A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging

Pulmonary Arterial Hypertension Clinical Trial

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Official title:

A Prospective, Multicenter, Single-Arm, Open-Label, Phase 4 Study of the Effects of Selexipag on Right Ventricular Remodeling in Pulmonary Arterial Hypertension Assessed by Cardiac Magnetic Resonance Imaging

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04435782
• Other study ID #: CR108753
• Secondary ID: 67896049PAH40052
• Status: Terminated
• Phase: Phase 4
• Start date: July 7, 2021
• Est. completion date: July 28, 2023

Study information

• Verified date: December 2023
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the effects of selexipag on right ventricular (RV) function in participants with Pulmonary arterial hypertension (PAH).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: July 28, 2023
• Est. primary completion date: July 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• World health organization functional class (WHO FC) II or III. Enrollment will be stratified by WHO FC II or III. Proportion of participants with WHO FC II and WHO FC III are expected to be approximately 40 percent (%) and 60%, respectively

• Pulmonary arterial hypertension (PAH) etiology belonging to one of the following groups according to 6th world symposium of pulmonary hypertension (WSPH) classification: a) Idiopathic PAH, b) Heritable PAH, c) Drugs or toxins induced d) PAH associated with connective tissue disease, e) PAH associated with congenital heart disease, with simple systemic-to-pulmonary shunt at least 1 year after surgical repair

• Patients already receiving PAH-specific oral mono or dual therapy (that is, phosphodiesterase type 5 inhibitors [PDE-5i] or soluble guanylate cyclase stimulators [sGCs] and/or endothelin receptor antagonist [ERA]) or patients who are not candidates for these therapies

• N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) greater than or equal to (>=) 300 nanograms per liter (ng/L) (greater than or equal to [>=] 300 picograms per milliliter [pg/mL]; >=35.5 picomoles per liter [pmol/L]) at screening

• Women of childbearing potential must meet the following criteria: a) Have a negative serum pregnancy test during screening and a negative urine pregnancy test on Day 1, b) Agree to use acceptable methods of contraception from Day 1 to at least 30 days after study intervention discontinuation, c) If only using hormonal contraception, have used it for at least 1 month (30 days) before Day 1, and d) Agree to perform monthly pregnancy tests to at least 30 days after study intervention discontinuation

• 6-minute walking distance (6MWD) >=150 meter (m) during screening period

Exclusion Criteria:

• Prior use of Prostacyclin (IP)-receptor agonist, prostacyclin, or prostacyclin analog. Use of such treatments for vasoreactivity testing is not exclusionary; intermittent use of such treatments for digital ulcers or Raynaud's phenomenon is not exclusionary if stopped > 6 months (180 days) prior to Day 1

• Treatment with strong inhibitors of CYP2C8 (example, gemfibrozil) within 4 weeks (28 days) prior to Day 1

• Treatment with another investigational drug planned or taken within 12 weeks (84 days) prior to Day 1

• Severe coronary heart disease or unstable angina

• Cerebrovascular events (example, transient ischemic attack, stroke) within 3 months (90 days) prior to Day 1

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension
• Ventricular Remodeling

Intervention

Drug:
• JNJ-67896049
Participants will receive tablets at a starting dose of 200 mcg on Day 1. Dose will be up-titrated from Day 1 to the end of Week 12 (Day 84) to determine individual maintenance dose (IMD). Then, participants will receive JNJ-67896049 tablets at their IMD from Week 13 to Week 52.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Caba
Argentina	Sanatorio Ramon Cereijo	Caba
Argentina	Instituto Cardiovascular de Buenos Aires	Ciudad Autonoma Buenos Aires
Brazil	Associacao Hospitalar Moinhos de Vento	Porto Alegre
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da USP	Sao Paulo
Brazil	SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo	São Paulo
France	CHU Grenoble	La Tronche
Germany	DRK Kliniken Westend	Berlin
Germany	Universitatsklinikum Bonn	Bonn
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Hong Kong	Grantham Hospital	Hong Kong
Hong Kong	Queen Mary Hospital University of Hong Kong	Hong Kong
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center, Beilinson Campus	Petah Tikva
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Institut Jantung Negara	Kuala Lumpur
Netherlands	VUMC Amsterdam	Amsterdam
Netherlands	Radboud Umcn	Nijmegen
Russian Federation	National Medical Research Center of Cardiology of MoH of Russian Federation	Moscow
Russian Federation	Federal State Budgetary Institution	St Petersburg
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Singapore	National Heart Centre (NHC) Singapore	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
United Arab Emirates	Cleveland Clinic Abu Dhabi	Abu Dhabi
United Kingdom	Golden Jubilee National Hospital	Glasgow
United Kingdom	Royal Free Hospital	Hampstead
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital	Sheffield
United States	AnMed Health	Anderson	South Carolina
United States	UT Southwestern	Dallas	Texas
United States	University Of California San Diego	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  France,  Germany,  Hong Kong,  Israel,  Korea, Republic of,  Malaysia,  Netherlands,  Russian Federation,  Saudi Arabia,  Singapore,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI)	Change from baseline to week 26 in RVSV in participants will be assessed by pulmonary artery flow MRI.	Baseline and week 26
Secondary	Change from Baseline to Week 26 in RV End-Diastolic Volume (RVEDV) Assessed by MRI	Change from baseline to week 26 in RVEDV will be assessed by MRI.	Baseline and week 26
Secondary	Change from Baseline to Week 26 in RV End-Systolic Volume (RVESV) Assessed by MRI	Change from baseline to week 26 in RVESV will be assessed by MRI.	Baseline and week 26
Secondary	Change from Baseline to Week 26 in RV Ejection Fraction (RVEF) Assessed by MRI	Change from baseline to week 26 in RVEF will be assessed by MRI.	Baseline and week 26
Secondary	Change from Baseline to Week 26 in RV Mass Assessed by MRI	Change from baseline to week 26 in RV mass will be assessed by MRI.	Baseline and week 26
Secondary	Change from Baseline to Week 26 RV Global Longitudinal Strain (RVGLS) Assessed by MRI	Change from baseline to week 26 RVGLS will be assessed by MRI.	Baseline and week 26
Secondary	Change of Baseline to Week 26 in World Health Organization Functional Class (WHO FC)	Change of baseline to week 26 in WHO FC in participants will be assessed.	Baseline and week 26
Secondary	Change form Baseline to Week 26 in N-Terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP)	Change from baseline to week 26 NT-proBNP in participants will be assessed.	Baseline and week 26
Secondary	Change from Baseline to Week 26 in 6-Minute Walk Distance (6MWD)	Change from baseline to week 26 in 6MWD in participants will be assessed.	Baseline and week 26
Secondary	Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAE is any AE from first dose up to 3 days after end of study intervention.	Up to 56 weeks
Secondary	Number of Participants with Serious Adverse Events (SAEs)	A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to 60 weeks
Secondary	Number of Participants with AEs Leading to Premature Discontinuation of Selexipag	Number of participants with AEs leading to premature discontinuation of study drug Selexipag will be reported.	Up to 52 weeks
Secondary	Number of Participants with AEs of Special Interest	Number of participants with AEs of special interest will be reported.	Up to 60 weeks
Secondary	Number of Participants with Treatment-Emergent Marked Laboratory Abnormalities	Number of participants with treatment-emergent marked laboratory abnormalities will be reported.	Up to 56 weeks
Secondary	Change from Baseline to Week 26 in Number of Non-Invasive Low-Risk Criteria Variable	Change from baseline to Week 26 in number of non-invasive low-risk criteria among the following 8 variables: Absence of clinical signs of right heart failure; Absence of symptoms progression; Absence of syncope; World Health Organization functional class (WHO FC) I-II; 6-minute walking distance (6MWD) greater than (>) 440 meters (m); N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) less than (<) 300 nanogram per liters (ng/L); Right atrial (RA) area <18 centimeter square (cm^2), as determined by echocardiography (Echo) and Absence of pericardial effusion, as determined by Echo will be assessed.	Baseline to week 26