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Sarcoidosis-associated Pulmonary HypertensionPhase 2SPHINXNCT03942211

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

A Phase 2 study testing Selexipag in people with Sarcoidosis-associated Pulmonary Hypertension, run by Actelion at 38 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Selexipag
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10 participants
Where
38 sitesin 10 countries
Study dates
26 Feb 2021to 19 Apr 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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)

Trial locations and contacts

38 sites in 10 countries.

38 sites in 10 countries

United States8 sites
  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

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

    Charleston, South Carolina, 29425-8900

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Cleveland Clinic

    Cleveland, Ohio, 44195-0001

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • St. Vincent Medical Group, Inc.

    Indianapolis, Indiana, 46260

  • LSU Health Sciences Center New Orleans

    New Orleans, Louisiana, 70112

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

Germany8 sites
  • Evangelische Lungenklinik Berlin

    Berlin, 13125

  • Universitatsklinikum Bonn

    Bonn, 53105

  • Universitatsklinikum Carl Gustav Carcus Dresden

    Dresden, 01307

  • Thoraxklinik Heidelberg

    Heidelberg, 69126

  • Universitatsklinikum Schleswig Holstein

    Lübeck, 23538

  • Universitaetsklinikum Regensburg

    Regensburg, 93053

  • RBK Lungenzentrum Stuttgart am Robert-Bosch-Krankenhaus

    Stuttgart, 70839

  • Klinikum Würzburg Mitte gGmbH Standort Missioklinik

    Würzburg, 97074

Other trials in Germany

France5 sites
  • Hôpital Avicenne

    Bobigny, 93000

  • GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel

    Bron, 69677

  • Hôpital Kremlin Bicêtre

    Le Kremlin-Bicêtre, 94270

  • Hopital Nord

    Marseille, 13915

  • CHU de Nancy - Hopital de Brabois

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Italy5 sites
  • Ospedale S.Giuseppe, Gruppo MultiMedica

    Milan, 20123

  • Fondazione Maugeri Montescano

    Pavia, 27100

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

    Roma, 00165

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

    Roma, 00168

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

    Torino, 10126

Other trials in Italy

Brazil3 sites
  • Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes

    Fortaleza, 60840-285

  • Hospital das Clinicas de Porto Alegre

    Porto Alegre, 90035-903

  • Hospital Das Clinicas Da Faculdade De Medicina Da USP

    São Paulo, 05403-000

Other trials in Brazil

Canada2 sites
  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

Other trials in Canada

Netherlands2 sites
  • VUMC Amsterdam

    Amsterdam, 1081 HV

  • Sint Antonius Ziekenhuis

    Nieuwegein, 3435 CM

Other trials in Netherlands

Spain2 sites
  • Hosp. Clinic de Barcelona

    Barcelona, 08036

  • Hosp. Univ. Marques de Valdecilla

    Santander, 39008

Other trials in Spain

United Kingdom2 sites
  • Royal Free Hospital

    London, NW3 2QG

  • Royal Brompton Hospital

    London, SW3 6NP

Other trials in United Kingdom

Belgium1 site
  • Universitaire Ziekenhuizen Leuven

    Leuven, 3000

Other trials in Belgium

About this study

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.

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).

Read the 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.

Being tested
Selexipag, Placebo
Keywords
selexipag, sarcoidosis, pulmonary hypertension
Medical subject headings
Sarcoidosis, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelexipagDrug

    Also called JNJ-678896049; ACT-293987

    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

  • PlaceboDrug

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

Study groups in NCT03942211
Study groupRoleWhat they receive
Selexipag 200 micro gram (μg)ExperimentalStudy 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.
Receives: Drug: Selexipag
PlaceboPlacebo comparatorThe comparator will be administered similarly to the experimental intervention.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline up to Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2019
  2. Study start26 Feb 2021
  3. Primary completion19 Apr 2023
  4. Study completion19 Apr 2023

Why it stopped: The sponsor decided to prematurely terminate the study due to the lower-than-expected recruitment rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03942211
Sponsor's protocol ID
AC-065D301
Other IDs
2018-004887-74, 2018
Acronym
SPHINX
Status last verified
Apr 2024
First submitted
7 May 2019
Last updated
8 May 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selexipag in people with Sarcoidosis-associated Pulmonary Hypertension, run by Actelion at 38 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Germany, France, Italy, Brazil and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pulmonary Vascular Resistance (PVR) up to Week 26 (time frame: Baseline up to Week 26). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.

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