A Study to Assess TTI-0102 vs Placebo in MELAS Patients

Inclusion Criteria

• •1. Patient or Patient's legally designated representative has given written informed consent before any study-related activities are carried out and is able to understand the full nature and purpose of the trial, including possible risks and adverse effects. Patient has provided assent according to local/institutional requirements.
• •2. Males and females between 16 and 60 years of age at screening.
• •3. Diagnosis of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), defined as:
• •\- mtDNA mutation known to be associated with MELAS and MELAS phenotype (Emmanuele et al., 2022) including but not limited to: m.3243A\>G, m.13513G\>A, m.10191T\>C, m. 3271T\>C, m. 13136\_15374del, m. 8363G\>A. Mutation must have heteroplasmy \>50% characterized by mutation load in urinary epithelium or blood.
• •AND
• •\- two or more of the following clinical symptoms indicative of MELAS phenotype: diabetes, myopathy, seizures, at least one historic stroke-like episode, and exercise intolerance.
• •4. Moderate disease severity defined as Newcastle Mitochondrial Disease Adult Scale (NMDAS) score between 15 to 45 inclusive.
• •5. Able to complete a 12-minute walk test (12-MWT) distance of at least 150 meters and no more than 1000 meters within 30 days prior to, or at time of screening.
• •6. Subjects regularly taking dietary supplements including but not limited to creatine, alpha-lipoic acid, CoQ10, B vitamins, levocarnitine shall have been taking them for at least 3 months pre-study and will agree to continue taking them throughout the study (from the Screening Visit to Study Exit).
• •7. With respect to concomitant medications, the subject must:
• •1. Be willing to abstain from initiating new dietary supplements and non-prescribed medications, except as permitted by the Investigator throughout the study.
• •2. Be on a stable dose of medications prescribed for seizure management and prevention. Stable dose in this context means unchanged for at least 30 days prior to the Screening Visit.
• •8. Willing and able to comply with study drug dosing requirements, i.e., able to ingest study drug solution orally.
• •9. Female participants:
• •* Must be of nonchildbearing potential (i.e., surgically sterilized \[hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit\]) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause, and a follicle-stimulating hormone \[FSH\] level \>40 IU/L at the screening visit), or
• •* If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to the use of acceptable forms of highly effective contraception (refer to protocol Section 19.2) from the time of signing the consent form until at least 30 days after the last dose of the study drug.
• •10. Male participants:
• •* Engaging in any sexual intercourse, including those who are infertile and do not produce sperm (e.g. post-vasectomy), must abstain from unprotected sex until the Study Exit visit.
• •* Must agree to abstain from sperm donation, and if engaging in sexual intercourse with a female of child bearing potential must agree to the use of an acceptable form of highly effective contraception (refer to protocol Section 19.2) from the time of signing the consent form until at least 30 days after the last dose of study drug.
• •11. Have suitable venous access for blood sampling.
• •12. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.