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A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03683186
Recruitment Status : Enrolling by invitation
First Posted : September 25, 2018
Last Update Posted : October 3, 2022
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Tracking Information
First Submitted Date  ICMJE September 19, 2018
First Posted Date  ICMJE September 25, 2018
Last Update Posted Date October 3, 2022
Actual Study Start Date  ICMJE September 23, 2019
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2019)
Number of subjects with treatment-emergent adverse events [Safety and Tolerability] [ Time Frame: Up to 6 years ]
The safety and tolerability of ralinepag will be evaluated by the Number of subjects with treatment-emergent adverse events
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
Safety as assessed by adverse events [ Time Frame: Up to 6 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
  • NT-proBNP [ Time Frame: Up to 6 years ]
  • 6-minute walk distance (6MWD) [ Time Frame: Up to 6 years ]
  • Heart rate recovery (HRR) following completion of 6-minute walk test (6MWT) [ Time Frame: Up to 6 years ]
  • WHO/New York Heart Association (NYHA) functional class [ Time Frame: Up to 6 years ]
  • Health-related quality of life (HRQoL) as measured by SF-36 [ Time Frame: Up to 6 years ]
  • HRQoL as measured by PAH-SYMPACT(R) [ Time Frame: Up to 6 years ]
  • Proportion of participants who achieve NT-proBNP level <300 pg/mL [ Time Frame: Up to 6 years ]
  • Proportion of participants who achieve WHO/NYHA functional class II status or better Proportion of participants who achieve 6MWD >440 meters [ Time Frame: Up to 6 years ]
  • Time to all-cause hospitalization [ Time Frame: Up to 6 years ]
  • Time to all-cause mortality [ Time Frame: Up to 6 years ]
  • Time to protocol-defined clinical failure event [ Time Frame: Up to 6 years ]
    Clinical failure events are defined as death, hospital admission for worsening PAH, disease progression, or unsatisfactory long-term clinical response.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
Official Title  ICMJE A Phase 3 Open-label Extension (OLE) Study to Evaluate the Long-term Safety and Efficacy of Ralinepag in Subjects With World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH)
Brief Summary Study ROR-PH-303, ADVANCE EXTENSION, is an open-label extension (OLE) study for participants with WHO Group 1 PAH who have participated in another Phase 2 or Phase 3 study of ralinepag.
Detailed Description

Study ROR-PH-303 is a multicenter, open-label extension (OLE) study for subjects with WHO Group 1 PAH who have participated in another Phase 2 or Phase 3 study of ralinepag and who qualify for entry based upon participation in the prior study. Subjects who discontinue participation in a prior study due to safety issues related to study medication or who fail to complete study procedures will not be eligible to enter Study ROR-PH-303. Subjects who meet all OLE entry criteria will be enrolled and will receive ralinepag in addition to their pre-existing PAH disease-specific background therapy.

For subjects who are enrolled from an ongoing double-blind Phase 2 or Phase 3 ralinepag study, a 16-week blinded Dose Titration Period will be completed following enrollment into the OLE. Subjects previously on ralinepag will continue on the same dose during the Dose Titration Period as received in the original study and will also initiate placebo treatment in the OLE.

Subjects who are enrolled from a non-blinded study or another OLE will not participate in the blinded Dose Titration Period in Study ROR-PH-303 but will be enrolled directly into the Treatment Period and continue on the dose of ralinepag received in the original study.

All subjects will receive ralinepag in the OLE study until premature discontinuation of ralinepag due to an AE/serious adverse event (SAE) or other reason, marketing approval of ralinepag is granted in the region in which the study is conducted, or the study is discontinued by the Sponsor.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • PAH
  • Pulmonary Hypertension
  • Pulmonary Arterial Hypertension
  • Hypertension
  • Connective Tissue Diseases
  • Familial Primary Pulmonary Hypertension
  • Vascular Diseases
  • Cardiovascular Diseases
  • Hypertension, Pulmonary
  • Lung Diseases
  • Respiratory Tract Disease
Intervention  ICMJE Drug: Ralinepag
Active
Other Name: APD811
Study Arms  ICMJE Experimental: Ralinepag
Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose.
Intervention: Drug: Ralinepag
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: September 21, 2018)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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.
  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 medically acceptable method of contraception 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 ralinepag.

Exclusion Criteria:

  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), or are lactating or breastfeeding.
  4. Subjects who have undergone lung or heart/lung transplant or the initiation of long-term parenteral or inhaled therapy with a prostacyclin during the time since participation in their original ralinepag study.
  5. Subjects who had an emergency unblinding procedure in a prior Phase 2 or 3 study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Chile,   China,   Croatia,   Czechia,   Denmark,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Portugal,   Romania,   Serbia,   Singapore,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Sweden
 
Administrative Information
NCT Number  ICMJE NCT03683186
Other Study ID Numbers  ICMJE ROR-PH-303
APD811-303 ( Other Identifier: Arena Pharmaceuticals )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party United Therapeutics
Original Responsible Party Arena Pharmaceuticals
Current Study Sponsor  ICMJE United Therapeutics
Original Study Sponsor  ICMJE Arena Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account United Therapeutics
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP