Chronic Thromboembolic Pulmonary Hypertension, inoperable or persistent/recurrent MedDRA version: 21.1 Level: LLT Classification code 10068739 Term: Chronic thromboembolic pulmonary hypertension System Organ Class: 100000004855
Conditions
Sponsors
Actelion Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated Informed Consent Form. 2. Male and female subjects =18 (or the legal age of consent in the jurisdiction in which the study is taking place) and =85 years old at Screening (Visit 1). 3. Subjects with diagnosis of CTEPH and inoperability confirmed by the corresponding adjudication committee (AC; country-specific adjudication committee [CSAC] or central adjudication committee [CAC]), defined as one of the following options: a) Inoperable CTEPH (ie, technically non-operable) with: – Diagnosis of CTEPH based on at least two of the following assessments performed in the 14-month period prior to randomization (Visit 2): ventilation/perfusion (V/Q) scan; pulmonary angiography (PA); computed tomography pulmonary angiogram (CTPA) and/or magnetic resonance angiography (MRA). – RHC (and LHC, if needed) 1 performed at least 90 days after start of full anticoagulation showing: PVR at rest = 400 dyn.sec/cm5 or = 5 Wood units for the hemodynamic cohort and PVR at rest = 300 dyn.sec/cm5 or =3.75 Wood units for the non-hemodynamic cohort; (mPAP) = 25 mmHg; Pulmonary arterial wedge pressure (PAWP) = 15 mmHg or, if not available or unreliable, a left ventricular end diastolic pressure (LVEDP) = 15 mmHg. b) Persistent/recurrent CTEPH after BPA, with: – Diagnosis of CTEPH based on at least one of the following assessments performed in the 14-month period prior to randomization (Visit 2) and after last interventional (BPA) treatment: V/Q scan, PA, CTPA or MRA. – RHC (and LHC, if needed) 1 performed at least 90 days after last interventional (BPA) treatment and at least 90 days after start of full anticoagulation, showing: PVR at rest = 400 dyn.sec/cm5 or = 5 Wood units for the hemodynamic cohort and PVR at rest = 300 dyn.sec/cm5 or =3.75 Wood units for the non-hemodynamic cohort; mPAP = 25 mmHg; PAWP = 15 mmHg, or, if not available or unreliable, an LVEDP = 15 mmHg. c) Persistent/recurrent CTEPH after PEA (including PEA followed by BPA) with: – Diagnosis of CTEPH based on at least one of the following assessments performed in the 14-month period prior to randomization (Visit 2) and after last surgical (PEA) or interventional (BPA) treatment: V/Q scan, PA, CTPA or MRA. -RHC (and LHC, if needed) 1 performed at least 90 days after last surgical (PEA) or interventional (BPA) treatment and at least 90 days after start of full anticoagulation, showing: PVR at rest = 400 dyn.sec/cm5 or 5 Wood units for the hemodynamic cohort and PVR at rest = 300 dyn.sec/cm5 or =3.75 Wood units for the non-hemodynamic cohort; mPAP = 25 mmHg; PAWP = 15 mmHg, or, if not available or unreliable, an LVEDP = 15 mmHg. 4. PH in WHO FC I–IV. 5. Subject able to perform the 6MWT with a minimum distance of 100 m and a maximum distance of 450 m at screening visit (Visit 1). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 182 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 98
Exclusion criteria
Exclusion criteria: General exclusion criteria: 1. Planned or current treatment with another investigational treatment up to 3 months prior to randomization. 2. 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. Known concomitant life-threatening disease with a life expectancy < 12 months. Exclusion criteria related to the disease: 4. Planned BPA within 26 weeks after randomization. 5. Change in dose or initiation of new PH-specific therapy within 90 days prior to the baseline RHC (and LHC, if needed) qualifying for enrollment for the hemodynamic cohort and within 90 days prior to randomization (Visit 2) for the non-hemodynamic cohort. 6. Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e., selexipag/Uptravi) within 90 days prior to randomization (Visit 2), except those given at vasodilator testing during RHC. 7. Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC (and LHC, if needed). Exclusion criteria related to comorbidities: 8. Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc). 9. Other as per selexipag Summary of Product Characteristics (SmPC). Exclusion criteria related to selexipag use: 10. As per selexipag Summary of Product Characteristics (SmPC).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the effect of selexipag on pulmonary vascular resistance (PVR) versus placebo in subjects with inoperable CTEPH (i.e., technically non-operable) and persistent/recurrent CTEPH after surgical (pulmonary endarterectomy [PEA]) and/or interventional (balloon pulmonary angioplasty [BPA]) treatment at Week 20. ;Secondary Objective: The secondary objectives of the study are to evaluate the effects of selexipag versus placebo on: • Exercise capacity. • Time to clinical worsening (TTCW). • All-cause death or hospitalizations related to PH worsening. • WHO FC. • Patient-reported outcomes (PROs). • Dyspnea. • N-terminal pro b-type natriuretic peptide (NT-proBNP).;Primary end point(s): The primary efficacy endpoint of this study is the pulmonary vascular resistance (PVR) at Week 20, assessed at rest, within 2–5 hours post-dose, expressed as percent of baseline PVR.;Timepoint(s) of evaluation of this end point: Assessed at rest in screening period (Day -60 to Day -14; baseline) and assessed at rest within 2–5 hours post-dose at Week 20 during treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in 6-minute walk distance (6MWD) to Week 26 (key secondary endpoint). 2. TTCW (according to the CHMP definition, key secondary endpoint), defined as at least one of the following components confirmed by the CEC, when applicable: – All-cause death – Non-planned PH-related hospitalization – PH-related deterioration identified by at least one of the foolowing: Increase from baseline in WHO FC; Deterioration by at least 15% in exercise capacity, as measured by the 6MWD; New signs or symptoms of right heart failure, defined as a reported AE with one of the preferred terms "CTEPH”, “pulmonary hypertension”, “right ventricular failure”, “right ventricular dysfunction” and/or “acute right ventricular failure”); The investigation of a composite endpoint that reflects the TTCW has been encouraged by the European Medicines Agency 3. All-cause death or hospitalizations related to PH worsening. 4. Proportion of subjects with improvement in WHO FC from baseline to Week 26. 5. Change from baseline to Week 26 in PAH-SYMPACT™ scores cardiopulmonary symptom domain and cardiovascular symptom domain. 6. Change from baseline to Week 26 in Borg dyspnea index (BDI)/Borg CR10®. 7. Change from baseline to Week 26 in NT-proBNP.;Timepoint(s) of evaluation of this end point: 1. Week 26 2. end of double blind treatment period 3. end of double blind treatment period 4. Week 26 5. Week 26 6. Week 26 7. Week 26 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Poland, Portugal, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Disclosure Desk
Actelion Pharmaceuticals Ltd
Outcome results
None listed