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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 (SELECT)

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ClinicalTrials.gov Identifier: NCT03689244
Recruitment Status : Recruiting
First Posted : September 28, 2018
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
Actelion

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.

Condition or disease Intervention/treatment Phase
Chronic Thromboembolic Pulmonary Hypertension Drug: Selexipag Drug: Placebo Phase 3

Detailed Description:
Subjects will be recruited in two sequential cohorts: the first 90 randomized subjects will undergo a right heart catheterization (RHC) 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; they will undergo the same overall study assessments as the hemodynamic cohort excepted for RHC at Week 20.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This study implements an adaptive group-sequential design with early futility or efficacy stopping rules and sample size re-estimation. An interim analysis (IA) will be carried out when approximately 90 subjects in the hemodynamic cohort have completed the assessments of PVR at Week 20 and 6-minute walk distance (6MWD) at Week 26. After the IA and sample size re-estimation for 6MWD, the number of subjects could be increased or decreased to between 150 and 400 based on conditional power considerations on 6MWD, if the study is not stopped early.

During the double-blind treatment period, subjects are randomized in a 1:1 ratio to receive either selexipag or placebo. During the open-label extension period, all the subjects will receive selexipag.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The first period of the study is conducted double blind (first 52 weeks). Then, subjects who complete the 52 weeks of the double-blind period will enter an open-label treatment extension period (up to 2 years)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : November 1, 2019
Estimated Study Completion Date : April 1, 2022


Arm Intervention/treatment
Experimental: Selexipag DB
During the double blind treatment period, subjects in this group will receive selexipag for 52 weeks. 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.).
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

Placebo Comparator: Placebo DB
During the double-blind treatment period, subjects in this group will receive the oral matching placebo for 52 weeks, twice daily. A (mock) up-titration scheme will be followed.
Drug: Placebo
Oral tablets without active compound

Experimental: Selexipag OL
All subjects who completed the 52 weeks of 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.
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Signed and dated informed consent form
  • Male and female subjects from 18 to 85 years old (inclusive).
  • 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 randomization.
  • Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e., selexipag) within 90 days prior to randomization.
  • Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC.
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03689244


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Argentina
Sanatorio de la Trinidad Mitre Recruiting
Buenos Aires, Argentina, C1039AAO
Belgium
UZ Leuven Recruiting
Leuven, Belgium, 3000
Hungary
Pécsi Tudományegyetem Klinikai Központ Recruiting
Pécs, Hungary, 7624
Israel
Rabin Medical Center, Beilinson Campus Recruiting
Petah Tikva, Israel, 4941492
The Chaim Sheba Medical Center Recruiting
Tel-Hashomer, Israel, 5265601
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Netherlands
VUMC Amsterdam Recruiting
Amsterdam, Netherlands, 1081 HV
Sweden
Norrlands Universitetssjukhus Recruiting
Umea, Sweden, 901 85
Turkey
Hacettepe University Medical Faculty Recruiting
Ankara, Turkey, 06100
Ankara University Medical Faculty Recruiting
Ankara, Turkey, 06500
Istanbul University Istanbul Medical Faculty Recruiting
Istanbul, Turkey, 34093
Istanbul University Cerrahpasa Medical Faculty Recruiting
Istanbul, Turkey, 34096
Marmara University Medical Faculty Recruiting
Istanbul, Turkey, 34899
Sponsors and Collaborators
Actelion
Investigators
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Study Director: Ralph Preiss, MD Actelion

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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT03689244     History of Changes
Other Study ID Numbers: AC-065B302
2018-002823-41 ( EudraCT Number )
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Actelion:
CTEPH
selexipag

Additional relevant MeSH terms:
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Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Selexipag
Antihypertensive Agents