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

  • Interventional
  • Recruiting
  • NCT03626688
Eligibility Details Visit Clinicaltrials.gov

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH

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.

Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable. The primary endpoint is the time (in days) from randomization to the first adjudicated protocol-defined clinical worsening event. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC) in a blinded fashion. Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on treatment 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.

Gender
All

Age Group
18 Years to 75 Years

Accepting Healthy Volunteers?
No

Inclusion Criteria:

         1. At least 18 years of age.

         2. Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.

         3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

         4. Primary diagnosis of symptomatic PAH

         5. Has had a right heart catheterization (RHC) performed at or within 3 years of Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH

         6. Has WHO/ NYHA functional class II to IV symptoms.

         7. If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatment.

         8. Has a 6MWD of ≥150 meters.

        Exclusion Criteria:

         1. For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Baseline.

         2. Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.

         3. Has evidence of more than mild lung disease on PFTs performed within 180 days prior to, or during Screening.

         4. Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.

         5. Current diagnosis of uncontrolled sleep apnea as defined by the Investigator.

         6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG measured at Screening or Baseline in subjects without evidence of intraventricular conduction delay (IVCD). In the presence of IVCD, subjects will be excluded if the QTcF >500 msec for both males and females.

         7. Severe chronic liver disease (ie, Child-Pugh C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).

         8. Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

         9. Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.

         10. Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.

         11. Hemoglobin concentration <9 g/dL at Screening.

         12. Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) at any time prior to Baseline (use in vasoreactive testing is permitted).

         13. Subjects treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) that was stopped for a safety or tolerability issue.

         14. Subject has pulmonary veno-occlusive disease.

         15. Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.

         16. Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse.

At a Glance

National Government IDNCT03626688

IRB#IRB18-1203

Lead SponsorUnited Therapeutics

Lead PhysicianRemzi Bag

Collaborator(s)N/A

EligibilityAll
18 Years to 75 Years
Recruiting