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

NCT04378075 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: PTC743-MIT-001-EP2020-002100-39
• Study Type: interventional
• Target: 68
• Locations: 9 countries
• Sites: 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

Keywords

POLG; polymerase gamma; ALPERS; MELAS; PCH6; Pontocerebellar hypoplasia type 6; MERRF; intractable epilepsy; Mitochondrial disease; Oxidative stress; Motor seizures; Non-Motor seizures; Seizure; Refractory epilepsy; Status epilepticus; Ferroptosis; Neurodegeneration

Outcome Measures

Primary Outcomes (1)

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

  The 28-day motor seizure frequency in the double-blind period was calculated as the (number of motor seizures)/ (the number of valid days where motor seizure count information is present) \* 28 within the double-blind period. The baseline of the seizure frequency used the 28 days observations immediately prior to treatment start date for this calculation.

  Baseline to Week 24

Secondary Outcomes (22)

• 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

Study Arms (2)

Vatiquinone

EXPERIMENTAL

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

Drug: Vatiquinone; Other: Placebo

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Vatiquinone DRUG

Vatiquinone will be administered per the treatment arm description.

Also known as: PTC743, EPI-743

Vatiquinone

Placebo OTHER

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

Placebo; Vatiquinone

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (27)

University of California

San Diego, California, 92123, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Children's National Medical Center - Department Of Neurology

Washington D.C., District of Columbia, 20010, United States

Location

John Hopkins Medicine

Baltimore, Maryland, 21287, United States

Location

Pediatric Genetics Clinic (Main MGH Hospital)

Boston, Massachusetts, 02114-2696, United States

Location

Boston Children Hospital

Boston, Massachusetts, 02115, United States

Location

Children's of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science

Houston, Texas, 77030, United States

Location

Seattle Children's hospital

Seattle, Washington, 98105, United States

Location

Alberta Children's Hospital, University of Calgary

Calgary, T3B 6A8, Canada

Location

CHU d'Angers - Service de génétique

Angers, 49933, France

Location

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

Montpellier, 34295, France

Location

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

Paris, 75015, France

Location

CHU de Strasbourg - Hôpital de Hautepierre - Service de Neuropédiatrie

Strasbourg, 67200, France

Location

UOC Neuropsichiatria Infantile, Istituto Neurologico Carlo Besta-Fondazione IRCCS

Milan, 20133, Italy

Location

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

Roma, 00165, Italy

Location

PTC Clinical Site

Multiple Locations, Japan

Location

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

Warsaw, 04-730, Poland

Location

Hospital Sant Joan de Déu

Barcelona, 08950, Spain

Location

Hospital Ruber Internacional, Neurology Department, Epilepsy Program

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Karolinska University hospital, Astrid Lindgrens Children Hospital

Stockholm, S-171 76, Sweden

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Mitochondrial Diseases; Drug Resistant Epilepsy; Leigh Disease; Mitochondrial encephalopathy; MELAS Syndrome; Pontocerebellar Hypoplasia Type 6; Diffuse Cerebral Sclerosis of Schilder; MERRF Syndrome; Seizures; Status Epilepticus; Nerve Degeneration

Interventions

alpha-tocotrienol quinone

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Neuromuscular Diseases; Vascular Diseases; Cardiovascular Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Leukoencephalopathies; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Myoclonic Epilepsies, Progressive; Epilepsies, Myoclonic; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Limitations and Caveats

The study was terminated early due to Sponsor decision.

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Vinay Penematsa, MD

  PTC Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 7, 2020
• Study Start: September 28, 2020
• Primary Completion: March 18, 2023
• Study Completion: December 27, 2023
• Last Updated: March 31, 2026
• Results First Posted: March 25, 2026

Record last verified: 2025-03

Locations

CA (1); IT (2); GB (2); ES (3); FR (4); SE (1); JP (1); US (12); PL (1)