A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option

Study Overview
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Brief Summary
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The purpose of the study is to enable participants with pulmonary hypertension (PH) currently treated with study intervention(s) in a clinical study (parent studies [NCT03422328, NCT03904693 and NCT04565990]), to continue to benefit from the intervention after closure of the parent study in case they have no alternative means of access to the study intervention. This study will allow assessment of the long-term safety of each study intervention.

Official Title
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A Prospective, Open-label, Platform Study for Long-term Follow-up of Participants Using Study Intervention in Pulmonary Hypertension Parent Studies

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Macitentan
* Drug: Selexipag
* Drug: Macitentan/Tadalafil FDC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study Participant treated with oral macitentan or selexipag or fixed dose combination (FDC) of macitentan 10 milligrams (mg) and tadalafil 40 mg at the end of a sponsor parent study and: a) the indication of the parent study is included in the intervention-specific appendices (ISA) (pulmonary arterial hypertension [PAH] or chronic thromboembolic pulmonary hypertension [CTEPH] for adults, PAH for pediatric participants); b) participant has completed the parent study; c) no alternative means of access to study intervention (or equivalent approved therapy) have been identified; d) participant may continue to benefit from treatment with the study intervention; e) Participant is at least 18 years old for selexipag or macitentan/tadalafil FDC, and at least 2 years old for macitentan A female participant of childbearing potential must: a) have a negative urine or serum pregnancy test prior to first intake of study intervention; b) agree to perform monthly urine pregnancy test up to the end of the safety follow-up period; c) agree to follow contraceptive methods until 30 days after the last intake of the study intervention Exclusion Criteria: General: Participants prematurely discontinued from the study intervention in their parent study Female participant being pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study Planned or current treatment with another investigational treatment Macitentan-specific: Known allergies, hypersensitivity, or intolerance to macitentan or its excipients Hemoglobin less than (<) 80 grams per liter (g/L) Serum aspartate (AST) and/or alanine aminotransferases (ALT) greater than (>) 3* upper limit of normal (ULN) Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class (Child-Pugh score) should be fully assessed and documented in the source documents at screening Selexipag-specific: Known allergies, hypersensitivity, or intolerance to selexipag or its excipients Suspected or known pulmonary veno-occlusive disease (PVOD) Uncontrolled thyroid disease Severe coronary heart disease or unstable angina, myocardial infarction within the last 6 months, decompensated cardiac failure (if not under close medical supervision), severe arrhythmia, cerebrovascular events (for example, transient ischemic attack, stroke) within the last 3 months, or congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension (PH) Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class (Child-Pugh score) should be fully assessed and documented in the source documents at screening Macitentan/tadalafil FDC-specific: Known allergies, hypersensitivity, or intolerance to macitentan or tadalafil or their excipients Hemoglobin <80 g/L Serum aspartate (AST) and/or alanine aminotransferases (ALT) >3* ULN range Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class should be fully assessed and documented in the source documents at screening Severe renal impairment (estimated glomerular filtration rate [eGF]/creatinine clearance <30 milliliter per minute [mL/min])

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, open-label, extension study, with a platform-study design for long-term safety follow-up of participants using study intervention as in their respective pulmonary hypertension (PH) parent study (that is, pulmonary arterial hypertension [PAH] or chronic thromboembolic pulmonary hypertension [CTEPH]). Participants who have completed a parent study, that benefit from their study intervention maintenance and have no adequate alternative local treatment option (access to the study intervention or an equivalent approved therapy) will be enrolled in this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Macitentan<br>Participants who have completed a parent study, benefit from their study intervention maintenance and have no adequate alternative local treatment option will be enrolled in this study and will continue to receive study drug macitentan orally during the course of the study. For adult participants study visits will be scheduled every 6 months and for pediatric participants study visits will be scheduled every 3 months. The study includes on-site visits to collect efficacy and safety information until participant discontinuation/withdrawal, or the respective study intervention is made commercially available in the country/territory or an equivalent approved therapy becomes available, or the sponsor decides to terminate the study prematurely. | Drug: Macitentan<br>* Adult participants will receive oral dose of macitentan 10 milligrams (mg) tablet once daily. Children greater than or equal to (>=) 2 year to less than (<) 18 years will be given an oral macitentan dose tailored to their body weight, ensuring an equivalent level of systemic exposure as in adults.<br>* Other names: JNJ-67896062;|
| Experimental: Selexipag<br>Participants who have completed a parent study, benefit from their study intervention maintenance and have no adequate alternative local treatment option will be enrolled in this study and will continue to receive study drug selexipag orally during the course of the study. Study visits are scheduled every 6 months to collect efficacy and safety information until participant discontinuation/withdrawal, or the respective study intervention is made commercially available in the country/territory or an equivalent approved therapy becomes available, or the sponsor decides to terminate the study prematurely. | Drug: Selexipag<br>* Participant will receive oral dose of selexipag tablet twice daily at the dose strength corresponding to their maintenance dose at the end of their parent study. Available strengths: 200, 400, 600, 800, 1000, 1200, 1400 and 1600 micrograms.<br>* Other names: JNJ-67896049;|
| Experimental: Macitentan/Tadalafil FDC<br>Participants who have completed a parent study, benefit from their study intervention maintenance and have no adequate alternative local treatment option will be enrolled in this study and will continue to receive drug Macitentan and Tadalafil fixed dose combination (FDC) orally during the course of the study. Study visits are scheduled every 6 months to collect efficacy and safety information until participant discontinuation/withdrawal, or the respective study intervention is made commercially available in the country/territory or an equivalent approved therapy becomes available, or the sponsor decides to terminate the study prematurely. | Drug: Macitentan/Tadalafil FDC<br>* Participants will receive oral FDC of macitentan 10 mg and tadalafil 40 mg once daily during the course of the study as already received in the parent studies.<br>* Other names: JNJ-68150420;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Baseline until End of Study (EOS) (up to 57 months) | 
| Frequency of TEAEs Leading to Discontinuation | Frequency of TEAEs leading to discontinuation of study intervention will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Baseline until EOS (up to 57 months) | 
| Frequency of Serious Adverse Events (SAEs) | SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product and is medically important. | Baseline until EOS (up to 57 months) | 
| Frequency of Deaths | Frequency of deaths will be reported. | Baseline until EOS (up to 57 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Arterial Hypertension (PAH),, Chronic Thromboembolic Pulmonary Hypertension (CTEPH)