A Study in Participants With Sarcoidosis-associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag

NCT03942211 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: AC-065D3012018-004887-74
• Study Type: interventional
• Target: 10
• Locations: 10 countries
• Sites: 38

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).

Conditions

Sarcoidosis-associated Pulmonary Hypertension

Keywords

selexipag, sarcoidosis, pulmonary hypertension

Outcome Measures

Primary Outcomes (1)

• Pulmonary Vascular Resistance (PVR) up to Week 26

  PVR represents the resistance against which the right ventricle needs to pump. PVR was determined by right heart catheterization (RHC). It was measured as the ratio of the PVR value post-treatment initiation up to Week 26 (post) versus the PVR value pre-treatment initiation at baseline (pre), expressed as a percentage of baseline value. The baseline reference value for PVR was based on the last RHC performed prior to study intervention initiation. PVR was calculated as 80\*(mean pulmonary arterial pressure - pulmonary artery wedge pressure) divided by cardiac output. As specified in the statistical analysis plan, data was not planned to be summarized for this outcome measure and only individual participant wise data was collected.

  Baseline up to Week 26

Study Arms (2)

Selexipag 200 micro gram (μg)

EXPERIMENTAL

Study intervention will be up-titrated to allow each participant to reach their individual maximum tolerated dose (iMTD), in the range of 200 μg to1600 μg (ie, 1 to 8 tablets) twice daily/once daily. Dosing frequency will be twice daily, except for participants with moderate hepatic impairment (Child-Pugh Class B) or who are concomitantly taking (a) moderate CYP2C8 inhibitor(s), who receive study intervention once daily. The dose will be up-titrated by the investigator/delegate in 200 μg twice daily/once daily increments at weekly intervals during scheduled TCs until reaching the iMTD. If the dose regimen is not well tolerated or symptoms cannot be fully managed with symptomatic treatment, the duration of the titration step can be prolonged to 2 weeks. If needed, the dose can be reduced by 200 μg twice daily/once daily.

Drug: Selexipag

Placebo

PLACEBO COMPARATOR

The comparator will be administered similarly to the experimental intervention.

Drug: Placebo

Interventions

Selexipag DRUG

Oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 (200 µg) to 8 (1600 µg) tablets at each administration

Also known as: JNJ-678896049; ACT-293987

Selexipag 200 micro gram (μg)

Placebo DRUG

Oral tablets without active compound. Participants can receive 1 to 8 tablets at each administration.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Actelion: lead

Study Sites (38)

St. Vincent Medical Group, Inc.

Indianapolis, Indiana, 46260, United States

Location

LSU Health Sciences Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195-0001, United States

Location

Medical University of South Carolina (MUSC) - College of Medicine (COM)

Charleston, South Carolina, 29425-8900, United States

Location

Universitaire Ziekenhuizen Leuven

Leuven, 3000, Belgium

Location

Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes

Fortaleza, 60840-285, Brazil

Location

Hospital das Clinicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, 05403-000, Brazil

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel

Bron, 69677, France

Location

Hôpital Kremlin Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Hopital Nord

Marseille, 13915, France

Location

CHU de Nancy - Hopital de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Universitatsklinikum Bonn

Bonn, 53105, Germany

Location

Universitatsklinikum Carl Gustav Carcus Dresden

Dresden, 01307, Germany

Location

Thoraxklinik Heidelberg

Heidelberg, 69126, Germany

Location

Universitatsklinikum Schleswig Holstein

Lübeck, 23538, Germany

Location

Universitaetsklinikum Regensburg

Regensburg, 93053, Germany

Location

RBK Lungenzentrum Stuttgart am Robert-Bosch-Krankenhaus

Stuttgart, 70839, Germany

Location

Klinikum Würzburg Mitte gGmbH Standort Missioklinik

Würzburg, 97074, Germany

Location

Ospedale S.Giuseppe, Gruppo MultiMedica

Milan, 20123, Italy

Location

Fondazione Maugeri Montescano

Pavia, 27100, Italy

Location

Umberto I Pol. di Roma-Università di Roma La Sapienza

Roma, 00165, Italy

Location

Universita Cattolica del Sacro Cuore - Fondazione Policlinico Universitario 'A. Gemelli'

Roma, 00168, Italy

Location

A.O.U. Città della Salute e della Scienza

Torino, 10126, Italy

Location

VUMC Amsterdam

Amsterdam, 1081 HV, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, 3435 CM, Netherlands

Location

Hosp. Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

MeSH Terms

Conditions

Sarcoidosis; Hypertension, Pulmonary

Interventions

selexipag

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

All planned efficacy analyses could not be performed due to early termination of study.

Results Point of Contact

• Title: Global Medical Head
• Organization: Janssen Cilag International NV

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Rainer Zimmermann

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 8, 2019
• Study Start: February 26, 2021
• Primary Completion: April 19, 2023
• Study Completion: April 19, 2023
• Last Updated: May 8, 2024
• Results First Posted: May 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8); CA (2); FR (5); ES (2); DE (8); GB (2); IT (5); BE (1); BR (3); NL (2)