A study evaluating the efficacy and safety of ralinepag in treatment of patients with pulmonary hypertension.

Phase 1

• Conditions: pulmonary arterial hypertension (PAH); MedDRA version: 20.0Level: LLTClassification code 10077731Term: Pulmonary hypertension WHO functional class ISystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-001187-33-PL
• Lead Sponsor: nited Therapeutics Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-12-06
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

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;
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.
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, 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).
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 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.
8. Has a 6MWD of =150 meters.
9. If the subject is taking concomitant medications that may affect the
clinical manifestations of PAH (e.g., calcium channel blockers, diuretics,
digoxin, or L-arginine supplementation, beta blockers, angiotensinconverting
enzyme inhibitors, or angiotensin II receptor blockers), the
subject must be on a stable dose for at least 30 days prior to theBaseline Visit and the dosage mainta, 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.
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 (ie, actively attempt to become
pregnant or to impr

Exclusion Criteria

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 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 =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 infraction 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.
3. Has evidence of more than mild parenchymal 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.
4. 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.
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 (IVCD). In the presence of IVDC, subjects, defined as a QRS interva greater than 110 msec, will be excluded in 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 =3 times the upper limit of normal (ULN) or total bilirubin =2 × ULN at Screening.
10. Chronic renal insufficiency as defined by serum creatinine >2.5mg/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) 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.
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 is 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified