Trial Outcomes & Findings for A Study in Participants With Sarcoidosis-associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag (NCT NCT03942211)

Last Updated: 2024-05-08

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline up to Week 26

Results posted on

2024-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	Selexipag 200 Micrograms (mcg) Participants received a single oral tablet of selexipag 200 mcg on Day 1. The dose was up-titrated by the investigator/delegate at weekly intervals to allow each participant to reach their individual maximum tolerated dose (iMTD), in the range of 200 mcg to 1600 mcg (that is, 1 to 8 tablets) twice daily from Day 2 to Week 12 or until reaching iMTD. From Week 12 onwards, participants received their iMTD of selexipag orally twice daily till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.	Placebo Participants received placebo matching to selexipag 1 to 8 tablets twice daily from Day 1 till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.
Overall Study STARTED	6	4
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Selexipag 200 Micrograms (mcg) Participants received a single oral tablet of selexipag 200 mcg on Day 1. The dose was up-titrated by the investigator/delegate at weekly intervals to allow each participant to reach their individual maximum tolerated dose (iMTD), in the range of 200 mcg to 1600 mcg (that is, 1 to 8 tablets) twice daily from Day 2 to Week 12 or until reaching iMTD. From Week 12 onwards, participants received their iMTD of selexipag orally twice daily till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.	Placebo Participants received placebo matching to selexipag 1 to 8 tablets twice daily from Day 1 till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.
Overall Study Death	1	0
Overall Study Study terminated by sponsor	5	3
Overall Study Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selexipag 200 Micrograms (mcg) n=6 Participants Participants received a single oral tablet of selexipag 200 mcg on Day 1. The dose was up-titrated by the investigator/delegate at weekly intervals to allow each participant to reach their individual maximum tolerated dose (iMTD), in the range of 200 mcg to 1600 mcg (that is, 1 to 8 tablets) twice daily from Day 2 to Week 12 or until reaching iMTD. From Week 12 onwards, participants received their iMTD of selexipag orally twice daily till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.	Placebo n=4 Participants Participants received placebo matching to selexipag 1 to 8 tablets twice daily from Day 1 till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	55 years STANDARD_DEVIATION 14.53 • n=5 Participants	68.5 years STANDARD_DEVIATION 2.38 • n=7 Participants	60.4 years STANDARD_DEVIATION 12.95 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment France	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Germany	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United Kingdom	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 26

Population: Randomized analysis set included all participants assigned to the study intervention. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants randomized and analyzed in respective treatment arm. Here, 'n' (number analyzed)=0 signifies that the participant was not randomized in that treatment arm.

Outcome measures

Outcome measures
Measure	Selexipag 200 Micrograms (mcg) n=5 Participants Participants received a single oral tablet of selexipag 200 mcg on Day 1. The dose was up-titrated by the investigator/delegate at weekly intervals to allow each participant to reach their individual maximum tolerated dose (iMTD), in the range of 200 mcg to 1600 mcg (that is, 1 to 8 tablets) twice daily from Day 2 to Week 12 or until reaching iMTD. From Week 12 onwards, participants received their iMTD of selexipag orally twice daily till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.	Placebo n=3 Participants Participants received placebo matching to selexipag 1 to 8 tablets twice daily from Day 1 till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 2	—	201 percentage of baseline PVR
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 3	—	56 percentage of baseline PVR
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 4	88 percentage of baseline PVR	—
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 5	100 percentage of baseline PVR	—
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 6	47.0 percentage of baseline PVR	—
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 7	82.0 percentage of baseline PVR	—
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 8	86.0 percentage of baseline PVR	—
Pulmonary Vascular Resistance (PVR) up to Week 26 Participant 1	—	89.0 percentage of baseline PVR

Adverse Events

Selexipag 200 Micrograms (mcg)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Placebo

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Selexipag 200 Micrograms (mcg) n=6 participants at risk Participants received a single oral tablet of selexipag 200 mcg on Day 1. The dose was up-titrated by the investigator/delegate at weekly intervals to allow each participant to reach their individual maximum tolerated dose (iMTD), in the range of 200 mcg to 1600 mcg (that is, 1 to 8 tablets) twice daily from Day 2 to Week 12 or until reaching iMTD. From Week 12 onwards, participants received their iMTD of selexipag orally twice daily till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.	Placebo n=4 participants at risk Participants received placebo matching to selexipag 1 to 8 tablets twice daily from Day 1 till end of treatment (up to 456 days). For participants with moderate hepatic impairment (Child-Pugh Class B) or who were concomitantly taking moderate CYP2C8 inhibitor(s) the dosing frequency was once daily.
Cardiac disorders Angina Pectoris	0.00% 0/6 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	25.0% 1/4 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Cardiac disorders Cardiac Failure	16.7% 1/6 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	0.00% 0/4 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Infections and infestations Pneumonia	16.7% 1/6 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	0.00% 0/4 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Infections and infestations Pneumonia Aspiration	0.00% 0/6 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	25.0% 1/4 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Infections and infestations Urinary Tract Infection	16.7% 1/6 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	0.00% 0/4 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Injury, poisoning and procedural complications Fall	16.7% 1/6 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	0.00% 0/4 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	25.0% 1/4 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.00% 0/6 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.	25.0% 1/4 • Number of events 1 • From Day 1 up to 456 days Safety assessments were based on the safety analysis set which included all participants who received at least one dose of study intervention.

Other adverse events

Additional Information

Global Medical Head

Janssen Cilag International NV

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER