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

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ClinicalTrials.gov Identifier: NCT03942211
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE May 7, 2019
First Posted Date  ICMJE May 8, 2019
Last Update Posted Date April 14, 2021
Actual Study Start Date  ICMJE January 25, 2021
Estimated Primary Completion Date October 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2020)
Pulmonary Vascular Resistance (PVR) on Study Intervention up to Week 26 [ Time Frame: Up to week 26, within 2-5 hours post-dose ]
PVR is measured by right heart catheterization (RHC) and expressed as percent of baseline value.
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
Pulmonary vascular resistance (PVR) at peak concentration at Week 20 [ Time Frame: At week 20, within 2-5 hours post-dose ]
PVR is measured by right heart catheterization (RHC) and expressed as percent of baseline value.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
  • Time to clinical worsening (TTCW) up to Week 52 [ Time Frame: From baseline to Week 52 ]
    This is the time from randomization to the first clinical worsening event up to Week 52. Clinical worsening is defined as any of the following events: all-cause death, non-planned PH-related hospitalization, increase in World Health Organization Functional Class (WHO FC), deterioration in exercise capacity by at least 15 % from baseline as measured by the 6-minute walk distance or signs/symptoms of right heart failure.
  • Longitudinal trend of 6-minute walk distance (6MWD) up to Week 52 [ Time Frame: From baseline to week 52 ]
    The distance walked during the 6-minute walk test (6MWT) will be measured at different timepoints up to Week 52 for each participant.
  • Percentage of participants with oxygen desaturation post 6-minute walk test (6MWT) up to week 52 [ Time Frame: From baseine to Week 52 ]
    Oxygen desaturation is defined as a decrease in post-6MWT oxygen saturation (SpO2) by at least 5% from the respective pre-6MWT SpO2 value.
  • Percentage of participants with improvement, no change or worsening versus baseline in WHO FC up to Week 52 [ Time Frame: From baseline to Week 52 ]
    The following WHO FC classes are defined: Class I: no limitation of usual physical activity (PA); Class II: mild limitation of PA; Class III: marked limitation of PA; Class IV: unable to perform any PA without symptoms, Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. Change to a lower WHO FC class (for instance from Class III to Class II) corresponds to a WHO FC improvement. Change to a higher WHO FC class (for instance from Class II to Class III) corresponds to a WHO FC worsening.
  • Percentage of participants with all-cause death or PH-related hospitalization up to Week 52 [ Time Frame: From baseline to Week 52 ]
    Participants who have experienced at least one unplanned hospitalization related to PH or died from any cause up to Week 52 are reported.
  • Rate of all-cause death or PH-related hospitalizations up to Week 52 [ Time Frame: From baseline to week 52 ]
    This rate will be expressed as per 100-participant years, calculated by dividing the total number of all-cause death or hospitalizations related to PH-worsening by the cumulative exposure up to Week 52 of all participants in each intervention group.
  • Change from baseline up to Week 52 in SF-12 scores [ Time Frame: From baseline to Week 52 ]
    The SF-12 is a quality of life self-assessment questionnaire including items related to physical and mental/emotional health. Physical and mental scores are summarized.
  • Change from baseline up to Week 52 in King's sarcoidosis questionnaire (KSQ) scores [ Time Frame: From baseline to Week 52 ]
    KSQ is a health status questionnaire validated for patients with sarcoidosis. An overall KSQ score is summarized.
  • Change from baseline up to Week 39 in PAH-SYMPACT scores [ Time Frame: From baseline to Week 39 ]
    PAH-SYMPACT (Pulmonary Arterial Hypertension-Symptoms and Impact) is a self-rating questionnaire developed by Actelion and validated for patients with PAH to assess PAH-specific symptoms and their physical and cognitive/emotional impact. The symptom scores and the impact scores are summarized.
  • Change from baseline up to Week 52 in PGA-S scores [ Time Frame: From baseline to week 52 ]
    PGA (Patient Global Assessment of Severity) is a self-rating scale used to rate the overall severity of the disease with responses from "none" to "very severe".
  • Change from baseline up to Week 52 in CGI-S scores [ Time Frame: from baseline to Week 52 ]
    CGI-S (Clinical Global Impression of Severity) is a Clinician-reported outcome (CRO) used by the investigator to rate the severity of the participant's disease on the day of the CRO administration, with responses from "none" to "severe".
  • Change from baseline up to Week 52 in CGI-C scores [ Time Frame: from baseline to Week 52 ]
    CGI-C (Clinical Global Impression of Change) is a Clinician-reported outcome (CRO) used by the investigator to rate the change in the participant's disease on the day of the CRO administration compared to baseline (from "very much better" to "very much worse").
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study in Participants With Sarcoidosis-associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag
Official Title  ICMJE 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Sarcoidosis-associated Pulmonary Hypertension
Intervention  ICMJE
  • Drug: Selexipag
    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
    Other Name: JNJ-678896049; ACT-293987
  • Drug: Placebo
    Oral tablets without active compound. Participants can receive 1 to 8 tablets at each administration.
Study Arms  ICMJE
  • Experimental: Selexipag 200 micro gram (μg)
    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) bid/qd. Dosing frequency will be bid, except for participants with moderate hepatic impairment (Child-Pugh B) or who are concomitantly taking (a) moderate CYP2C8 inhibitor(s), who receive study intervention qd. The dose will be up-titrated by the investigator/delegate in 200 μg bid/qd 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 bid/qd.
    Intervention: Drug: Selexipag
  • Placebo Comparator: Placebo
    The comparator will be administered similarly to the experimental intervention.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 4, 2020)
74
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2019)
150
Estimated Study Completion Date  ICMJE March 15, 2024
Estimated Primary Completion Date October 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  • Confirmed diagnosis of sarcoidosis as per 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
  • 6MWD between 50 and 450 m both at Screening and at the time of randomization.
  • Forced vital capacity (FVC) >50% of predicted at Screening.
  • FEV1/FVC ≥60%, or if FEV1/FVC <60% then FEV1 must be ≥60% of predicted at Screening.
  • 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 agree to remain on an acceptable method while receiving study intervention and until 30 days after last dose of study intervention.
  • A woman using oral contraceptives must have been using this method for at least 1 month 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.
  • Received an investigational intervention or used an invasive investigational medical device within 90 days prior to randomization.
  • 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 (eg, use of walking aids (cane, walker, etc.), or lung function tests.
  • Any other criteria as per selexipag Summary of Product Characteristics (SmPC)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Belgium,   Brazil,   Canada,   France,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries Czechia
 
Administrative Information
NCT Number  ICMJE NCT03942211
Other Study ID Numbers  ICMJE AC-065D301
2018-004887-74 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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

URL: https://www.janssen.com/clinical-trials/transparency
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Rainer Zimmermann Actelion
PRS Account Actelion
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP