Pulmonary Arterial Hypertension MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Uptravi
Product Name: Selexipag
Product Code: JNJ-67896049 (ACT-293987)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SELEXIPAG
Current Sponsor code: JNJ-67896049 (ACT-29398
Sponsors
Actelion Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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, see 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 screening. 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 monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation. ? If sexually active, practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects 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. Are the trial subjects under 18? yes Number of subjects for this age range: 237 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Etiology 1. PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis. 2. PAH associated with Eisenmenger syndrome. 3. Moderate to large left-to-right shuntsa. 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. 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). Treatment and intervention 6. Previous exposure to Uptravi® (selexipag). 7. Treatment with prostacyclin (epoprostenol) or prostacyclin analogsa (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 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 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 11. Any PAH-related surgical intervention planned, or subjects listed for organ transplantation related to PAH. Medical history and co-morbidities 12. Known concomitant life-threatening disease with a life expectancy 221 µmol/L) 19 Severe coronary heart disease or unstable angina as assessed by the investigator 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 enrollment 24. Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to PH Pregnancy and breastfeeding 25. Pregnant, planning to become pregnant, or lactating Other categories 26. Known allergies, hypersensitivity, or intolerance to selexipag or its excipients (Selexipag IB) 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 28. Any condition for which, in the opinion of the investigator, participation would not be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether the addition of selexipag to Standard of Care treatment delays disease progression in children with PAH in comparison to placebo.;Secondary Objective: To assess the safety and tolerability of selexipag in children with PAH. To evaluate whether selexipag can delay hospitalization and death due to PAH worsening in children. To assess the trough plasma concentrations of selexipag and its active metabolite at steady-state in children with PAH. To explore the following safety and efficacy variables. To explore the Quality of Life (QoL). To explore the long-term safety, tolerability and efficacy of selexipag in children with PAH.;Primary end point(s): Time to disease progression from randomization up to 7 days after study treatment discontinuation.;Timepoint(s) of evaluation of this end point: Randomization up to 7 days after EOT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Treatment-emergent adverse events and serious adverse events. • Adverse events leading to premature discontinuation of study treatment • Treatment-emergent change in vital signs (systolic and diastolic arterial blood pressure and pulse rate) and body weight from baseline to all assessed time points • Growth: Treatment-emergent change in body weight and height from baseline to all assessed time points • Sexual maturation (Tanner stage) from baseline to all assessed time points up to 3 days after study treatment discontinuation • Treatment-emergent electrocardiogram abnormalities. • Treatment-emergent marked laboratory abnormalities at each time point of assessment. • Treatment emergent change from baseline in thyroid stimulating hormone over time. • Treatment emergent change in selected laboratory variables from baseline to all assessed time points. • Time to first Clinical Event Committee-confirmed hospitalization or death due to pulmonary arterial hypertension occurring from Randomization until 7 days after study treatment discontinuation. • Trough plasma concentration at steady-state of Selexipag and its metabolite ACT-333679 collected during the maintenance period. Exploratory • Time to death (all causes) occurring between Randomization and the Analysis Visit for each Analysis. • Time to first Clinical Event Committee-confirmed death due to pulmonary arterial hypertension occurring from randomization until 7 days after study treatment discontinuation. • Time to Clinical Event Committee-confirmed disease progression up to the Analysis Visit for each Analysis. • World Health Organization functional class III (yes/no) at each time point of assessment up to 7 days after study treatment discontinuation. • Change in World Health Organization functional class from baseline/enrollment to each time point of a | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Korea, Republic of, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United States, Vietnam
Contacts
Public ContactClinical Registry group
Janssen-Cilag International NV
Outcome results
None listed