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

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

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

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: JNJ-67896049

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1199ABB
    • Hospital Italiano de Buenos Aires
  • Caba, Argentina, C1048AAN
    • Sanatorio Ramon Cereijo
  • Ciudad Autonoma Buenos Aires, Argentina, 1428
    • Instituto Cardiovascular de Buenos Aires
• Brazil
  • Porto Alegre, Brazil, 90035-074
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90035-001
    • Associacao Hospitalar Moinhos de Vento
  • Sao Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da USP
  • Sao Paulo, Brazil, 04024 002
    • SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
• France
  • La Tronche, France, 38700
    • CHU Grenoble
• Germany
  • Berlin, Germany, 14050
    • DRK Kliniken Westend
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg Universität Mainz
• Hong Kong
  • Hong Kong, Hong Kong
    • Grantham Hospital
  • Hong Kong, Hong Kong
    • Queen Mary Hospital University of Hong Kong
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center Beilinson Campus
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VUMC Amsterdam
  • Nijmegen, Netherlands, 6525 GA
    • Radboud Umcn
• Russian Federation
  • Moscow, Russian Federation, 121552
    • National Medical Research Center of Cardiology of MoH of Russian Federation
  • St Petersburg, Russian Federation, 197341
    • Federal State Budgetary Institution
• Saudi Arabia
  • Riyadh, Saudi Arabia, 12713
    • King Faisal Specialist Hospital & Research Center
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 169609
    • National Heart Centre (NHC) Singapore
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates, 112412
    • Cleveland Clinic Abu Dhabi
• United Kingdom
  • Glasgow, United Kingdom, G81 4HX
    • Golden Jubilee National Hospital
  • Hampstead, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • Sheffield, United Kingdom, S10 2RX
    • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • Texas
    • Dallas, Texas, United States, 75231
      • UT Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-67896049; Participants will receive JNJ-67896049 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.	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.; Other Names: Selexipag

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 assessed by pulmonary artery flow MRI was reported.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI	Change from baseline to Week 26 in RVEDV assessed by MRI was reported.	Baseline, Week 26
Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI	Change from baseline to Week 26 in RVESV assessed by MRI was reported.	Baseline, Week 26
Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI	Change from baseline to Week 26 in RVEF assessed by MRI was reported. RVEF was the fraction of the end-diastolic volume (EDV) that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction.	Baseline, Week 26
Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI	Change from baseline to Week 26 in RV mass index assessed by MRI was reported.	Baseline, Week 26
Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI	Change in RVGLS was a measure of longitudinal percent change in length of endocardium at Week 26 from baseline length assessed by MRI.	Baseline, Week 26
Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class	WHO functional classification for PAH ranged from Class I (no limitation in physical activity, ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope), Class II (slight limitation of physical activity, ordinary physical activity cause undue dyspnea or fatigue, chest pain or near syncope), Class III (marked limitation of physical activity, less than ordinary activity cause undue dyspnea or fatigue, chest pain or near syncope) and Class IV (cannot perform a physical activity without any symptoms, dyspnea and/or fatigue may even be present at rest). Change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement =reduction in functional class; worsened =increase in functional class; and no change = no change in functional class.	Baseline, Week 26
Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP)	NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy.	Baseline, Week 26
Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD)	6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.	Baseline, Week 26
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. Any AE occurring at or after the initial administration of study intervention up to 3 days after last dose of study intervention was considered as treatment-emergent.	Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days)
Number of Participants With Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug	Number of participants with AEs leading to premature discontinuation of study drug were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Day 1 up to last dose of study drug (up to Week 52)
Number of Participants With Adverse Events of Special Interest (AESI)	Number of participants with AESI were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESI were anaemia, bleeding events, gastrointestinal disturbances denoting intestinal intussusception (manifested as ileus or obstruction), hyperthyroidism, hypotension, light-dependent non-melanoma skin malignancies, major adverse cardiovascular events (MACE), medication errors, ophthalmological effects associated to retinal vascular system, pregnancy, pulmonary venoocclusive disease associated with pulmonary oedema, renal function impairment / acute renal failure.	Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days)
Number of Participants With Treatment-Emergent Marked Laboratory Abnormalities	Number of participants with treatment-emergent marked laboratory abnormalities in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, creatinine, sodium, potassium, hemoglobin, hematocrit; EVF; PCV (male), hematocrit; EVF; PCV (female), platelets (assuming no platelet cluster), leukocytes; white blood cells, Neutrophils (Abs), Eosinophils (Abs), lymphocytes (Abs) were reported. Abnormalities that occurred after study treatment start and up to 3 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Treatment-emergent marked laboratory abnormalities were determined at the investigator's discretion.	Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days)
Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables	The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 8 variables: absence of clinical signs of right heart failure, absence of symptoms progression, absence of syncope, WHO FC I-II, 6MWD greater than (>) 440 meter, NT-proBNP less than (<) 300 ng/L, Right atrial (RA) area <18 centimeter square (cm^2) as determined by echocardiography (Echo), absence of pericardial effusion, as determined by Echo. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 8 variables for each participant can vary from 0 (worse participants) to 8 (healthier participants). Higher score indicated healthier participants.	Baseline, Week 26
Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables	The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 3 variables: WHO FC I-II, 6MWD >440 m, NT-proBNP < 300 ng/L. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 3 variables for each participant can vary from 0 (worse participants) to 3 (healthier participants). Higher score indicated healthier participants.	Baseline, Week 26

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Actelion Clinical Trial, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): July 28, 2023

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Right ventricle; Reverse remodeling; Magnetic resonance Imaging
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; Familial Primary Pulmonary Hypertension; Ventricular Remodeling; Antihypertensive Agents; Selexipag
• Other Study ID Numbers: CR108753; 67896049PAH4005 (Other Identifier: Actelion); 2019-004783-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No