Clinical Trial Finder

Inclusion Criteria:

• - Signed informed consent form.

• - Participant or parent/legal guardian is able and willing to complete seizure diaries for the duration of the study.

• - Genetic confirmation of inherited mitochondrial disease with associated epilepsy phenotype (Alpers/polymerase subunit gamma [POLG], Leigh syndrome, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS], or other genetically confirmed mitochondrial disease secondary to mitochondrial mutation).

• - Despite ongoing treatment with at least 2 antiepileptic drugs: - have ≥6 observed motor seizures occurring during the 28 days prior to the baseline visit (Day 0).

• - have ≥2 observed motor seizures in the first 14 days and ≥2 in the second 14 days of the Run-in period (Day -14).

• - do not have a consecutive 20-day seizure free period.

• - have at least 80% of seizure diary data.

• - Documented medical history of epilepsy associated with mitochondrial disease for at least 6 months prior to screening.

• - Consent to abstain from non-approved therapies for 30 days prior to the baseline visit (Day 0) and for the duration of the study.

• - Stable dose regimen of antiepileptic therapies 60 days prior to the baseline visit (Day 0).

• - Stable regimen of dietary supplements 30 days prior and, if on a ketogenic diet, stable ketogenic diet 90 days prior to the baseline visit (Day 0) and for duration of the study.

• - Electroencephalogram (EEG) at screening or historical EEG for diagnostic confirmation of seizures.

Exclusion Criteria:

• - Allergy to vatiquinone or sesame oil.

• - Aspartate transaminase (AST) or alanine transaminase (ALT) ≥2 × upper level of normal (ULN) at time of screening.

• - International normalized ratio (INR) ≥1.5 × ULN at time of screening.

• - Serum creatinine ≥1.5 × ULN at time of screening.

• - Participation in another interventional clinical trial 60 days prior to randomization or for the duration of this clinical trial.

• - Previously received vatiquinone.

• - Concomitant treatment with drug(s) that have not received regulatory agency approval for the treatment of mitochondrial diseases.

• - Concomitant treatment with idebenone.

• - Ongoing treatment with cytochrome P450 (CYP) inhibitors such as itraconazole or CYP inducers such as rifampin.

Treatment with these agents must be completed at least 4 weeks prior to enrollment.During the study, participants should not use grapefruit juice or St John's wort extract.

• - Pregnant or lactating participants or those sexually active participants who are unwilling to comply with proper birth control methods.

Females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit (Day 0).

Arms

Experimental: Vatiquinone

15 milligrams/kilogram (mg/kg) if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, 3 times per day (TID) or up to 72 weeks

Placebo Comparator: Placebo

Vatiquinone-matching placebo, administered orally, TID for up to 24 weeks followed by vatiquinone 15 mg/kg if body weight <13 kg, and 200 mg if body weight ≥13 kg, administered orally, TID for up to 48 weeks.

Interventions

Drug: - Vatiquinone

Vatiquinone will be administered per the treatment arm description.

Other: - Placebo

Vatiquinone-matching placebo will be administered per the treatment arm description