A registration-directed phase 2/3 clinical trial (NCT04378075) to evaluate vatiquinone (PTC743; PTC Therapeutics, South Plainfield, NJ) in individuals with mitochondrial epilepsy (MIT-E) has begun. The Food and Drug Administration (FDA) has granted vatiquinone orphan drug designation and pediatric rare disease designation for MIT-E.
In earlier trials, vatiquinone, a 15-lipoxygenase inhibitor has decreased seizure frequency and seizure-related morbidity. Inhibition of 15-lipoxygenase affects the oxidative stress and inflammatory response pathways thought to underpin MIT-E pathology.
The phase 2/3 trial in MIT-E is a randomized placebo-controlled study evaluating vatiquinone in approximately 60 participants with genetically confirmed MIT-E. Enrolled participants will be in a 1-month run-in phase to ensure a minimum number of observable motor seizures. Participants who meet that threshold will be enrolled in a 6-month parallel arm placebo-controlled phase to test whether vatiquinone treatment reduces motor seizure frequency relative to the run-in phase more than placebo treatment does. Secondary endpoints include the occurrence of status epilepticus, number of hospitalizations, rescue medication use, and caregiver burden.
"We are excited to initiate this registrational clinical trial to evaluate the first indication for vatiquinone that was identified from our Bio-e platform," said Stuart W. Peltz, PhD, chief executive officer, PTC Therapeutics, Inc. "As a devastating and highly fatal pediatric disorder with no approved treatment options, mitochondrial epilepsy represents an area of significant unmet need. Vatiquinone has been evaluated in over 500 patients to date, and in clinical studies it has demonstrated effects in resolving refractory status epilepticus, decreasing seizure frequency and seizure-related morbidity in certain patients. We look forward to advancing this compound for patients who are clearly in need of treatment."
Cyrus A. Raji, MD, PhD; Somayeh Meysami, MD; and Mario F. Mendez, MD, PhD
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Adam M. Staffaroni, PhD; Elena Tsoy, PhD; Jack Taylor, BS; Adam L. Boxer, MD, PhD; and Katherine L. Possin, PhD