BridgeMD
A study evaluating the efficacy and safety of ralinepag in treatment of patients with pulmonary arterial hypertension.
EU CTIS ID: 2023-509304-16-00
What this study is testing
The primary objective of this study is to demonstrate the effect of ralinepag on the time to first adjudicated protocol-defined clinical worsening event in subjects with PAH.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- At least 18 years of age
- Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through 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 (ie, actively attempt to become pregnant or to impregnate, in vitro fertilization) 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.
- 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.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Primary diagnosis of symptomatic PAH classified by one of the following subgroups: a. Idiopathic pulmonary arterial hypertension; b. Heritable pulmonary arterial hypertension; c. Drug or toxin induced based on prior exposure to drugs, chemicals, or toxins, such as fenfluramine derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan. d. PAH associated with: Connective tissue disease (CTD), HIV infection; Congenital systemic pulmonary intracardiac shunt (must have undergone surgical correction or repair with a closure device at least 1 year prior to Screening and have no, or a clinically insignificant, shunt fraction [1.0 ≤pulmonary-systemic flow ratio ≤1.5] in the opinion of the Investigator.
- 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, meeting all of the following criteria: a. Mean pulmonary arterial pressure (mPAP) ≥20 mmHg (at rest) b. PAWP ≤15 mmHg (if PAWP cannot be reliably attained, then left ventricular end diastolic pressure ≤15 mmHg) c. PVR >2.00 Wood units (>160 dynes/sec/cm5).
You likely can't join if
- For subjects with known HIV-associated PAH, a cluster designation 4 T-cell count <200/mm3 within 90 days of Baseline.
- Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.
- Hemoglobin concentration <9 g/dL at Screening.
- Subjects treated with an IV or SC prostacyclin pathway agent (e.g., epoprostenol, treprostinil, or iloprost) or activin signaling inhibitor for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
- 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. Subject is not eligible if treatment was stopped for a safety or tolerability issue related to systemic prostacyclin adverse effects at any time. If a subject discontinued for other reasons, the subject may be eligible if the subject has been off therapy and stable (i.e., no change in WHO/NYHA FC or change in PAHspecific background oral therapy) for at least 90 days prior to Baseline.
- Subject has pulmonary veno-occlusive disease.
See the full eligibility criteria
Who can join
- At least 18 years of age
- Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through 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 (ie, actively attempt to become pregnant or to impregnate, in vitro fertilization) 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.
- 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.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Primary diagnosis of symptomatic PAH classified by one of the following subgroups: a. Idiopathic pulmonary arterial hypertension; b. Heritable pulmonary arterial hypertension; c. Drug or toxin induced based on prior exposure to drugs, chemicals, or toxins, such as fenfluramine derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan. d. PAH associated with: Connective tissue disease (CTD), HIV infection; Congenital systemic pulmonary intracardiac shunt (must have undergone surgical correction or repair with a closure device at least 1 year prior to Screening and have no, or a clinically insignificant, shunt fraction [1.0 ≤pulmonary-systemic flow ratio ≤1.5] in the opinion of the Investigator.
- 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, meeting all of the following criteria: a. Mean pulmonary arterial pressure (mPAP) ≥20 mmHg (at rest) b. PAWP ≤15 mmHg (if PAWP cannot be reliably attained, then left ventricular end diastolic pressure ≤15 mmHg) c. PVR >2.00 Wood units (>160 dynes/sec/cm5).
- Has WHO/NYHA functional class II to IV symptoms.
- If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist and/or a PDE5-I or a soluble guanylate cyclase (sGC) stimulator. Subjects must have access to locally available standard of care treatment in accordance with national guidelines a. Stable is defined as no change in dose or regimen within 30 days prior to Baseline and for the duration of the study. b. Subjects may be on either a PDE5 inhibitor or an sGC at stable dose (but not both). c. If the subject's disease-specific PAH therapy does not include a PDE-5 inhibitor, the use of PDE5-I for erectile dysfunction, up to 3 doses per week, is permitted.
- Has a 6MWD of ≥150 m.
- If the subject is taking concomitant medications that may affect the clinical manifestations of PAH (e.g., calcium channel blockers, diuretics, digoxin, L-arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), the subject 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.
What rules you out
- For subjects with known HIV-associated PAH, a cluster designation 4 T-cell count <200/mm3 within 90 days of Baseline.
- Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.
- Hemoglobin concentration <9 g/dL at Screening.
- Subjects treated with an IV or SC prostacyclin pathway agent (e.g., epoprostenol, treprostinil, or iloprost) or activin signaling inhibitor for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
- 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. Subject is not eligible if treatment was stopped for a safety or tolerability issue related to systemic prostacyclin adverse effects at any time. If a subject discontinued for other reasons, the subject may be eligible if the subject has been off therapy and stable (i.e., no change in WHO/NYHA FC or change in PAHspecific background oral therapy) for at least 90 days prior to Baseline.
- Subject has pulmonary veno-occlusive disease.
- 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.
- Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine on thein 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.
- 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 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.
- Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (e.g., 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.
- Subjects must not have 3 or more of the following left ventricular dysfunction risk factors: a. Body mass index ≥30 kg/m2 b. History of systemic hypertension c. Diabetes mellitus – any type d. Historical evidence of significant coronary artery disease established by any 1 of the following: History of myocardial infarction or percutaneous coronary intervention or angiographic evidence of coronary artery disease (>50% stenosis in at least 1 coronary artery); Positive stress test with imaging; Previous coronary artery bypass graft; angina e. Recurrent or persistent atrial fibrillation.
- 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
- Has evidence of more than mild lung disease on PFTs performed within 180 days prior to, or during Screening. Subjects with any of the following criteria will be excluded: a. Forced expiratory volume in 1 second <60% (predicted); or b. Total lung capacity (TLC) <60% (predicted)
- Has evidence of thromboembolic disease as determined by a V/Q lung scan or other 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.
- 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 (IVCD). In the presence of IVCD, subjects, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is >500 msec for both males and females.
- Severe chronic liver disease (i.e., Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (e.g., history of variceal hemorrhage, encephalopathy).
- Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.
The study team makes the final eligibility decision.
Where it's taking place
- China
- Singapore
- Australia
- Brazil
- United Kingdom
- United States
- Ukraine
- Mexico
- Argentina
- Serbia
- Taiwan
- Israel
- Korea, Republic of
- Canada
- Turkey
- Chile
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include China; Singapore; Australia; Brazil; United Kingdom; United States and 10 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.