A clinical study to assess the efficacy and safety of selexipag as an add-on to standard of care therapy in subjects with inoperable or persistent/recurrent, after surgical treatment and/or Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

A multicenter, randomized, double-blind, placebo-controlled, parallelgroup, group-sequential, adaptive, Phase 3 study with open-label extension period to assess the efficacy and safety of selexipag as an addon to standard of care therapy in subjects with inoperable or persistent/recurrent after surgical and/or interventional treatment Chronic Thromboembolic Pulmonary Hypertension. - SELECT

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-002823-41-GB

Enrollment

280

Registered

2018-09-18

Start date

2019-03-25

Completion date

Unknown

Last updated

2020-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

Trade Name: Uptravi Product Name: Selexipag Product Code: ACT-293987 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: SELEXIPAG Current Sponsor code: ACT-293987 Concentration unit: µg micr

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Signed and dated ICF. 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,; Mean pulmonary artery pressure (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, and deemed inoperable 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 surgery 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 = 25mmHg; 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 randomisation (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. Symptomatic 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 channelblockers 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 treatment (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.	—

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 treatment (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 (key secondary endpoint), where clinical worsening is defined (adapted from the CHMP definition [EMEA 2008]) 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 following: • Increase from baseline in WHO FC4; • Deterioration from baseline by at least 15% in exercise capacity, as measured by the 6MWD4; • New or worsening of signs or symptoms of right heart failure, defined as a reported AE with one of the following preferred terms: "CTEPH", "pulmonary hypertension", "right ventricular failure", "right ventricular dysfunction" and "acute right ventricular failure". 3. All-cause death or hospitalizations related to PH worsening. 4. Improvement in WHO FC from baseline to Week 26. 5. Change from baseline to Week 26 in Pulmonary arterial hypertensionsymptoms and impact questionnaire (PAH-SYMPACT®) cardiopulmonary symptoms domain and cardiovascular symptoms 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	—

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 (key secondary endpoint), where clinical worsening is defined (adapted from the CHMP definition [EMEA 2008]) 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 following: • Increase from baseline in WHO FC4; • Deterioration from baseline by at least 15% in exercise capacity, as measured by the 6MWD4; • New or worsening of signs or symptoms of right heart failure, defined as a reported AE with one of the following preferred terms: "CTEPH", "pulmonary hypertension", "right ventricular failure", "right ventricular dysfunction" and "acute right ventricular failure". 3. All-cause death or hospitalizations related to PH worsening. 4. Improvement in WHO FC from baseline to Week 26. 5. Change from baseline to Week 26 in Pulmonary arterial hypertensionsymptoms and impact questionnaire (PAH-SYMPACT®) cardiopulmonary symptoms domain and cardiovascular symptoms 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, Czechia, 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 Registry group

Janssen-Cilag International NV

ClinicalTrialsEU@its.jnj.com+31 71 5242166

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026