Last updated on August 2019

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients


Brief description of study

Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.

Detailed Study Description

Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study that includes a Screening period of up to 28 days in duration, a 16-week (1123 days) Dose Titration Period, and a Treatment Period of variable duration, depending upon the overall duration of the trial. A total of 700 subjects with WHO Group 1 PAH are planned to be enrolled. Subjects who meet all entry criteria will be randomized 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable.

Randomization will be stratified by: Screening 6MWD <400 meters versus 400 meters, PAH associated with connective tissue disease (CTD) versus other etiologies, and PAH specific background therapy (2 versus 1 or none).

On Day 1, investigational medicinal product (IMP) (ralinepag or placebo) will be initiated at a dose of 50 mcg once daily for the first week of treatment. During each subsequent week of the 16 week Dose Titration Period, the dose of IMP will be increased in 50 mcg increments to a dose of 800 mcg once daily or until the highest tolerated dose is achieved.

Subjects will be required to attend clinic visits on Day 1 (Baseline) and at Weeks 4, 8, and 12 during the Dose Titration Period. Between scheduled clinic visits during the Dose Titration Period, subjects will be contacted at least once per week by telephone to titrate IMP dose (up or down), review IMP administration instructions, assess adverse events (AEs), and record concomitant medications. If the highest tolerated dose of IMP is achieved prior to Week 16, the subject will remain on that dose until the completion of the Dose Titration Period. Decreases in IMP dose (in 50 mcg increments) will be allowed at any time during the Dose Titration Period to manage AEs and attain the highest tolerated dose. Background PAH therapies (regimen and doses) must remain stable throughout the Dose Titration Period.

Further increases in IMP dose (in increments of 50 mcg per week) up to a maximum dose of 1450 mcg once daily will be permitted during the Treatment Period, according to investigator discretion. No IMP dose increases will be allowed within 6 weeks prior to a protocol-specified efficacy evaluation. IMP dose decreases will be allowed at any time during the Treatment Period to manage tolerability and AEs. IMP dose adjustments (up or down) may be implemented by phone or during an Unscheduled Visit between protocol-specified clinic visits.

Subjects will attend clinic visits at Week 16 and every 12 weeks (843 days) thereafter during the Treatment Period. Efficacy and safety assessments will be performed at every visit until a total of 253 primary endpoint events have occurred. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC). The CEC will remain blinded to treatment assignments throughout the duration of the study.

All subjects should remain on IMP for the duration of the trial. Subjects who prematurely discontinue IMP should continue in the study and complete remaining scheduled visits according to the protocol. Subjects who withdraw from the study (during the Dose Titration Period or the Treatment Period) and do not agree to complete their remaining scheduled visits will be requested to return to clinic for the End of Study/Early Termination Visit and for a Follow up Visit approximately 30 days after discontinuation of IMP. Subjects who prematurely discontinue IMP or withdraw from the study will also be contacted each year and at the end of the study to determine vital status (unless consent is withdrawn).

Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on IMP at the conclusion of the study (after the target number of events is achieved) will have the option to enroll in an open-label extension (OLE) study and receive treatment with ralinepag. Subjects who do not choose to participate in the OLE will discontinue IMP and may receive standard of care PAH treatment off-study, at the discretion of the treating physician. Subjects who do not participate in the OLE study will attend a Follow-up Visit approximately 30 days after discontinuation of IMP. Subjects who prematurely discontinue IMP or withdraw from Study ROR-PH-301 for any reason (other than experiencing a confirmed primary endpoint event) will not be eligible to continue into the OLE study.

Clinical Study Identifier: NCT03626688

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