Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease Subjects With Refractory Epilepsy

PTC743-MIT-001-EP

This is a parallel-arm, double-blind, placebo-controlled study with a screening phase that includes a 28-day run-in phase to establish baseline seizure frequency, followed by a 24-week, randomized, placebo-controlled phase. After completion of the randomized, placebo-controlled phase, participants may enter a 48-week, long-term, extension phase during which they will receive open-label treatment with vatiquinone.

2020-09-28

2023-03-18

2023-12-27

Completed

Early phase I

60

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 mutations (Pontocerebellar Hypoplasia Type 6 \[PCH6\], nuclear DNA RARS2 mutation) or myoclonic epilepsy with ragged red fibers (MERRF, mitochondrial DNA \[mtDNA\] mitochondrially encoded tRNA lysine \[MT-TK\] 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 except for participants who are \<2 years of age at the time of screening (participants \<2 years of age can be considered for enrollment if all other screening criteria are met due to the potential for rapid progression in these participants). * Consent to abstain from non-approved therapies for 30 days prior to the screening visit and for the duration of the study. * Stable dose regimen of antiepileptic therapies 30 days prior to the screening visit. * Stable regimen of dietary supplements 30 days prior and, if on a ketogenic diet, stable ketogenic diet 90 days prior to the screening visit and for duration of the study. * Electroencephalogram (EEG) at screening or historical EEG up to 6 months prior to screening for diagnostic confirmation of seizures. Exclusion Criteria: * Allergy to vatiquinone or sesame oil. * Aspartate transaminase (AST) or alanine transaminase (ALT) ≥3 × upper level of normal (ULN) at time of screening. * International normalized ratio (INR) \>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 and use of artisanal (non-Epidiolex cannabidiol) cannabidiol therapies. * Concomitant treatment with idebenone. * Ongoing treatment with strong cytochrome P450 (CYP) inhibitors such as itraconazole or strong 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/grapefruit juice or St John's wort extract. * Pregnant or lactating participants or those male or female sexually active participants who are unwilling to comply with proper birth control methods from the time consent is signed until 30 days after treatment discontinuation. Females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit (Day 0). * Comorbidities that may confound study results (for example, fat malabsorption syndrome, other mitochondrial disorders) in the opinion of the investigator.

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2024-03-08