A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy

• Status: Recruiting
• Trial end date: 2023-07-19
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PTC Therapeutics

Criteria

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).