Parent and/or Legal Guardian ICF and Adult patient ICF: 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 Hypertensio
- Conditions
- Pulmonary Arterial HypertensionTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- CTIS2022-501012-34-00
- Lead Sponsor
- Actelion Pharmaceuticals Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 213
1. Parent(s) (preferably both, if available, or as per local requirements, or their legally authorized representatives [LARs]) must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to allow the child to participate in the study. Assent is also required of children capable of understanding the nature of the study (typically 7 years of age and older) as described in Informed Consent Process in Section 10.4, Regulatory, Ethical, and Study Oversight Considerations., 2. Male and female participants between =2 and <18 years of age weighing =9 kg at Randomization., 3. PAH diagnosis confirmed by documented historical RHC performed at any time before participant's screening, and characterized by: • mPAP =25 mmHg, AND • Pulmonary arterial wedge pressure (PAWP) =15 mmHg (in the absence of pulmonary vein obstruction and/or significant lung disease, PAWP can be replaced by left atrial pressure or, in absence of mitral stenosis, by left ventricular end diastolic pressure) AND • Indexed PVR index (PVRi) >3 Wood units × m2., 4. PAH (WHO Group 1), including patients with Down syndrome, of the following etiologies: • Idiopathic PAH (IPAH). • Heritable PAH (HPAH). • PAH associated with congenital heart disease (PAH-aCHD): – PAH with coincidental CHD (ie, a small atrial septal defect, ventricular septal defect, or patent ductus arteriosus that does not itself account for the development of elevated PVR) and if approved by the BCAC, refer to Section 10.4). – Post-operative PAH (persisting / recurring/ developing =6 months after repair of CHD). • Drug or toxin-induced. • PAH associated with HIV., 5. WHO FC II and III., 6. Participants treated with at least 1 PAH-specific treatment, eg, an ERA and/or a PDE-5 inhibitor/soluble guanylate cyclase stimulator, provided that the treatment dose(s) has been stable for at least 3 months prior to first dose of study intervention., 7. A female participant of childbearing potential (for a definition refer to section 10.6) is eligible only if the following apply: Has a negative highly sensitive serum pregnancy test (ß-human chorionic gonadotropin) at screening and a negative urine pregnancy test at randomization. Agrees to undertake urine pregnancy tests every 4 weeks (+/-3 days) during the study and up to at least 30 days after study treatment discontinuation. If sexually active, practicing an effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies until 30 days after last dose of study intervention. Examples of acceptable methods of contraception are located in Section 10.6. It is the responsibility of the investigator to ensure appropriate counselling, including consultation with a specialist (if needed), to the subject and/or parent(s) / LAR(s) on the acceptable method of contraception. To ensure compliance, the study personnel must remind female participants of childbearing potential who are sexually active and their parent(s) / LAR(s) at each visit to use the methods of contraception defined for this study. These reminders must be documented in the source documents.
1. PAH due to portal hypertension, schistosomiasis, pulmonary venoocclusive disease, and/or pulmonary capillary hemangiomatosis., 25. Pregnant, planning to become pregnant, or lactating, 26. Known allergies, hypersensitivity, or intolerance to selexipag or its excipients (Selexipag IB), 10. Treatment with inhibitors of UGT1A3 and UGT2B7 (valproic acid, probenecid, and fluconazole) from 2 weeks prior to randomization until the last dose of study intervention + 3 days, 27. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease, 3. Moderate to large left-to-right shunts., 4. Cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, univentricular heart, or pulmonary atresia with ventricular septal defect, as well as subjects with Fontan-palliation., 5. Participants with PH due to lung disease and/or hypoxia or history of bronchopulmonary dysplasia. For participants with Down syndrome, exclusion of lung disease and hypoxia causing PH must be documented (eg, normal oxygen saturation in absence of history of lung disease, computed tomography scan, polysomnography, lung function tests)., 6. Previous exposure to Uptravi® (selexipag)., 7. Treatment with prostacyclin (epoprostenol) or prostacyclin analogs (ie, treprostinil, iloprost, beraprost) within 2 months prior to randomization or scheduled to receive any of these treatments during the study., 8. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before the planned first dose of study intervention or is currently enrolled in an investigational study, 18. Severe renal insufficiency (estimated creatinine clearance <30 mL/min or serum creatinine >221 µmol/L), 9. Treatment with strong and moderate inhibitors of CYP2C8 (eg, gemfibrozil, clopidogrel, deferasirox, teriflunomide) from 2 weeks prior to randomization until the last dose of study intervention +3 days, 11. Any PAH-related surgical intervention planned, or subjects listed for organ transplantation related to PAH., 12. Known concomitant life-threatening disease with a life expectancy <12 months, 13. History or current suspicion of intussusception or ileus or gastrointestinal obstruction, per the investigator's judgment, 14. Uncontrolled thyroid disease, per the investigator's judgment, 15. Hemoglobin or hematocrit <75% of the lower limit of normal range, 16. Known severe or moderate hepatic impairment, ie, Child-Pugh Class B or C, 17. Clinical signs of hypotension that, in the investigator's judgment, would preclude initiation of a PAH-specific therapy, 28. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the child (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments, 19 Severe coronary heart disease or unstable angina as assessed by the investigator, 2. PAH associated with Eisenmenger syndrome., 20. Myocardial infarction within the last 6 months prior to enrollment, 21. Decompensated cardiac failure if not under close supervision, 22. Severe arrhythmias as assessed by the investigator, 23. Cerebrovascular events (eg, transient ischemic attack, stroke) within the last 3 months prior to first dose of study intervention., 24. Congenital or acquired valvular defects
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method