A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy (MIT-E)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04378075 |
|
Recruitment Status :
Completed
First Posted : May 7, 2020
Last Update Posted : March 8, 2024
|
Sponsor:
PTC Therapeutics
Information provided by (Responsible Party):
PTC Therapeutics
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Mitochondrial Diseases Drug Resistant Epilepsy Leigh Disease Leigh Syndrome Mitochondrial Encephalopathy (MELAS) Pontocerebellar Hypoplasia Type 6 (PCH6) Alpers Disease Alpers Syndrome | Drug: Vatiquinone Other: Placebo | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease Subjects With Refractory Epilepsy |
| Actual Study Start Date : | September 28, 2020 |
| Actual Primary Completion Date : | March 18, 2023 |
| Actual Study Completion Date : | December 27, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 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
|
Drug: Vatiquinone
Vatiquinone will be administered per the treatment arm description.
Other Names:
Other: Placebo Vatiquinone-matching placebo will be administered per the treatment arm description |
|
Placebo Comparator: 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.
|
Other: Placebo
Vatiquinone-matching placebo will be administered per the treatment arm description |
Primary Outcome Measures :
- Percent Change From Baseline to Week 24 in the Number of Observable Motor Seizures per 28 Days [ Time Frame: Day 0, Week 24 ]
Secondary Outcome Measures :
- Number of Disease-Related Hospital Days [ Time Frame: Week 24 and up to Week 72 ]
- Number of Participants with Occurrences or Recurrence of Status Epilepticus [ Time Frame: Week 24 and up to Week 72 ]
- Number of Participants with Disease-Related In-Patient Hospitalizations or Emergency Room Visits [ Time Frame: Week 24 and up to Week 72 ]
- Number of Disease-Related In-Patient Hospital Admissions or Emergency Room Visits [ Time Frame: Week 24 and up to Week 72 ]
- Percent Change From Baseline to Week 72 in Total Seizure Frequency per 28 Days [ Time Frame: Day 0, Week 24, Week 72 ]
- Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Motor Seizures [ Time Frame: Week 24 and up to Week 72 ]
- Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Total Seizures [ Time Frame: Week 24 and up to Week 72 ]
- Number of Participants Who Require Rescue Seizure Medication [ Time Frame: Week 24 and up to Week 72 ]
- Health-Related Quality of Life as Measured by the Care-Related Quality of Life of Informal Caregivers (CarerQoL-7D) Questionnaire [ Time Frame: Week 24 and up to Week 72 ]
- Number of Participants with Seizure Clusters [ Time Frame: Week 24 and up to Week 72 ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | up to 20 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04378075
Locations
Show 27 study locations
Sponsors and Collaborators
PTC Therapeutics
Investigators
| Study Director: | Vinay Penematsa, MD | PTC Therapeutics |
| Responsible Party: | PTC Therapeutics |
| ClinicalTrials.gov Identifier: | NCT04378075 |
| Other Study ID Numbers: |
PTC743-MIT-001-EP 2020-002100-39 ( EudraCT Number ) |
| First Posted: | May 7, 2020 Key Record Dates |
| Last Update Posted: | March 8, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by PTC Therapeutics:
|
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 |
Additional relevant MeSH terms:
|
Epilepsy Brain Diseases Drug Resistant Epilepsy Leigh Disease Diffuse Cerebral Sclerosis of Schilder Mitochondrial Diseases Syndrome Disease Pathologic Processes Central Nervous System Diseases Nervous System Diseases Metabolic Diseases |
Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Metabolism, Inborn Errors Genetic Diseases, Inborn Pyruvate Metabolism, Inborn Errors Carbohydrate Metabolism, Inborn Errors Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Leukoencephalopathies Demyelinating Diseases Autoimmune Diseases Immune System Diseases |