An open-label extension (OLE) study to evaluate the long-term safety and efficacy of ralinepag in patients with pulmonary arterial hypertension

• Register: EUCTR
• Last refreshed on: 3 November 2020
• Main ID: EUCTR2018-001189-40-HU
• Date of registration: 21/01/2019
• Prospective Registration: No
• Primary sponsor: United Therapeutics Corporation
• Public title: An open-label extension (OLE) study to evaluate the long-term safety and efficacy of ralinepag in patients with pulmonary arterial hypertension
• Scientific title: A study evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects with PAH via an Open-label Extension (ADVANCE-Extension) - ADVANCE-extension
• Date of first enrolment: 14/01/2019
• Target sample size: 1000
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001189-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: extension; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Denmark, European Union, France, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Poland, Portugal, Serbia, Singapore, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Regulatory Department
• Affiliation: United Therapeutics Corporation

• Name: Regulatory Department
• Affiliation: United Therapeutics Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
Each subject must meet ALL of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Completed the protocol-defined Study Drug Termination Visit or End of Study Visit procedures in the preceding ralinepag study.
4. 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; sperm donation; in vitro fertilization) during the study and for 30 days after the last dose of ralinepag.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
Eligible subjects must not meet ANY of the following exclusion criteria to be eligible for enrollment into the study:
1. Subjects who prematurely discontinued investigational medicinal product (IMP) due to a drug-related AE/SAE or tolerability issue in the preceding ralinepag study in which they were enrolled, or subjects who did not complete all protocol-defined study procedures at a Study Drug Termination Visit or End of Study Visit in the preceding ralinepag study.
2. Subjects who withdrew consent during participation in another ralinepag study.
3. Female subjects who wish to become pregnant or who have a positive pregnancy test on Day 1 (OLE Entry Visit).
4. Women who are pregnant, lactating, or breastfeeding
5. Subjects who have undergone lung or heart/lung transplant or are receiving longterm parenteral (intravenous [IV] or subcutaneous [SC] infusion) or inhaled therapy with a prostacyclin or oral therapy with another IP receptor agonist during the time since participation in their original ralinepag study.
6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with QTcF >470 msec on electrocardiogram (ECG) recorded within 12 weeks prior to Day 1.
7. Subjects who had an emergency unblinding procedure in a prior Phase 2 or 3 ralinepag study.
8. Known hypersensitivity to ralinepag or any of the excipients.
9. Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study, eg, noncompliance concerns, 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Pulmonary arterial hypertension (PAH)
MedDRA version: 20.0 Level: LLT Classification code 10077731 Term: Pulmonary hypertension WHO functional class I System Organ Class: 100000004855

Intervention(s)

Product Name: Ralinepag
Product Code: APD811
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Ralinepag
Product Code: APD811
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-

Product Name: Ralinepag
Product Code: APD811
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Main Objective: The primary objective of this study is:
To evaluate the long-term safety and tolerability of ralinepag (APD811) in subjects who have participated in a preceding Phase 2 or Phase 3 study of ralinepag.

Secondary Objective: The secondary objectives of the study are to evaluate the long-term effects of ralinepag on the following parameters:
• N-terminal pro b-type natriuretic peptide (NT-proBNP)
• 6-minute walk distance (6MWD)
• WHO/ New York Heart Association (NYHA) functional class (FC)
• Health-related quality of life (HRQoL) measures
• Time to all-cause hospitalization
• Time to all-cause mortality

Timepoint(s) of evaluation of this end point: Continuous endpoints (NT-proBNP, 6MWD, and HRQoL) and changes
from baseline will be summarized by visit.

Primary end point(s): Efficacy assessments will include an evaluation of:
• NT-proBNP
• 6MWD
• WHO/NYHA FC
• The proportion of subjects who achieve all 3 of the following (at
specified time points):
? NT-proBNP level <300 pg/mL
? 6MWD >440 meters
? WHO/NYHA FC II status or better
• HRQoL measures (where validated)
• Time to all-cause hospitalization during the study period
• Time to all-cause mortality during the study period

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: No

Secondary end point(s): No

Secondary ID(s)

2018-001189-40-FR

109021

ROR-PH-303(APD811-303)

Source(s) of Monetary Support

United Therapeutics Corporation

Ethics review

Status: Approved
Approval date: 27/12/2018
Contact: