A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy (MIT-E)
Clinicaltrials.gov ID# 04378075
Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of vatiquinone in reducing the frequency of observable motor seizures in patients with genetically defined mitochondrial disease and associated refractory epilepsy.
Eligibility:
Inclusion Criteria:
To be eligible for enrollment in the study, subjects must meet all of the following inclusion criteria:
1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his/her parent/legal guardian) has been informed of all pertinent aspects of the trial
2. Age <18 years at time of randomization
3. Subject or parent/legal guardian is able and willing to complete seizure diaries for the duration of the study
4. Genetic confirmation of inherited mitochondrial disease with associated epilepsy phenotype (Alpers/POLG, Leigh syndrome, MELAS) -OR-
5. other genetically confirmed mitochondrial diseases secondary to mitochondrial mutations (Pontocerebellar Hypoplasia Type 6 [PCH6], nuclear DNA RARS2 mutation) -OR-
6. myoclonic epilepsy with ragged red fibers (MERRF, mitochondrial DNA [mtDNA] mitochondrially encoded tRNA lysine [MT-TK] mutation)
7. Despite treatment with at least 2 AEDs:
a. Have ≥6 observed motor seizures occurring during the 28 days prior to the Baseline Visit
b. Have ≥2 observed motor seizures in the first 14 days and ≥2 in the second 14 days of the Run-in period
c. Do not have a consecutive 20-day seizure free period -and-
d. Have at least 80% of seizure diary data
e. No changes to the AED regimen will be allowed (except weight-based dose adjustments) during the first 24-week period.
8. Documented medical history of epilepsy associated with mitochondrial disease for at least 6 months prior to screening
9. Consent to abstain from non-approved therapies for 30 days prior to the Screening Visit and for the duration of the study
10. Stable dose regimen of antiepileptic therapies 30 days prior to the Screening Visit
11. 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
12. Electroencephalogram (EEG) at Screening or historical EEG up to 6 months prior to screening for diagnostic confirmation of epilepsy
Exclusion Criteria:
Subjects will be excluded from enrollment if any of the following exclusion criteria apply:
1. Allergy to vatiquinone or sesame oil
2. Aspartate transaminase (AST) or alanine transaminase (ALT) ≥3×ULN at time of Screening
3. INR ≥ULN at time of screening
4. Serum creatinine ≥1.5×ULN at time of screening
5. Participation in another interventional clinical trial 60 days prior to randomization or for the duration of this clinical trial
6. Previously received vatiquinone
7. 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
8. Concomitant treatment with idebenone
9. 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, subjects should not use grapefruit/grapefruit juice or St John’s wort extract.
10. Pregnant or lactating subjects or those male or female sexually active subjects who are unwilling to comply with proper birth control methods as defined in Section 7.5.10 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
11. Comorbidities that may confound study results (eg, fat malabsorption syndrome, other mitochondrial disorders) in the opinion of the investigator
Recruitment Status:
Not yet recruiting, anticipated site activation in March
Primary Investigator:
Michele Spencer-Manzon, MD
Contact Information:
PI: michele.spencer-manzon@yale.edu
Coordinator: michele.jasne@yale.edu
(203) 785-6351 (voicemail)