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

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

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

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

Inclusion Criteria:

1. Prior genetic confirmation of a known mitochondrial disease mutation
2. Neurological features of MELAS (can be based on medical history)
3. Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L)
4. 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.
5. 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.
6. Other inclusion criteria per protocol

Exclusion Criteria:

1. Positive pregnancy test at Screening or on Day 1
2. Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg at Screening or predose at Day 1
3. Hypertension defined as systolic BP >160 mmHg or diastolic BP >100 mmHg, at Screening or predose at Day 1
4. Uncontrolled diabetes
5. Severe gastrointestinal dysmotility as determined by the investigator that may impact compliance and/or oral drug administration, absorption and exposure.
6. Unable to fast for 3-4 hours after a meal
7. 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.
8. Current or past history of clinically significant cardiomyopathy and/or cardiac conduction abnormality
9. Used any nicotine-containing products (eg, cigarettes, e-cigarettes, vape pens, cigars) within 1 month of enrollment
10. Other exclusion criteria per protocol