A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH

Overview

Study ROR-PH-302, ADVANCE CAPACITY, is designed to evaluate the effects of ralinepag therapy on exercise capacity as assessed by change in peak oxygen consumption (VO2) derived from cardiopulmonary exercise testing (CPET) after 28 weeks of treatment

Full Title of Study: “A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Ralinepag to Evaluate Safety and Effects on Exercise Capacity Assessed by CPET in Subjects With WHO Group 1 Pulmonary Hypertension Who Recently Initiated Therapy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 15, 2022

Detailed Description

ROR-PH-302 is a 28-week multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 2:1 to receive ralinepag or placebo, in addition to their PAH-specific background therapy, as applicable. The primary endpoint is change from Baseline in peak VO2 (assessed by CPET) at Week 28. All subjects who complete the study on study drug through Week 28 will have the option to receive ralinepag in an open-label extension (OLE) study.

Interventions

  • Drug: Ralinepag
    • Oral ralinepag
  • Drug: Placebo
    • Matching oral tablets

Arms, Groups and Cohorts

  • Experimental: Ralinepag
    • Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose (maximum dose of 1400 mcg)
  • Placebo Comparator: Placebo
    • Matching placebo tablets (oral)

Clinical Trial Outcome Measures

Primary Measures

  • Change from Baseline in peak VO2 assessed by CPET
    • Time Frame: Baseline to Week 28
    • Peak VO2 by CPET was measured at Baseline (prior to starting study drug) and Week 28

Secondary Measures

  • Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
    • Time Frame: Baseline to Week 28
    • NT-proBNP was measured at Baseline (prior to starting study drug) and Weeks 4, 8, 12, 16, 20, 24 and 28
  • Change from Baseline in Minute Ventilation (VE)/Carbon Dioxide output (VCO2) slope
    • Time Frame: Baseline to Week 28
    • VE/VCO2 slope (from CPET) was calculated at Baseline (prior to starting study drug) and Week 28
  • Change from Baseline in Health-related quality of life (HRQoL) measured by the Short Form (36) Health Survey (SF-36) Scores
    • Time Frame: Baseline to Week 28
    • SF-36 was assessed at Baseline (prior to starting study drug) and Weeks 16 and 28
  • Time to First All-cause Non-elective Hospitalization
    • Time Frame: Baseline to Week 28
    • The time to first all-cause nonelective hospitalization during the study period will be assessed.

Participating in This Clinical Trial

Inclusion Criteria

1. At least 18 years of age

2. Primary diagnosis of PAH

3. Has had a diagnostic RHC performed within 1 year of Screening

4. Has World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) 2 to 3 symptoms

5. Must have initiated first PAH-specific oral therapy with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a sGC stimulator within 9 months prior to Screening

6. Has a 6-minute walk distance (6MWD) of ≥150 meters at Screening

7. Has a VE/VCO2 slope ≥38 during the Screening CPET, as assessed by the CPET core lab

8. Has a peak VO2 of ≥10 to <18 mL·kg-1·min-1 during the Screening CPET, as assessed by the CPET core lab

Exclusion Criteria

1. Has left ventricular disease

2. Current unstable angina

3. Symptomatic coronary disease and/or myocardial infarction within past 6 months

4. Current symptomatic aortic or mitral valve disease

5. Has evidence of more than mild lung disease on pulmonary function tests (PFTs) performed within 1 year prior to, or during, Screening

6. Has evidence of thromboembolic disease

7. Current diagnosis of uncontrolled sleep apnea in the opinion of the Investigator

8. Requires use of supplemental oxygen during CPET

9. Respiratory exchange ratio (RER) <1.0 at Screening CPET as determined by the CPET core laboratory

10. Acute non-cardiac disorder that may affect exercise performance or be aggravated by exercise (eg, infection, renal failure, thyrotoxicosis)

11. Male subjects with a QTcF >450 msec and female subjects with QTcF >470 msec on electrocardiogram (ECG)

12. 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • United Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • David Yehle, RPh, Study Director, United Therapeutics
  • Overall Contact(s)
    • Louis Holdstock, PhD, 919-425-8866, lholdstock@unither.com

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