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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

United Therapeutics Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

16 May 2019 → ongoing

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

United Therapeutics Corp.

External identifiers

EU CT number

2023-509305-68-00

EudraCT number

2018-001189-40

ClinicalTrials.gov

NCT03683186

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacokinetic

To evaluate the long-term safety and tolerability of ralinepag (APD811) in subjects who participated in a preceding Phase 2 or Phase 3 study of ralinepag.

Secondary objectives 1

1. The secondary objectives of the study are to evaluate the long-term effects of ralinepag on the following parameters: • N-terminal pro-brain natriuretic peptide • 6-Minute Walk Distance • WHO/New York Heart Association Functional Class • Health-related quality of life measures • Time to all-cause hospitalization • Time to all-cause mortality

Conditions and MedDRA coding

Pulmonary arterial hypertension (PAH)

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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 clinic visits, treatment plans, 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, in vitro fertilization) during the study and for 30 days after the last dose of ralinepag. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of ralinepag.

Exclusion criteria 8

1. Subjects who prematurely discontinued ralinepag 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 the initiation of long-term (>12 weeks) parenteral (intravenous or subcutaneous 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. Subjects who had an emergency unblinding procedure in a prior Phase 2 or 3 study.
7. Known hypersensitivity to ralinepag or any of the excipients.
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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): o NT-proBNP level <300 pg/mL o 6MWD >440 meters o 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

United Therapeutics Corp.

Sponsor organisation

United Therapeutics Corp.

Address

55 TW Alexander Drive

City

Durham

Postcode

27713-2847

Country

United States

Scientific contact point

Organisation

United Therapeutics Corp.

Contact name

Regulatory Department

Public contact point

Organisation

United Therapeutics Corp.

Contact name

Global Medical Information

Third parties 6

Locations

15 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 167 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications