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

Study Purpose

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 participants with inoperable or persistent/recurrent CTEPH.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 85 Years
Gender	All

More Inclusion & Exclusion Criteria

Main

Inclusion Criteria:

- Signed and dated informed consent form.

- Male and female participants 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.

- Participant 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03689244
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Actelion
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Julian Borissoff, MD, PhD
Principal Investigator Affiliation	Actelion
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Germany, Hungary, India, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Chronic Thromboembolic Pulmonary Hypertension

Additional Details

Participants will be recruited in two sequential cohorts: approximately the first 90 randomized participants 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.

Arms & Interventions

Arms

Experimental: Selexipag DB

During the double blind treatment period, participants in this group will receive selexipag. Each participant 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, participants in this group will receive the oral matching placebo, twice daily. A (mock) up-titration scheme will be followed.

Experimental: Selexipag OL

All participants 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.

Interventions

Drug: - Selexipag

oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration

Drug: - Placebo

Oral tablets without active compound

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mayo Clinic Arizona, Phoenix, Arizona

Status

Withdrawn

Address

Mayo Clinic Arizona

Phoenix, Arizona, 85054

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