Clinical trial NCT03942211: A Study in Participants With Sarcoidosis-associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Sarcoidosis-Associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sarcoidosis-associated Pulmonary Hypertension
Keywords: selexipag, sarcoidosis, pulmonary hypertension
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2019-05-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Oral selexipag is commercially available in several countries for the treatment of a particular group of pulmonary hypertension (PH) called pulmonary arterial hypertension (PAH). The aim of the present study is to investigate whether selexipag could be helpful to treat patients with another form of PH called sarcoidosis-associated pulmonary hypertension (SAPH).

Detailed description: Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and can complicate several cardiovascular and respiratory diseases. Sarcoidosis is a multisystemic disorder that is characterized by non-caseating granulomas which are present in multiple tissues, particularly in the lung and lymphatic system. Severe untreated pulmonary hypertension (PH) carries a poor prognosis and is associated with higher mortality in participants with interstitial lung diseases and sarcoidosis. While there is no approved treatment for SAPH, PH-specific treatments are frequently used. Selexipag is a selective, orally available and long-acting non-prostanoid agonist of the prostacyclin receptor (prostacyclin \[IP\] receptor) for the treatment of patients with PAH. The rationale for this study is based on the unmet medical need for new therapeutic options for patients with SAPH and is supported by the established efficacy and safety of selexipag in the PAH indication, the shared pathomechanism between SAPH and PAH, and the available data on the efficacy and safety of PH-specific therapies in SAPH. This study consists of screening period, main observation period and double blind extension period and safety follow-up period. The duration of individual participation in the study will be different for each individual participant (between approximately 15 months and up to approximately 3.5 years) and will depend on the time of each participant's individual date of entering the study and the total recruitment time. The efficacy assessments include right heart catheterization (RHC), assessment of exercise capacity, dyspnea, pulmonary function tests, etc. Safety and tolerability will be evaluated throughout the study and includes review of concomitant medications and adverse events (AEs), clinical laboratory tests, 12-lead electrocardiogram (ECG), vital signs, physical examination, and pregnancy testing.

Eligibility criteria: Main Inclusion Criteria:

* Confirmed diagnosis of sarcoidosis as per American Thoracic Society (ATS) criteria
* Sarcoidosis-associated precapillary PH, confirmed by RHC (at rest) within 90 days prior to randomization.
* PH severity according to modified WHO FC II-IV at Screening and randomization; participants in WHO FC IV must be in a stable condition and able to perform a 6MWT.
* Either not receiving treatment with PH-specific treatment or oral PH-specific monotherapy (ie, riociguat or PDE5i or ERA); if on oral PH-specific monotherapy then treatment had to be stable (ie, no introduction of new therapies or changes in dose) for at least 90 days prior to both and the RHC qualifying for enrollment and randomization
* Stable sarcoidosis treatment regimen, ie, no new specific anti-inflammatory treatment for sarcoidosis for at least 90 days, and stable dose(s) for at least 30 days prior to both the RHC qualifying for enrollment and randomization
* 6-minute walk distance (6MWD) greater than or equal to (\>=) 50 meters both at Screening and at the time of randomization. Participants can use their usual walking aids during the test (example, cane, crutches). The same walking aid should be used for all 6-minute walk test (6MWTs). Walkers are not allowed
* Forced Vital Capacity (FVC) greater than (\>) 50 percent (%) and Forced Expiratory Volume (in 1 second) (FEV1) \> 50% of predicted at Screening
* Diffusing capacity of the lung for carbon monoxide (DLCO) \>= 40% of predicted. If DLCO less than (\<) 40% of predicted, the extent of emphysema should not be greater than that of fibrosis as assessed by high resolution computerized tomography (CT) scan
* Women of childbearing potential must have a negative pregnancy test at screening and randomization, must agree to undertake monthly urine pregnancy tests, and to practice an acceptable method of contraception and agreeing to remain on an acceptable method while receiving study intervention and until 30 days after last dose of study intervention
* A woman only using hormonal contraceptives must have been using this method for at least 30 days prior to randomization

Main Exclusion Criteria:

* PH due to left heart disease (PAWP \>15 mmHg).
* History of left heart failure (LHF) as assessed by the investigator including cardiomyopathies, and cardiac sarcoidosis, with a left ventricular ejection fraction (LVEF) \<40%.
* Treatment with prostacyclin, prostacyclin analogues or IP receptor agonists (ie, selexipag) within 90 days prior to randomization and/or prior to the RHC qualifying for enrollment, except those given at vasodilator testing during RHC.
* SBP \<90 mmHg at Screening or at randomization.
* Included on a lung transplant list or planned to be included until Visit 6 / Week 39.
* Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to RHC qualifying for enrollment.
* Any condition for which, in the opinion of the investigator, participation would not be in the best interests of the participant (eg, compromise well-being), or that could prevent, limit, or confound the protocol-specified assessments.
* Any acute or chronic impairment that may influence the ability to comply with study requirements such as to perform RHC, a reliable and reproducible 6MWT, or lung function tests.
* Any other criteria as per selexipag Summary of Product Characteristics (SmPC)

Primary outcomes:
measure: Pulmonary Vascular Resistance (PVR) up to Week 26
timeFrame: Baseline up to Week 26
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: St. Vincent Medical Group, Inc.
state: Indiana
city: New Orleans
country: United States
facility: LSU Health Sciences Center New Orleans
state: Louisiana
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) - College of Medicine (COM)
state: South Carolina
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Fortaleza
country: Brazil
facility: Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Sao Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bron Cedex
country: France
facility: GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel
city: Le Kremlin Bicetre Cedex
country: France
facility: Hôpital Kremlin Bicêtre
city: Marseille cedex 20
country: France
facility: Hopital Nord
city: Vandoeuvre les Nancy Cedex
country: France
facility: CHU de Nancy - Hopital de Brabois
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carcus Dresden
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Luebeck
country: Germany
facility: Universitatsklinikum Schleswig Holstein
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Stuttgart
country: Germany
facility: RBK Lungenzentrum Stuttgart am Robert-Bosch-Krankenhaus
city: Würzburg
country: Germany
facility: Klinikum Würzburg Mitte gGmbH Standort Missioklinik
city: Milano
country: Italy
facility: Ospedale S.Giuseppe, Gruppo MultiMedica
city: Pavia
country: Italy
facility: Fondazione Maugeri Montescano
city: Roma
country: Italy
facility: Umberto I Pol. di Roma-Università di Roma La Sapienza
city: Roma
country: Italy
facility: Universita Cattolica del Sacro Cuore - Fondazione Policlinico Universitario 'A. Gemelli'
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza
city: Amsterdam
country: Netherlands
facility: VUMC Amsterdam
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Barcelona
country: Spain
facility: Hosp. Clinic de Barcelona
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Actelion
name: Rainer Zimmermann
role: STUDY_DIRECTOR
References: