E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
sarcoidosis-associated pulmonary hypertension (SAPH) |
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E.1.1.1 | Medical condition in easily understood language |
Elevated pressure in lung vessels due to sarcoidosis (i.e. sarcoidosis-associated pulmonary hypertension [SAPH]) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037400 |
E.1.2 | Term | Pulmonary hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of selexipag versus placebo on pulmonary vascular resistance (PVR) in participants with sarcoidosis-associated pulmonary hypertension (SAPH) up to Week 26. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. 2. Male or female. 3. 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age, inclusive, at Screening. 4. Confirmed diagnosis of sarcoidosis as per American Thoracic Society (ATS) criteria (Crouser 2020: Statement on sarcoidosis 1999). 5. Sarcoidosis-associated precapillary PH, confirmed by RHC (at rest) within 90 days prior to randomization: a. PVR ≥320 dyn*sec/cm5 (≥4.0 Wood units) b. Mean pulmonary arterial pressure (mPAP) ≥25 mm Hg c. Pulmonary artery wedge pressure (PAWP) ≤15 mm Hg, or if not available or unreliable, a left ventricular end diastolic pressure (LVEDP) ≤15 mm Hg. 6. PH severity according to modified WHO FC II–IV at Screening and randomization; participants of WHO FC IV must be in a stable condition and able to perform a 6MWT. 7. Criterion modified per Amendment 2. 7.1 Either not receiving PH-specific treatment, or receiving PH-specific oral monotherapy (ie, riociguat or PDE5i or ERA); if on oral PH-specific monotherapy treatment has to be stable (ie, no introduction of new therapies or changes in dose) for at least 90 days prior to both the RHC qualifying for enrollment and randomization. 8. Criterion modified per Amendment 2. 8.1 Stable sarcoidosis treatment regimen, ie, no new specific anti-inflammatory treatment for sarcoidosis for at least 90 days, and stable dose(s) for at least 30 days prior to both the RHC qualifying for enrollment and randomization. 9. Criterion modified per Amendment 3 9.1 6MWD ≥50m both at Screening and at the time of randomization. NOTE: Participants can use their usual walking aids during the test (eg, cane, crutches). The same walking aid should be used for all 6MWTs. Walkers are not allowed. 10. Criterion modified per Amendment 3 10.1 FVC>50% and FEV1>50% of predicted at Screening. 11. Criterion modified per Amendment 3 11.1 DLCO ≥40% of predicted. If DLCO <40% of predicted, the extent of emphysema should not be greater than that of fibrosis as assessed by high resolution CT scan. 12. For patients enrolled or planned to be enrolled in a cardio-pulmonary rehabilitation program based on exercise training, one of the following must apply: • In the maintenance phase of the program at the time of randomization with no plans to stop the program until Week 39, or • Start of the cardio-pulmonary rehabilitation program based on exercise training is planned after Week 39. 13. A woman must be a. Not of childbearing potential b. Of childbearing potential and o Have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG) at Screening and a negative urine pregnancy test at randomization. o Agree to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study intervention discontinuation. o Practicing an acceptable method of contraception and agreeing to remain on an acceptable method while receiving study intervention and until 30 days after last dose of study intervention. 14. Criterion modified per Amendment 3; 14.1 A woman only using hormonal contraceptives must have been using this method for at least 30 days prior to randomization. 15. Willing and able to adhere to the lifestyle restrictions specified in Section 5.3. |
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E.4 | Principal exclusion criteria |
1. PH due to left heart disease (PAWP >15 mm Hg). 2. PH due to compression of pulmonary arteries and/or pulmonary veins. 3. History of left heart failure (LHF) as assessed by the investigator including cardiomyopathies and cardiac sarcoidosis, with a left ventricular ejection fraction (LVEF) <40%. 4. Severe coronary heart disease (CHD) or unstable angina as assessed by the investigator. 5. Myocardial infarction within the last 6 months prior to or during Screening. 6. Criterion modified per Amendment 2. 6.1 Decompensated cardiac failure not receiving optimal medical treatment according to local guidelines. 7. Arrhythmias assessed as severe by the investigator. 8. Criterion modified per Amendment 2. 8.1 Criterion modified per Amendment 3 8.2 Participants who either are planning to receive an implantable cardioverter defibrillator (ICD) or who already have one that has delivered shock therapy any time in the previous 1 year prior to Day 1. Participants with ICD are eligible if no shock therapy has been delivered in the previous 1 year prior to Day 1. 9. Cerebrovascular events (eg, transient ischemic attack, stroke) within the last 90 days prior to or during Screening. 10. Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to PH. 11. Overt features of pulmonary veno-occlusive disease (PVOD). 12. Significant emphysema as assessed by the investigator. 13. Criterion modified per Amendment 2. 13.1 Known and documented severe hepatic impairment (eg. Child-Pugh Class C). 14. Severe renal failure (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 or serum creatinine >2.5 mg/dL) based on central laboratory results from the Screening blood sample. 15. Criterion modified per Amendment 2. 15.1 Treatment with prostacyclin, prostacyclin analogues or IP receptor agonists (ie, selexipag) within 90 days prior to randomization and/or prior to the RHC qualifying for enrollment, except those given at vasodilator testing during RHC. 16. Included on a lung transplant list or planned to be included until Visit 6 / Week 39. 17. Known or suspected uncontrolled thyroid disease as per investigator judgment. 18. Treatment with moderate inducers of CYP2C8, eg rifampicin or strong inhibitors of CYP2C8, eg, gemfibrozil at or within 14 days prior to randomization. 19. Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to RHC qualifying for enrollment. 20. SBP <90 mmHg at Screening or at randomization. 21. Known allergies, hypersensitivity, or intolerance to selexipag or its excipients (refer to IB selexipag). 22. Planned or current treatment with another investigational intervention up to 90 days prior to randomization. 23. Criterion deleted per Amendment 3 24. Any condition for which, in the opinion of the investigator, participation would not be in the best interests of the participant (eg, compromise well-being), or that could prevent, limit, or confound the protocol-specified assessments. 25. Criterion modified per Amendment 3 25.1 Any acute or chronic impairment that may influence the ability to comply with study requirements such as to perform RHC, a reliable and reproducible 6MWT, or lung function tests. 26. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator. 27. Pregnant, breast-feeding, or planning to become pregnant while enrolled in this study of within 30 days after the last dose of study intervention.
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E.5 End points |
E.5.1 | Primary end point(s) |
• PVR on study intervention up to Week 26 expressed as percent of the baseline value. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 to 5 hours post-dose at week 26 |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
United States |
France |
Netherlands |
Spain |
Germany |
Italy |
Belgium |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |