Actelion announced the launch of a Phase 3 clinical trial evaluating the effectiveness of a pediatric formulation of Opsumit (macitentan) in delaying disease progression in children with pulmonary arterial hypertension (PAH).
Opsumit is an orally available endothelin receptor antagonist approved both in Europe and the U.S. for the treatment of PAH in adults.
The TOMORROW (pediaTric use Of Macitentan tO delay disease pProgRessiOn in PAH Worldwide) trial is a multicenter, controlled, and open-label assessment of the efficacy, safety and pharmacokinetics of Opsumit versus standard of care in children with PAH. If successful, it could lead to the first approved treatment for young PAH patients.
“Clinical studies in children come with big challenges, such as the influence of growth stage and body weight on the dosage scheme and on potential side effects. PAH is a rare disease in adults and even more so in children, so pediatric PAH physicians have to mostly rely on research data collected in adults when weighing up treatment options for their younger patients,” said Maurice Beghetti, head of Pediatric Cardiology at the University Hospital of Geneva, in a press release. “There is a significant medical need for showing the benefit of adequately adapted formulations and doses of PAH-specific medications in order to provide children with PAH with the most appropriate treatment. TOMORROW as a robust study assessing long-term treatment with the appropriate pediatric formulation of macitentan will deliver the sought-after data on all fronts.”
The primary efficacy endpoint of the TOMORROW trial is time to the first Clinical Event Committee-confirmed outcome event, including clinical worsening of PAH, hospitalization due to PAH, or atrial septostomy or Pott’s anastomosis.
The study will eventually enroll children between the ages of one month and 18 years from 20 different countries, but will begin with an evaluation of the drug’s pharmacokinetics in 40 children ages 2 to 18 to identify the best dose regimens for young patients. Opsumit’s pediatric formulation is as a water-dispersible tablet that is neutral in taste, and available in 0.5 mg, 2.5 mg and 5.0 mg doses.
“As there is no globally approved treatment for PAH in children, it was not possible to define a single unique treatment as reference drug or standard background. The design of the TOMORROW study will ensure that children receive the best available standard of care therapy or macitentan, a treatment that is well supported by long-term efficacy and safety data in adults,” said Dunbar Ivy, director of the Pediatric Pulmonary Hypertension Program at Children’s Hospital Colorado. “I welcome Actelion’s effort to broaden the pediatric knowledge base, which will help both physicians and their young PAH patients in the long term.”
Once the team has found the best dosage, enrolled patients will be randomized in a 1:1 ratio into two treatment groups, one receiving Opsumit and the other given standard of care treatment defined by local practice.
The trial is set up to last up to six years, with children being enrolled until 187 efficiency endpoint events have occurred.
“We take our leadership in PAH as a responsibility and have now committed to the first long-term, event-driven study in children with PAH using a pediatric formulation of macitentan,” concluded Jean-Paul Clozel, MD, chief executive officer of Actelion. “The design of the TOMORROW clinical trial allows the safe and comprehensive assessment of children over a long period of time.”