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

  • STATUS
    Recruiting
  • End date
    Sep 1, 2023
  • participants needed
    193
  • sponsor
    United Therapeutics
Updated on 15 September 2021
exercise stress test
diuretics
cardiopulmonary exercise testing
stress test
endothelin
ralinepag
endothelin receptor antagonist

Summary

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

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. Subjects who discontinue study drug prior to Week 28, as well as those who complete Week 28 on study drug but choose not to participate in the OLE study, will be contacted every 6 months and at the end of the study to determine their survival status. Subjects who prematurely discontinue study drug or withdraw from the study for any reason will not be eligible to enter the OLE study.

Details
Condition Pulmonary Disease, Rheumatism, Vascular Diseases, CONNECTIVE TISSUE DISEASE, Respiratory Tract Diseases, Hypertension, Pulmonary Hypertension, Cardiovascular Disease, polycyclic aromatic hydrocarbons, Cancer Prevention, Surviving Abuse, Joint Injuries, Abdominal Surgery, Mental Disability, Pelvic Adhesions, Low Testosterone, Dental Filling, Habit Reversal, Complicated Grief, Diabetes and Hypertension, Chronic Pelvic Pain, Gambling Problems, Myopic Macular Degeneration, Nerve Injury, Severe Premenstrual Symptom, High Blood Pressure (Hypertension), High Blood Pressure (Hypertension - Pediatric), Dermatomyositis (Connective Tissue Disease), Stasis Dermatitis, Pulmonary Arterial Hypertension, Open Heart Surgery, Recurrent Pregnancy Loss, Effects of Chemotherapy, Renal Anemia, Functional Dyspepsia, Catheter Complications, Serial Evaluation of Ductal Epithelium, Chronic Renal Anemia, Cancer Treatment, Anemic Cancer, Spinocerebellar Disorders, Pseudobulbar Affect, Spine Athroplasty, Indikation: Diabetes - Typ II, Partial Medial Meniscectomy, Primary Insulin Hypersecretion, Testotoxikose, Infantile Fibrosarcoma, Late Infantile Neuronal Ceroid Lipfuscinsosis, Elevated Blood Pressure, Familial Primary Pulmonary Hypertension, Connective Tissue Diseases, Lung Disease, Memory Problems, vascular disorder, connective tissue disorder, p-aminohippuric acid, rheumatic disease, inflammatory rheumatism, collagen disorders, hpah, high blood pressure, arterial hypertension, pulmonary diseases, lung diseases, pulmonary disorders, cardiovascular diseases, cardiovascular disease (cvd), cardiovascular system diseases, cardiovascular disorders, vascular disease, vasculopathy, vasc, respiratory tract disease
Treatment Placebo, Ralinepag
Clinical Study IdentifierNCT04084678
SponsorUnited Therapeutics
Last Modified on15 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Signed informed consent form
At least 18 years of age
Primary diagnosis of PAH
Has had a diagnostic RHC performed at or within 3 years before Screening (or at Screening if one is not available) that is consistent with the diagnosis of PAH
Has World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) II to III symptoms
Has a 6-minute walk distance (6MWD) of 150 meters at Screening
Must be on a stable dose of PAH-specific oral therapy, defined as no change in dose or regimen for at least 120 days prior to randomization. Allowable PAH-specific therapy is an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator. Subjects may be on a stable dose of either a PDE5-I or a sGC stimulator, not both
Has a VE/VCO2 slope 38 during the Screening CPET, as assessed by the CPET core laboratory
Has a peak VO2 of 10 to <18 mLkg-1min-1 during the Screening CPET, as assessed by the CPET core laboratory
If the subject is taking concomitant medications that may affect the clinical manifestations of PAH, the subject must be on a stable dose for at least 30 days prior to randomization. The exception is that the dose of diuretics should remain stable for at least the 10 days prior to randomization and the dosage maintained throughout the study
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 Week 28 Visit/28-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 final dose of study drug. Eligible male subjects must agree not to participate in sperm donation for 90 days after the final dose of study drug
Women who are surgically sterile or postmenopausal are not considered to be of
childbearing potential. If of childbearing potential, female partners of male
study participants should agree to utilize medically acceptable methods of
contraception for the duration of study participation

Exclusion Criteria

Symptomatic coronary disease and/or myocardial infarction within past 6 months
Current symptomatic aortic or mitral valve disease
Requires use of supplemental oxygen during CPET
For subjects with known human immunodeficiency virus-associated PAH, a cluster designation of differentiation 4 (CD4+) T-cell count <200/mm3 at Screening
Has 3 or more left ventricular disease dysfunction risk factors
Acute non-cardiac disorder that may affect exercise performance or be aggravated by exercise (eg, infection, renal failure, thyrotoxicosis)
Has evidence of more than mild lung disease on pulmonary function tests performed within 1 year prior to, or during, Screening
Has evidence of thromboembolic disease as determined by ventilation-perfusion lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH
Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator
Respiratory exchange ratio <1.0 at Screening CPET as determined by the CPET core laboratory
Male subjects with a QTcF >450 msec and female subjects with a QTcF >470 msec on electrocardiogram (ECG) recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval >110 msec, will be excluded if QTcF is >500 msec for both males and females
Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis, or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy)
Confirmed active infection with hepatitis B virus or hepatitis C virus
Subjects with alanine aminotransferase or aspartate aminotransferase 3 times the upper limit of normal or total bilirubin 2 times the upper limit of normal at Screening
Chronic renal insufficiency as defined by an estimated glomerular filtration rate using the Modification of Diet in Renal Disease Study equation of <30 mL/min/1.73 m^2 or requiring dialysis at Screening
Hemoglobin concentration <9 g/dL at Screening
Subjects treated with an intravenous or subcutaneous prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) for PAH at any time (use in vasoreactive testing is permitted)
Subjects currently on or who have been treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) within 120 days prior to randomization
Subject has pulmonary veno-occlusive disease
Malignancy diagnosed and/or treated within 3 years of 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
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. Subjects will not be excluded due to a positive drug screen caused by prescribed medications
Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation
Prior participation in any study of ralinepag or another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, if the subject can fulfill all other entry criteria and comply with all study procedures
Any reason that, in the opinion of the Investigator, 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 (eg, right-to-left shunt detected during CPET) or impair study participation or cooperation
Known hypersensitivity to ralinepag or any of the excipients
Life expectancy <12 months based on the Investigator's opinion
Women who are pregnant, lactating, or breast-feeding
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