MIT-E: Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease (MD) Subjects with Refractory Epilepsy
Abstract number :
3.413
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2232973
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:29 AM
Authors :
Vinay Penematsa, MD – PTC Therapeutics; Vij Senthilnathan, MS – PTC Therapeutics; Bruce Cohen, MD, FAAN – Akron Children’s Hospital; Kei Murayama, MD, PhD – Chiba Children’s Hospital; Nicole Chemaly, MD – Hôpital Necker-Enfants Malades; Mary Kay Koenig, MD – Children’s Memorial Hermann Hospital; Robert McFarland, MA, MBBS, PhD, MRCP, FRCPCH – Great North Children’s Hospital, Newcastle upon Tyne; Fernando Scaglia, MD, FACMG – The University of Texas McGovern Medical School; Russell Saneto, DO, PhD – Seattle Children’s Hospital; Hideaki Shiraishi, MD, DMS – Hokkaido University Hospital; Lin Min, PhD – PTC Therapeutics; Jonathan Cherry, PhD – PTC Therapeutics; Matthew Klein, MD, MS, FACS – PTC Therapeutics; Peter Giannousis, PhD – PTC Therapeutics; Lee Golden, MD – PTC Therapeutics
This is a Late Breaking abstract
Rationale: Epilepsy occurs in 35-60% of all patients with mitochondrial disease (MD), which is often refractory to conventional antiepileptic medications.1 Defects in genes affecting mitochondrial proteins often affect oxidative phosphorylation pathways, resulting in energy dysregulation and cellular dysfunction which contributes to mitochondrial disease associated seizures.1 Vatiquinone is a novel inhibitor of 15-lipoxygenase that prevents lipid peroxidation and subsequent oxidative stress,1 and has been reported to reverse disease progression in clinical studies of patients with MD.2,3 MIT-E is a phase 2/3 randomized, placebo-controlled study of vatiquinone for the treatment of mitochondrial disease associated seizures.
Methods: Targeted enrollment is approximately 60 subjects with MD and associated refractory epilepsy will be enrolled (defined as those who were unsatisfactorily treated with ≥ 2 antiepileptics). Subjects will be randomized 1:1 to receive either vatiquinone at a dose of 15 mg/kg if body weight < 13 kg, and 200 mg if body weight ≥ 13 kg, three times daily (TID), or placebo TID for 24 weeks. The primary endpoint is percent change from baseline in frequency of observable motor seizures. Key secondary endpoints include the number of disease-related hospitalization days, occurrence or recurrence of status epilepticus, number and percent of patients with disease-related inpatient hospitalization/emergency room visits and health-related quality of life. Subjects completing the 24-week blinded phase will be eligible for a 48-week open-label treatment phase. There will be a follow up 30 days post last study drug administration or termination visit, whichever is later._x000D_
Key inclusion criteria are a genetic confirmation of inherited MD with associated epilepsy phenotype, stable dose regimen of antiepileptic therapies 30 days prior to screening visit, and electroencephalogram for diagnostic confirmation of seizures. Key exclusion criteria are alanine transaminase or aspartate transaminase ≥ 3× upper level of normal (ULN) at screening, coagulation function measured by international normalized ratio (prothrombin time and partial thromboplastin time) > ULN at screening, and serum creatinine ≥ 1.5× ULN at screening.
Results: The MIT-E study is ongoing with results from the placebo-controlled phase expected to be available in the first quarter of 2023. Baseline patient demographics will be presented at the 2022 AES Annual Meeting.
Conclusions: The MIT-E study will provide data on the effect of vatiquinone on reduction in observable motor seizure frequency in subjects with genetically confirmed MD.
Funding: Funding was provided by PTC Therapeutics, Inc.
Anti-seizure Medications