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

NCT ID: NCT04378075

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2023-12-27

Brief 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Vatiquinone

Intervention Type: DRUG

Vatiquinone will be administered per the treatment arm description.

Placebo

Intervention Type: OTHER

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Vatiquinone

Vatiquinone will be administered per the treatment arm description.

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

PTC743; EPI-743

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.

• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PTC Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vinay Penematsa, MD

Role: STUDY_DIRECTOR

PTC Therapeutics

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

University of Texas Health Science

Houston, Texas, United States

Seattle Children's hospital

Seattle, Washington, United States

Alberta Children's Hospital, University of Calgary

Calgary, , Canada

CHU d'Angers - Service de génétique

Angers, , France

CHU de Montpellier - Hôpital Gui de Chauliac - Département de neuropédiatrie

Montpellier, , France

A.P.H.P - Hôpital Necker-Enfants Malades - Service de Neurologie pédiatrique

Paris, , France

CHU de Strasbourg - Hôpital de Hautepierre - Service de Neuropédiatrie

Strasbourg, , France

UOC Neuropsichiatria Infantile, Istituto Neurologico Carlo Besta-Fondazione IRCCS

Milan, , Italy

U.O.C. Malattie Muscolari e Neurodegenerative, Dipartimento di Scienze Neurologiche e Psichiatriche, Ospedale Pediatrico Bambino Gesù

Roma, , Italy

PTC Clinical Site

Multiple Locations, , Japan

Instytut Pomnik-Centrum Zdrowia Dziecka, Centrum Wsparacia Pediatrycznych Badań Klinicznych

Warsaw, , Poland

Hospital Sant Joan de Déu

Barcelona, , Spain

Hospital Ruber Internacional, Neurology Department, Epilepsy Program

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Karolinska University hospital, Astrid Lindgrens Children Hospital

Stockholm, , Sweden

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

United States; Canada; France; Italy; Japan; Poland; Spain; Sweden; United Kingdom

Other Identifiers

2020-002100-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PTC743-MIT-001-EP

Identifier Type: -

Identifier Source: org_study_id