A study to see if it is safe and helpful to add Selexipag to other PAH medication in children and adolescents.
- Conditions
- Pulmonary Arterial HypertensionMedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2019-002817-21-BE
- Lead Sponsor
- Actelion Pharmaceuticals Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 237
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 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 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.
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
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 <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
18. Severe renal insufficiency (estimated creatinine clearance <30 mL/min or serum creatinine >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 in the best interest of the child (
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