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.
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
- Conditions the study is for
- Sarcoidosis-associated Pulmonary Hypertension
- 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
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
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
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
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
Canada2 sites
London Health Sciences Centre
London, Ontario, N6A 5W9
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Netherlands2 sites
VUMC Amsterdam
Amsterdam, 1081 HV
Sint Antonius Ziekenhuis
Nieuwegein, 3435 CM
Spain2 sites
Hosp. Clinic de Barcelona
Barcelona, 08036
Hosp. Univ. Marques de Valdecilla
Santander, 39008
United Kingdom2 sites
Royal Free Hospital
London, NW3 2QG
Royal Brompton Hospital
London, SW3 6NP
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Selexipag |
| Placebo | Placebo comparator | The 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.
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.
- First posted8 May 2019
- Study start26 Feb 2021
- Primary completion19 Apr 2023
- Study completion19 Apr 2023
Why it stopped: The sponsor decided to prematurely terminate the study due to the lower-than-expected recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sarcoidosis-associated Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rainer Zimmermann, Study director, Actelion
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03942211
- Acronym / sponsor ID
- SPHINX / AC-065D301
- Keywords
- selexipag, sarcoidosis, pulmonary hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to prematurely terminate the study due to the lower-than-expected recruitment rate
- Enrolment
- 10 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 26 Feb 2021 (actual)
- Primary completion
- 19 Apr 2023 (actual)
- Study completion
- 19 Apr 2023 (actual)
- First posted
- 8 May 2019 (actual)
- Results
- Posted 8 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Selexipag 200 micro gram (μg) | Experimental | Drug: SelexipagStudy 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. |
| Placebo | Placebo comparator | Drug: PlaceboThe comparator will be administered similarly to the experimental intervention. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelexipagAlso: JNJ-678896049; ACT-293987Oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 (200 µg) to 8 (1600 µg) tablets at each administration | Drug | Selexipag 200 micro gram (μg) |
| PlaceboOral tablets without active compound. Participants can receive 1 to 8 tablets at each administration. | Drug | Placebo |
Primary outcome
Pulmonary Vascular Resistance (PVR) up to Week 26
Time frame: Baseline 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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
Related trials for Sarcoidosis-associated Pulmonary Hypertension
Not yet recruitingPhase 2
LAM-001 for the Treatment of Sarcoidosis Associated Pulmonary Hypertension (SAPH)
Sarcoidosis Associated Pulmonary Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer Zimmermann study director
Actelion
38 sites in 10 countries: see every site and its status.
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.