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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04378075
Recruitment Status : Recruiting
First Posted : May 7, 2020
Last Update Posted : November 3, 2020
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

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 Drug: Vatiquinone Other: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : April 1, 2023


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:
  • PTC743
  • EPI-743

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 :
  1. 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 :
  1. Number of Disease-Related Hospital Days [ Time Frame: Week 24 and up to Week 72 ]
  2. Number of Participants with Occurrences or Recurrence of Status Epilepticus [ Time Frame: Week 24 and up to Week 72 ]
  3. Number of Participants with Disease-Related In-Patient Hospitalizations or Emergency Room Visits [ Time Frame: Week 24 and up to Week 72 ]
  4. Number of Disease-Related In-Patient Hospital Admissions or Emergency Room Visits [ Time Frame: Week 24 and up to Week 72 ]
  5. Change from Baseline to Week 72 in Total Seizure Frequency (All Types) per 28 Days [ Time Frame: Day 0, Week 24, Week 72 ]
  6. Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Motor Seizures [ Time Frame: Week 24 and up to Week 72 ]
  7. Percentage of Participants with ≥25%, ≥50%, ≥75%, and 100% Reduction in Total Seizures (All Types) [ Time Frame: Week 24 and up to Week 72 ]
  8. Number of Participants Who Require Rescue Seizure Medication [ Time Frame: Week 24 and up to Week 72 ]
  9. 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 ]
  10. 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.


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Ages Eligible for Study:   up to 18 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 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.
  • Consent to abstain from non-approved therapies for 30 days prior to the baseline visit (Day 0) and for the duration of the study.
  • Stable dose regimen of antiepileptic therapies 60 days prior to the baseline visit (Day 0).
  • Stable regimen of dietary supplements 30 days prior and, if on a ketogenic diet, stable ketogenic diet 90 days prior to the baseline visit (Day 0) and for duration of the study.
  • Electroencephalogram (EEG) at screening or historical EEG for diagnostic confirmation of seizures.

Exclusion Criteria:

  • Allergy to vatiquinone or sesame oil.
  • Aspartate transaminase (AST) or alanine transaminase (ALT) ≥2 × upper level of normal (ULN) at time of screening.
  • International normalized ratio (INR) ≥1.5 × 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.
  • Concomitant treatment with idebenone.
  • Ongoing treatment with cytochrome P450 (CYP) inhibitors such as itraconazole or 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 juice or St John's wort extract.
  • Pregnant or lactating participants or those sexually active participants who are unwilling to comply with proper birth control methods. Females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit (Day 0).

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


Contacts
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Contact: Patient Advocacy 1-866-562-4620 medinfo@ptcbio.com

Locations
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United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
Principal Investigator: Bruce Cohen, Dr.         
United States, Texas
University of Texas Health Science Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Niveditha Thakur, Dr.         
United States, Washington
Seattle Children's hospital Recruiting
Seattle, Washington, United States, 98105
Principal Investigator: Russel Saneto, Dr.         
Sponsors and Collaborators
PTC Therapeutics
Investigators
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Study Director: Vinay Penematsa, MD PTC Therapeutics
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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: November 3, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Epilepsy
Drug Resistant Epilepsy
Leigh Disease
Mitochondrial Diseases
Brain Diseases
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