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

Plain English Summary

A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy is a Phase 3 clinical trial sponsored by PTC Therapeutics studying Mitochondrial Diseases, Drug Resistant Epilepsy, Leigh Disease, Leigh Syndrome, Mitochondrial Encephalopathy (MELAS), Pontocerebellar Hypoplasia Type 6 (PCH6), Alpers Disease, Alpers Syndrome. Tests the effectiveness and safety of Vatiquinone for treating epilepsy in mitochondrial disease patients. For patients with mitochondrial diseases and drug-resistant epilepsy, including Leigh Disease and MELAS. Participation involves a 28-day run-in phase, followed by a 24-week randomized, placebo-controlled phase, and a 48-week extension phase. Alternative treatments include other antiepileptic drugs and dietary modifications. The trial aims to enroll 68 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 2 years old, has mitochondrial disease with epilepsy, and is on at least 2 antiepileptic drugs. Not eligible if allergic to Vatiquinone, has liver or kidney issues, or is pregnant. Age: 2+ years Health: Genetic confirmation of mitochondrial disease, stable antiepileptic therapy This trial is studying Mitochondrial Diseases, Drug Resistant Epilepsy, Leigh Disease, Leigh Syndrome, Mitochondrial Encephalopathy (MELAS), Pontocerebellar Hypoplasia Type 6 (PCH6), Alpers Disease, Alpers Syndrome, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the reduction in motor seizures, which means fewer seizures for patients. The specific primary outcome measures are: Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures Per 28 Days During the Double-blind Period (Baseline to Week 24). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses the unmet need for effective treatments in mitochondrial disease patients with drug-resistant epilepsy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Mitochondrial Diseases, Drug Resistant Epilepsy, Leigh Disease, Leigh Syndrome, Mitochondrial Encephalopathy (MELAS), Pontocerebellar Hypoplasia Type 6 (PCH6), Alpers Disease, Alpers Syndrome, where improved treatment options are needed.

Investor Insight

Market size is significant, with a competitive landscape dominated by unmet needs in mitochondrial diseases. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks. Participation involves daily seizure diaries and regular check-ups. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 68 participants

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

Primary Outcomes

• Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures Per 28 Days During the Double-blind Period (Baseline to Week 24)

Secondary Outcomes

• Change From Baseline to Week 24 in Number of Disease-Related Hospitalization Days Per 28 Days in Double-Blind Period (Baseline to Week 24)
• Change From Baseline to Week 72 in Number of Disease-Related Hospitalization Days Per 28 Days in Overall Period (Baseline to Week 72)
• Change From Baseline to Week 24 in Occurrence/Recurrence of Status Epilepticus Per 28 Days in Double-blind Period (Baseline to Week 24)
• Change From Baseline to Week 72 in Occurrence/Recurrence of Status Epilepticus Per 28 Days in Overall Period (Baseline to Week 72)
• Number of Participants With Disease-Related In-Patient Hospitalizations in Double-Blind Period (Baseline to Week 24)

Full Eligibility 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 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.

Trial Locations

• University of California, San Diego, California, United States
• Stanford University, Stanford, California, United States
• Yale School of Medicine, New Haven, Connecticut, United States
• Children's National Medical Center - Department Of Neurology, Washington D.C., District of Columbia, United States
• John Hopkins Medicine, Baltimore, Maryland, United States
• Pediatric Genetics Clinic (Main MGH Hospital), Boston, Massachusetts, United States
• Boston Children Hospital, Boston, Massachusetts, United States
• Children's of Minnesota, Minneapolis, Minnesota, United States
• Akron Children's Hospital, Akron, Ohio, United States
• Baylor College of Medicine, Houston, Texas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Mitochondrial Diseases
• Drug Resistant Epilepsy
• Leigh Disease
• Leigh Syndrome
• Mitochondrial Encephalopathy (MELAS)
• Pontocerebellar Hypoplasia Type 6 (PCH6)
• Alpers Disease
• Alpers Syndrome

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