Clinical Trials List
Protocol NumberAC-065B302
NCT Number(ClinicalTrials.gov Identfier)NCT03689244
2019-07-01 - 2022-02-28
Phase III
Recruiting4
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Group-sequential, Adaptive, Phase 3 Study With Open-label Extension Period 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 and/or Interventional Treatment Chronic Thromboembolic Pulmonary Hypertension
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Trial Applicant
Johnson & Johnson
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Sponsor
Janssen Research & Development, LLC
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Shih-Sheng Chang Division of Cardiovascular Diseases
- Chung-Ho Hsu Division of Cardiovascular Diseases
- 張志斌 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Po-Sheng Chen Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- YEN-HUNG LIN Division of Thoracic Surgery
- SHUENN-WEN KUO Division of Thoracic Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Chronic Thromboembolic Pulmonary Hypertension
Objectives
Primary objective
The primary objective of the study is to evaluate the effect of selexipag on PVR versus
placebo in subjects with inoperable CTEPH (i.e., technically non-operable) and
persistent/recurrent CTEPH after surgical (PEA) and/or interventional (BPA) treatment at
Week 20.
Secondary objectives
The secondary objectives of the study are to evaluate the effects of selexipag versus placebo
on:
• Exercise capacity.
• Rate of death or hospitalizations related to PH worsening.
• Time to clinical worsening.
• WHO FC.
• Patient-reported outcomes (PROs).
• Dyspnea.
• N-terminal pro b-type natriuretic peptide (NT-proBNP).
Test Drug
Selexipag(ACT-293987)
Active Ingredient
Selexipag(ACT-293987)
Dosage Form
tablet
Dosage
200
Endpoints
Primary efficacy endpoint(s)
The primary efficacy endpoint of this study is the PVR at Week 20, assessed at rest, within
2–5 hours post-dose, expressed as percent of baseline PVR.
Secondary efficacy endpoints
The secondary efficacy endpoints of this study are:
• Change from baseline in 6MWD to Week 26 (key secondary endpoint).
• Rate of all-cause death or hospitalizations related to PH worsening up to Week 52.
• Time to clinical worsening (according to the CHMP definition) up to Week 52, defined
as at least one of the following components:
– All-cause death
– Non-planned PH-related hospitalization
– PH-related deterioration identified by at least one of the following:
o Increase in WHO FC;
o Deterioration by at least 15% in exercise capacity, as measured by the
6MWD;
o 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”.
The investigation of a composite endpoint that reflects the time to clinical worsening
has been encouraged by the European Medicines Agency [EMEA 2008].
• Proportion of subjects with improvement in WHO FC from baseline to Week 26.
• Change from baseline to Week 26 in PAH-SYMPACT™ scores.
• Change from baseline to Week 26 in Borg dyspnea index (BDI).
• Change from baseline to Week 26 in NT-proBNP.
The primary efficacy endpoint of this study is the PVR at Week 20, assessed at rest, within
2–5 hours post-dose, expressed as percent of baseline PVR.
Secondary efficacy endpoints
The secondary efficacy endpoints of this study are:
• Change from baseline in 6MWD to Week 26 (key secondary endpoint).
• Rate of all-cause death or hospitalizations related to PH worsening up to Week 52.
• Time to clinical worsening (according to the CHMP definition) up to Week 52, defined
as at least one of the following components:
– All-cause death
– Non-planned PH-related hospitalization
– PH-related deterioration identified by at least one of the following:
o Increase in WHO FC;
o Deterioration by at least 15% in exercise capacity, as measured by the
6MWD;
o 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”.
The investigation of a composite endpoint that reflects the time to clinical worsening
has been encouraged by the European Medicines Agency [EMEA 2008].
• Proportion of subjects with improvement in WHO FC from baseline to Week 26.
• Change from baseline to Week 26 in PAH-SYMPACT™ scores.
• Change from baseline to Week 26 in Borg dyspnea index (BDI).
• Change from baseline to Week 26 in NT-proBNP.
Inclution Criteria
Main Inclusion Criteria:
Signed and dated informed consent form
Male and female subjects from greater than or equal to (>) 18 (or the legal age of consent in the jurisdiction in which the study is taking place) and less then or equal to (<=85) years old at Screening (Visit 1)
With established diagnosis of inoperable CTEPH (i.e., technically non-operable) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA), as confirmed by the corresponding adjudication committee
With pulmonary hypertension (PH) in WHO FC I-IV.
Subject able to perform the 6-minute walk test (6MWT) with a minimum distance of 100 m and a maximum distance of 450 m at screening visit.
Women of childbearing potential must have a negative pregnancy test at screening and randomization and must agree to undertake monthly urine pregnancy tests, and to use a reliable method of birth control from screening visit up to at least 30 days after study treatment discontinuation. If a hormonal contraceptive is chosen it must be taken for at least 1 month prior to randomization.
Signed and dated informed consent form
Male and female subjects from greater than or equal to (>) 18 (or the legal age of consent in the jurisdiction in which the study is taking place) and less then or equal to (<=85) years old at Screening (Visit 1)
With established diagnosis of inoperable CTEPH (i.e., technically non-operable) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA), as confirmed by the corresponding adjudication committee
With pulmonary hypertension (PH) in WHO FC I-IV.
Subject able to perform the 6-minute walk test (6MWT) with a minimum distance of 100 m and a maximum distance of 450 m at screening visit.
Women of childbearing potential must have a negative pregnancy test at screening and randomization and must agree to undertake monthly urine pregnancy tests, and to use a reliable method of birth control from screening visit up to at least 30 days after study treatment discontinuation. If a hormonal contraceptive is chosen it must be taken for at least 1 month prior to randomization.
Exclusion Criteria
Main Exclusion Criteria:
Planned or current treatment with another investigational treatment up to 3 months prior to randomization.
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.
Known concomitant life-threatening disease with a life expectancy < 12 months.
Planned balloon pulmonary angioplasty within 26 weeks after randomization.
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
Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e., selexipag) within 90 days prior to randomization (visit 2) except those given at vasodilator testing during RHC
Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC (and LHC, if needed)
Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc).
Any other criteria as per selexipag Summary of Product Characteristics (SmPC).
Exclusion criteria related to comorbidities: severe coronary heart disease or unstable angina as assessed by the investigator; mocardial infarction within the last 6 months prior to or during Screening; decompensated cardiac failure if not under close supervision; severe arrhythmias as assessed by the investigator; cerebrovascular events (example transient ischemic attack, stroke) within the last 3 months prior to or during screening; congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension. (PH); known or suspicion of pulmonary veno-occlusive disease
Planned or current treatment with another investigational treatment up to 3 months prior to randomization.
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.
Known concomitant life-threatening disease with a life expectancy < 12 months.
Planned balloon pulmonary angioplasty within 26 weeks after randomization.
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
Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e., selexipag) within 90 days prior to randomization (visit 2) except those given at vasodilator testing during RHC
Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC (and LHC, if needed)
Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc).
Any other criteria as per selexipag Summary of Product Characteristics (SmPC).
Exclusion criteria related to comorbidities: severe coronary heart disease or unstable angina as assessed by the investigator; mocardial infarction within the last 6 months prior to or during Screening; decompensated cardiac failure if not under close supervision; severe arrhythmias as assessed by the investigator; cerebrovascular events (example transient ischemic attack, stroke) within the last 3 months prior to or during screening; congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension. (PH); known or suspicion of pulmonary veno-occlusive disease
The Estimated Number of Participants
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Taiwan
7~10 participants
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Global
400 participants
