CLINICAL TRIAL / NCT03626688
A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
- Interventional
- Recruiting
- NCT03626688
Contact Information
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 who have
completed the Week 28 Visit (after the target number of confirmed events is achieved)
will have the option to enroll in an open-label extension (OLE) study. Subjects who do
not choose to participate in the OLE study will discontinue study drug and should remain
in the study for long-term follow-up of survival status and will receive standard of care
PAH treatment, at the discretion of the treating physician.
Gender
All
Age Group
18 Years and up
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 prior to
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.
8. Has a 6MWD of ≥150 meters.
9. If taking concomitant medications that may affect the clinical manifestations of PAH
(eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation,
beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor
blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit
and the dosage maintained throughout the study. The exception is that the dose of
diuretics must be stable for at least the 10 days prior to Baseline.
10. Both male and female subjects agree to use a highly effective method of birth
control throughout the entire study period from informed consent through to the
30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and
female subjects must also agree not to participate in a conception process during
the study and for 30 days after the last dose of IMP. Eligible male subjects must
agree not to participate in sperm donation for 90 days after the last dose of IMP.
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 pulmonary function tests 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 ongoing and clinically significant 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 recorded at Screening and
analyzed by the central ECG laboratory. Subjects with evidence of intraventricular
conduction delay, defined as a QRS interval greater than 110 msec, will be excluded
if the QTcF is >500 msec for both males and females.
7. Severe chronic liver disease (ie, Child-Pugh Class 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 or aspartate aminotransferase ≥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) or activin signaling inhibitor for PAH at any time prior
to Baseline (use in vasoreactive testing is permitted).
13. Subjects currently on or who were treated with an inhaled or oral prostacyclin
pathway agent (iloprost, treprostinil, beraprost, or selexipag) for >6 months or
within 90 days prior to Baseline.
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. A subject
will not be excluded due to a positive drug screen caused by prescribed medications.
17. Initiation or discontinuation of a cardio-pulmonary rehabilitation program based
upon exercise within 90 days prior to Screening and/or planned during study
participation.
18. Prior participation in any study of ralinepag or participation in another
interventional clinical study with medicinal products within 30 days prior to
Screening. Concurrent participation in registry or observational studies is allowed,
as long as the subject can fulfill all other entry criteria and comply with all
study procedures.
19. Any reason that, in the opinion of the Investigator or Medical Monitor, precludes
the subject from participating in the study (eg, any previous or intercurrent
medical condition) that may increase the risk associated with study participation or
that would confound study analysis or impair study participation or cooperation.
20. Known hypersensitivity to ralinepag or any of the excipients.
21. Life expectancy <12 months based on the Investigator's opinion.
22. Women who are pregnant, lactating or breast-feeding.
- Connective Tissue Diseases
- Hypertension
- Lung Disease
- Lung Diseases
- Pulmonary Arterial Hypertension
- Pulmonary Hypertension