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

Mitochondrial Diseases Clinical Trial

— MIT-E  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04378075
• Other study ID #: PTC743-MIT-001-EP
• Secondary ID: 2020-002100-39
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 28, 2020
• Est. completion date: December 27, 2023

Study information

• Verified date: March 2024
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 27, 2023
• Est. primary completion date: March 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 20 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Vatiquinone
Vatiquinone will be administered per the treatment arm description.

Other:
• Placebo
Vatiquinone-matching placebo will be administered per the treatment arm description

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital, University of Calgary	Calgary
France	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
Italy	UOC Neuropsichiatria Infantile, Istituto Neurologico Carlo Besta-Fondazione IRCCS	Milano
Italy	U.O.C. Malattie Muscolari e Neurodegenerative, Dipartimento di Scienze Neurologiche e Psichiatriche, Ospedale Pediatrico Bambino Gesù	Roma
Japan	PTC Clinical Site	Multiple Locations
Poland	Instytut Pomnik-Centrum Zdrowia Dziecka, Centrum Wsparacia Pediatrycznych Badan Klinicznych	Warszawa
Spain	Hospital Sant Joan de Déu	Barcelona
Spain	Hospital Ruber Internacional, Neurology Department, Epilepsy Program	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Sweden	Karolinska University hospital, Astrid Lindgrens Children Hospital	Stockholm
United Kingdom	Great Ormond Street Hospital for Children NHS Foundation Trust	London
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne
United States	Akron Children's Hospital	Akron	Ohio
United States	John Hopkins Medicine	Baltimore	Maryland
United States	Boston Children Hospital	Boston	Massachusetts
United States	Pediatric Genetics Clinic (Main MGH Hospital)	Boston	Massachusetts
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas Health Science	Houston	Texas
United States	Children's of Minnesota	Minneapolis	Minnesota
United States	Yale School of Medicine	New Haven	Connecticut
United States	University of California	San Diego	California
United States	Seattle Children's hospital	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Children's National Medical Center - Department Of Neurology	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures per 28 Days		Day 0, Week 24
Secondary	Number of Disease-Related Hospital Days		Week 24 and up to Week 72
Secondary	Number of Participants with Occurrences or Recurrence of Status Epilepticus		Week 24 and up to Week 72
Secondary	Number of Participants with Disease-Related In-Patient Hospitalizations or Emergency Room Visits		Week 24 and up to Week 72
Secondary	Number of Disease-Related In-Patient Hospital Admissions or Emergency Room Visits		Week 24 and up to Week 72
Secondary	Percent Change From Baseline to Week 72 in Total Seizure Frequency per 28 Days		Day 0, Week 24, Week 72
Secondary	Percentage of Participants with =25%, =50%, =75%, and 100% Reduction in Motor Seizures		Week 24 and up to Week 72
Secondary	Percentage of Participants with =25%, =50%, =75%, and 100% Reduction in Total Seizures		Week 24 and up to Week 72
Secondary	Number of Participants Who Require Rescue Seizure Medication		Week 24 and up to Week 72
Secondary	Health-Related Quality of Life as Measured by the Care-Related Quality of Life of Informal Caregivers (CarerQoL-7D) Questionnaire		Week 24 and up to Week 72
Secondary	Number of Participants with Seizure Clusters		Week 24 and up to Week 72