A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group Study with Open-Label Extension Period to Assess the Efficacy and Safety of Selexipag as Add-On Treatment to Standard of Care in Children Aged ≥2 to <18 years with Pulmonary Arterial Hypertension

The primary objective of this study is to evaluate whether the addition of **selexipag** to standard of care treatment delays disease progression in children with **Pulmonary Arterial Hypertension** (PAH) compared to placebo. This is clinically relevant as PAH is a severe condition that can lead to significant morbidity and mortality, and finding effective treatments to slow disease progression is crucial for improving patient outcomes.

The clinical trial involves a total of **140 participants** diagnosed with **Pulmonary Arterial Hypertension** (PAH). The study population includes both male and female subjects, aged between 2 and 18 years, with a minimum weight of 9 kg at the time of randomization. Participants were selected based on a confirmed diagnosis of PAH, characterized by specific hemodynamic criteria, and are required to be on stable PAH-specific treatment regimens, such as endothelin receptor antagonists or phosphodiesterase-5 inhibitors, for at least three months prior to the study. The trial includes a vulnerable population, as it involves children, and requires informed consent from parents or legally authorized representatives, with assent from children capable of understanding the study. Lifestyle considerations such as diet and physical activity are not specified, but female participants of childbearing potential must adhere to strict contraceptive measures throughout the study duration. The trial aims to assess the efficacy of adding selexipag to standard care in delaying disease progression compared to a placebo.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group study with an open-label extension period. The primary objective is to evaluate the efficacy and safety of **selexipag** as an add-on treatment to the standard of care in children aged 2 to less than 18 years with **pulmonary arterial hypertension** (PAH). The trial is expected to run from February 27, 2020, to January 10, 2028, with the primary endpoint being the time to disease progression from randomization up to 7 days after study treatment discontinuation.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and a confirmed diagnosis of PAH. Following randomization, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. The study will conclude with an end-of-study visit, where final assessments will be conducted. The expected length of participant involvement is up to 96 weeks, with conditions for early termination including significant adverse events or withdrawal of consent.

Key elements of the research methodology include the use of a placebo group to compare against the active treatment group, ensuring the study's validity and reliability. The trial will involve the administration of **selexipag** in the form of film-coated tablets, with a maximum daily dose of 3200 micrograms. Participants will be monitored for adherence to the study protocol, and any deviations may result in early termination from the study. The trial's design and procedures are structured to ensure the collection of robust data to assess the potential benefits of **selexipag** in delaying disease progression in the pediatric population with PAH.

The clinical trial involves the administration of **Selexipag**, a selective and long-acting non-prostanoid agonist of the prostacyclin receptor (IP receptor). The experimental medication, identified by the sponsor product code JNJ-67896049, is provided in the form of a film-coated tablet. The active substance, Selexipag, is chemically derived and manufactured by Actelion Pharmaceuticals Ltd. The medication is administered orally, with a maximum daily dose of 3200 µg microgram(s) and a treatment period extending up to 96 weeks. The trial includes both standard and pediatric formulations of Selexipag, ensuring appropriate dosing for children aged ≥2 to <18 years with pulmonary arterial hypertension (PAH).

In addition to the experimental treatment, the study utilizes **Bosentan** as a comparator treatment. Bosentan is provided in the form of dispersible tablets, marketed under the name Tracleer 32 mg dispersible tablets by Janssen-Cilag International NV. The pharmaceutical form is an oral solution, and the maximum daily dose is 240 mg milligram(s). The administration route is oral, and the treatment period is consistent with the experimental medication, lasting up to 96 weeks. Bosentan serves as a standard-of-care therapy in the trial, allowing for a comprehensive evaluation of Selexipag's efficacy and safety as an add-on treatment.

Placebo treatments, identified as PL1, PL2, PL3, and PL4, are also employed in the study to maintain the double-blind design. These placebos do not have specified pharmaceutical forms, active substances, or administration routes. They are used to ensure unbiased assessment of the experimental medication's effects compared to no active treatment. Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the protocol and accurate evaluation of treatment outcomes.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the time to disease progression from randomization up to 7 days after study treatment discontinuation. This endpoint is designed to measure the effectiveness of **selexipag** as an add-on treatment to the standard of care in children aged 2 to less than 18 years with Pulmonary Arterial Hypertension (PAH). The trial is structured as a randomized, multicenter, double-blind, placebo-controlled, parallel-group study with an open-label extension period.