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A Study to Find Out if Selexipag is Effective and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension When the Disease is Inoperable or Persistent/Recurrent After Surgery and/or Interventional Treatment (SELECT)

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ClinicalTrials.gov Identifier: NCT03689244
Recruitment Status : Recruiting
First Posted : September 28, 2018
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE September 27, 2018
First Posted Date  ICMJE September 28, 2018
Last Update Posted Date November 25, 2020
Actual Study Start Date  ICMJE January 23, 2019
Estimated Primary Completion Date March 26, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
Percent of baseline Pulmonary vascular resistance (PVR) at Week 20 [ Time Frame: Week 20, within 2-5 hours post-dose ]
PVR is measured by right heart catheterization at rest and expressed as a percent of baseline PVR
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2020)
  • Change from baseline to Week 26 in 6-minute walk distance (6MWD) [ Time Frame: Week 26 ]
    The 6MWD test is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. The distance walked in 6 minutes is measured in meters at baseline (before double-blind study treatment initiation) and Week 26 (within 2-5 hours post-dose). Absolute change from baseline to Week 26 in 6MWD is expressed in meters.
  • Time to clinical worsening [ Time Frame: From baseline up to end of DB treatment visit (maximum 59 months) ]
    Time to clinical worsening is defined as at least one of the following components confirmed by the clinical event committee (CEC), when applicable: all-cause death, non-planned PH-related hospitalization, PH-related deterioration identified by increase from baseline in World Health Organization Functional Class (WHO FC) or deterioration from baseline in exercise capacity by at least 15 % or new or worsening signs/symptoms of right heart failure. Time from randomization to the first clinical worsening event up to end of DB treatment visit will be analyzed with the Kaplan-Meier survival estimates for each treatment arm.
  • All-Cause Death or Hospitalizations Related to PH Worsening [ Time Frame: Up to end of DB treatment visit (maximum 59 months) ]
    All-cause death or hospitalizations related to PH worsening will be assessed.
  • World Health Organization Functional Class (WHO FC) improvement at Week 26 [ Time Frame: Week 26 ]
    The following WHO FC classes are defined: Class I: no limitation of usual physical activity (PA); Class II: mild limitation of PA; Class III: marked limitation of PA; Class IV: unable to perform any PA without symptoms, Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. Changes to a lower WHO FC class (for instance from Class III to Class II) corresponds to a WHO FC improvement.
  • Change from baseline to Week 26 in Pulmonary arterial hypertension-symptoms and impact questionnaire (PAH-SYMPACT) Cardiopulmonary and Cardiovascular Symptom Domains [ Time Frame: Week 26 ]
    The PAH-SYMPACT questionnaire (including cardiopulmonary and cardiovascular symptoms domains). Absolute changes in symptom scores from baseline to week 26 will be calculated for each treatment arm.
  • Change from Baseline to Week 26 in Borg Dyspnea index or Borg CR10 Scale [ Time Frame: Week 26 ]
    Absolute changes in BDI/ borg category-ratio 10 (Borg CR10) scores from baseline to Week 26 will be calculated for each treatment arm. The Borg dyspnea index (BDI) or Borg CR10 scale rates the severity of dyspnea ((shortness of breath) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the BDI/Borg CR10 scores indicates an improvement. For each participant, BDI/Borg CR10 will be evaluated immediately after the exercise test (6MWD test).
  • Change from baseline to Week 26 in N-terminal pro b-type natriuretic peptide (NT pro-BNP) [ Time Frame: Week 26 ]
    Absolute changes in NT-pro BNP concentrations (pg/mL) from baseline to Week 26 will be calculated for each treatment arm.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
  • Change from baseline to Week 26 in 6-minute walk distance (6MWD) [ Time Frame: Week 26 ]
    The 6MWD test is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. The distance walked in 6 minutes is measured in meters at baseline (before double-blind study treatment initiation) and Week 26 (within 2-5 hours post-dose). Absolute change from baseline to Week 26 in 6MWD is expressed in meters.
  • Rate of pulmonary hypertension-related hospitalizations or death up to Week 52 [ Time Frame: From baseline to Week 52 ]
    This rate is calculated by dividing the total number of all-cause death or hospitalizations related to pulmonary hypertension (PH) worsening by the cumulative exposure of all subjects in each treatment arm.
  • Time to clinical worsening up to Week 52 [ Time Frame: From baseline to Week 52 ]
    Clinical worsening is a composite endpoint defined as any of the following events: all-cause death, non-planned PH-related hospitalization, PH-related deterioration identified by increased in World Health Organization Functional Class (WHO FC) or deterioration in exercise capacity by at least 15 % or signs/symptoms of right heart failure. Time from randomization to the first clinical worsening event up to Week 52 will be analyzed with the Kaplan-Meier survival estimates for each treatment arm.
  • Percentage of subjects with World Health Organization Functional Class (WHO FC) improvement at Week 26 [ Time Frame: Week 26 ]
    The following WHO FC classes are defined: Class I: no limitation of usual physical activity (PA); Class II: mild limitation of PA; Class III: marked limitation of PA; Class IV: unable to perform any PA without symptoms, Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. Changes to a lower WHO FC class (for instance from Class III to Class II) corresponds to a WHO FC improvement.
  • Change from baseline to Week 26 in PAH-SYMPACT™ scores [ Time Frame: Week 26 ]
    The PAH-SYMPACT™ questionnaire consists of two parts: the symptom part and the impact part. Absolute changes in symptom and impact scores from baseline to week 26 will be calculated for each treatment arm.
  • Change from baseline to Week 26 in Borg dypnea index [ Time Frame: Week 26 ]
    The Borg dyspnea index (BDI) rates the severity of dyspnea ((shortness of breath) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the BDI scores indicates an improvement. For each subject, BDI will be evaluated immediately after the exercise test (6MWD test). Absolute changes in BDI scores from baseline to Week 26 will be calculated for each treatment arm.
  • Change from baseline to Week 26 in N-terminal pro b-type natriuretic peptide (NT pro-BNP) [ Time Frame: Week 26 ]
    Absolute changes in NT-pro BNP concentrations (pg/mL) from baseline to Week 26 will be calculated for each treatment arm.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Find Out if Selexipag is Effective and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension When the Disease is Inoperable or Persistent/Recurrent After Surgery and/or Interventional Treatment
Official Title  ICMJE 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
Brief Summary Selexipag is available in many countries for the treatment of pulmonary arterial hypertension (PAH). Due to the similarities between PAH and chronic thromboembolic pulmonary hypertension (CTEPH) and the observed efficacy of other PAH medicines in CTEPH, it is believed that selexipag could benefit to patients with CTEPH. This study aims to assess the efficacy and safety of selexipag in subjects with inoperable or persistent/recurrent CTEPH.
Detailed Description Subjects will be recruited in two sequential cohorts: approximately the first 90 randomized subjects will undergo a right heart catheterization (RHC) (and left heart catheterization LHC, if needed) with measurement of pulmonary vascular resistance (PVR) at Week 20 and will constitute the hemodynamic cohort; the remaining participants will constitute the non-hemodynamic cohort; who do not require a post-baseline hemodynamic assessment. They will undergo the same overall study assessments as the hemodynamic cohort excepted for RHC at Week 20.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Thromboembolic Pulmonary Hypertension
Intervention  ICMJE
  • Drug: Selexipag
    oral tablets containing 200 µg of selexipag. Depending on the iMTD, subjects will receive 1 to 8 tablets at each administration
    Other Name: ACT-293987
  • Drug: Placebo
    Oral tablets without active compound
Study Arms  ICMJE
  • Experimental: Selexipag DB
    During the double blind treatment period, subjects in this group will receive selexipag. Each subject will start with one oral tablet of selexipag 200 µg in the evening of Day 1 and will continue with 200 µg twice daily (b.i.d.) on Day 2. If this dose is well-tolerated, selexipag is up-titrated with weekly increments of 200 µg until reaching the individual maximal tolerated dose (iMTD) in the range of 200 to 1600 µg b.i.d. The up-titration period up to Week 12 is followed by a stable maintenance treatment period from Week 12 to Week 26, at the iMTD. After Week 26, further up-titration can be allowed (but not above 1600 µg b.i.d.).
    Intervention: Drug: Selexipag
  • Placebo Comparator: Placebo DB
    During the double-blind treatment period, subjects in this group will receive the oral matching placebo, twice daily. A (mock) up-titration scheme will be followed.
    Intervention: Drug: Placebo
  • Experimental: Selexipag OL
    All subjects who completed the double-blind treatment period, whether they received placebo or selexipag during the double-blind period, will receive selexipag during the open-label extension period, using the same up-titration schedule as in the double-blind period.
    Intervention: Drug: Selexipag
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 12, 2020)
280
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2018)
400
Estimated Study Completion Date  ICMJE October 31, 2024
Estimated Primary Completion Date March 26, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Czechia,   Denmark,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03689244
Other Study ID Numbers  ICMJE AC-065B302
2018-002823-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Actelion is a Janssen pharmaceutical company of Johnson & Johnson. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu

URL: https://www.janssen.com/clinical-trials/transparency
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Cheryl Lassen, MD Actelion
PRS Account Actelion
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP