A study evaluating the efficacy and safety of ralinepag in treatment of patients with pulmonary hypertension.
- Conditions
- pulmonary arterial hypertension (PAH)MedDRA version: 20.0Level: LLTClassification code 10077731Term: Pulmonary hypertension WHO functional class ISystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-001187-33-GB
- Lead Sponsor
- nited Therapeutics Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 700
Each subject must meet ALL of the following inclusion criteria to be eligible for enrollment into the study:
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 classified by one of the following subgroups:
a. Idiopathic pulmonary arterial hypertension (IPAH);
b. Heritable pulmonary arterial hypertension (HPAH);
c. Drugs or toxins 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 shunt (must have undergone surgical correction at least 1 year prior to Screening and have no, or a clinically insignificant, shunt fraction [1.0 =pulmonary-systemic flow ratio (Qp/Qs) =1.5]) in the opinion of the Investigator.
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, 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 [LVEDP] =15 mmHg)
c. PVR >3.00 Wood units (=240 dynes/sec/cm5).
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 PDE5-I or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatments; however, 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 as needed for erectile dysfunction, up to 3 doses per week, is permitted. The subject should not have taken a dose within 48-hours of any Baseline or study related efficacy assessment.
8. Has a 6MWD of =150 meters.
9. If the subject is taking concomitant medications that may affect PAH (e.g., calcium channel blockers, digoxin, or L-arginine supplementation), 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.
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 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 (i.e., actively attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 30 days after the last dose of IMP.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 560
F.1.3 Elde
Subjects must not meet ANY of the following exclusion criteria to be eligible for enrollment into the study, unless otherwise indicated:
1. For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Baseline.
2. Subjects must not have 3 or more of the following left ventricular dysfunction risk factors:
a. Body mass index (BMI) =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. Any chronic atrial fibrillation.
3. 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 (FEV1) <60% (predicted); or
b. Total lung capacity (TLC) <60% predicted.
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 recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay (IVCD) will be excluded if the QTcF is >500 msec for both males and females.
7. Severe chronic liver disease (i.e., Child-Pugh C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (e.g., 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 (e.g., epoprostenol, treprostinil, or iloprost) 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).
-Subject is not eligible if treatment was stopped for a safety or tolerability issue 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 PAH specific background oral therapy) for at least 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 dru
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method