Uncontrolled diabetes Severe gastrointestinal dysmotility as determined by the investigator that may impact compliance and/or oral drug administration, absorption and exposure. Unable to fast for 3-4 hours after a meal Unable or unwilling to adhere to the study schedule, lifestyle restrictions, assessment requirements or, in the clinical judgment of the investigator, is otherwise not suitable for study participation. Current or past history of clinically significant cardiomyopathy and/or cardiac conduction abnormality Used any nicotine-containing products (eg, cigarettes, e-cigarettes, vape pens, cigars) within 1 month of enrollment Other exclusion criteria per protocol

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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single-arm study with daily dosing for up to 29 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IW-6463<br>Open-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg. | Drug: IW-6463 Tablets<br>* IW-6463 tablets administered orally (daily)<br>* Other names: CY6463;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Study Drug Dose Reductions or Discontinuations Due to ≥ 1 Treatment Emergent Adverse Event (TEAE) | A TEAE is defined as an adverse event (AE) with an onset that occurs between the first dose of study drug and the end of study period. AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment. | From first dose date to Day 43 (±4) | 
| Number of Participants Who Experienced ≥1 AE, TEAE, Serious AE (SAE), or TEAE of Special Interest (AESI) | AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment. A TEAE is defined as an AE with an onset that occurs from the first dose of study drug up until the end of study period. An SAE is an AE that fulfills 1 or more of the following: results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent 1 of the outcomes listed above. Events were categorized as mild, moderate, or severe and as related or unrelated to study drug. AESIs include bleeding events, symptomatic hypotensive events and/or tachycardia, dizziness, syncope, and TEAEs related to change of neurobehaviors (ie, suicidality or euphoria). | From first dose date to Day 43 (±4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mitochondrial disease