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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03689244




Registration number
NCT03689244
Ethics application status
Date submitted
27/09/2018
Date registered
28/09/2018
Date last updated
9/06/2020

Titles & IDs
Public title
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 International Treatment
Scientific 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
Secondary ID [1] 0 0
2018-002823-41
Secondary ID [2] 0 0
AC-065B302
Universal Trial Number (UTN)
Trial acronym
SELECT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Thromboembolic Pulmonary Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Selexipag
Treatment: Drugs - Placebo

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.).

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.

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.


Treatment: Drugs: Selexipag
oral tablets containing 200 µg of selexipag. Depending on the iMTD, subjects will receive 1 to 8 tablets at each administration

Treatment: Drugs: Placebo
Oral tablets without active compound

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent of baseline Pulmonary vascular resistance (PVR) at Week 20 - PVR is measured by right heart catheterization at rest and expressed as a percent of baseline PVR
Timepoint [1] 0 0
Week 20, within 2-5 hours post-dose
Secondary outcome [1] 0 0
Change from baseline to Week 26 in 6-minute walk distance (6MWD) - 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.
Timepoint [1] 0 0
Week 26
Secondary outcome [2] 0 0
Time to clinical worsening - 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 signs/symptoms of right heart failure. Time from randomization to the first clinical worsening eventup to end of DB treatment visit will be analyzed with the Kaplan-Meier survival estimates for each treatment arm.
Timepoint [2] 0 0
From baseline up to end of DB treatment visit (maximum 52 months)
Secondary outcome [3] 0 0
All-Cause Death or Hospitalizations Related to PH Worsening - All-cause death or hospitalizations related to PH worsening will be assessed.
Timepoint [3] 0 0
Up to end of DB treatment visit (maximum 52 months)
Secondary outcome [4] 0 0
Percentage of subjects with World Health Organization Functional Class (WHO FC) improvement at 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.
Timepoint [4] 0 0
Week 26
Secondary outcome [5] 0 0
Change from baseline to Week 26 in PAH-SYMPACT Cardiopulmonary and Cardiovascular Symptom Domains - The PAH-SYMPACT questionnaire (including cardiopulmonary and cardiovascular symptom domains). Absolute changes in symptom scores from baseline to week 26 will be calculated for each treatment arm.
Timepoint [5] 0 0
Week 26
Secondary outcome [6] 0 0
Change from Baseline to Week 26 in Borg Dyspnea index or Borg CR10 Scale - 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).
Timepoint [6] 0 0
Week 26
Secondary outcome [7] 0 0
Change from baseline to Week 26 in N-terminal pro b-type natriuretic peptide (NT pro-BNP) - Absolute changes in NT-pro BNP concentrations (pg/mL) from baseline to Week 26 will be calculated for each treatment arm.
Timepoint [7] 0 0
Week 26

Eligibility
Key inclusion criteria
Main

- 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
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Queensland Lung Transplant Service - Chermside
Recruitment hospital [3] 0 0
St Vincent's hospital - Darlinghurst
Recruitment hospital [4] 0 0
Pulmonary Arterial Hypertension Clinic - Hobart
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment outside Australia
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Washington
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Wisconsin
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Argentina
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Buenos Aires
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Caba
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Argentina
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Ciudad Autónoma de Buenos Aires
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Uppsala
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Taichung
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Khon Kaen
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Istanbul
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Izmir
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Kartal-Istanbul
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Ukraine
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Dnipro
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Ukraine
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Kyiv
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Lviv
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Cambridge
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Glasgow
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Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03689244
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ralph Preiss, MD
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03689244