Back to resultsA Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging (RESTORE)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Active
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
JNJ-67896049
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Right ventricle, Reverse remodeling, Magnetic resonance Imaging
Eligibility Criteria
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
Sites / Locations
- University Of California San Diego
- AnMed Health
- UT Southwestern
- Hospital Italiano de Buenos Aires
- Sanatorio Ramon Cereijo
- Instituto Cardiovascular de Buenos Aires
- Associacao Hospitalar Moinhos de Vento
- Irmandade Santa Casa de Misericordia de Porto Alegre
- Hospital Das Clinicas Da Faculdade De Medicina Da USP
- SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
- CHU Grenoble
- DRK Kliniken Westend
- Universitatsklinikum Bonn
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- Grantham Hospital
- Queen Mary Hospital, University of Hong Kong
- Hadassah Medical Center
- Rabin Medical Center, Beilinson Campus
- Chungnam National University Hospital
- Gachon University Gil Medical Center
- Seoul National University Hospital
- Asan Medical Center
- Samsung Medical Center
- Institut Jantung Negara
- VUMC Amsterdam
- Radboud Umcn
- National Medical Research Center of Cardiology of MoH of Russian Federation
- Federal State Budgetary Institution
- King Faisal Specialist Hospital & Research Center
- National Heart Centre (NHC) Singapore
- Tan Tock Seng Hospital
- Cleveland Clinic Abu Dhabi
- Golden Jubilee National Hospital
- Royal Free Hospital
- Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JNJ-67896049
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Number of Participants with AEs of Special Interest
Number of participants with AEs of special interest will be reported.
Number of Participants with Treatment-Emergent Marked Laboratory Abnormalities
Number of participants with treatment-emergent marked laboratory abnormalities will be reported.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04435782
Brief Title
A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging
Acronym
RESTORE
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 7, 2021 (Actual)
Primary Completion Date
July 28, 2023 (Actual)
Study Completion Date
August 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Right ventricle, Reverse remodeling, Magnetic resonance Imaging
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
JNJ-67896049
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
JNJ-67896049
Other Intervention Name(s)
Selexipag
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI)
Description
Change from baseline to week 26 in RVSV in participants will be assessed by pulmonary artery flow MRI.
Time Frame
Baseline and week 26
Secondary Outcome Measure Information:
Title
Change from Baseline to Week 26 in RV End-Diastolic Volume (RVEDV) Assessed by MRI
Description
Change from baseline to week 26 in RVEDV will be assessed by MRI.
Time Frame
Baseline and week 26
Title
Change from Baseline to Week 26 in RV End-Systolic Volume (RVESV) Assessed by MRI
Description
Change from baseline to week 26 in RVESV will be assessed by MRI.
Time Frame
Baseline and week 26
Title
Change from Baseline to Week 26 in RV Ejection Fraction (RVEF) Assessed by MRI
Description
Change from baseline to week 26 in RVEF will be assessed by MRI.
Time Frame
Baseline and week 26
Title
Change from Baseline to Week 26 in RV Mass Assessed by MRI
Description
Change from baseline to week 26 in RV mass will be assessed by MRI.
Time Frame
Baseline and week 26
Title
Change from Baseline to Week 26 RV Global Longitudinal Strain (RVGLS) Assessed by MRI
Description
Change from baseline to week 26 RVGLS will be assessed by MRI.
Time Frame
Baseline and week 26
Title
Change of Baseline to Week 26 in World Health Organization Functional Class (WHO FC)
Description
Change of baseline to week 26 in WHO FC in participants will be assessed.
Time Frame
Baseline and week 26
Title
Change form Baseline to Week 26 in N-Terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP)
Description
Change from baseline to week 26 NT-proBNP in participants will be assessed.
Time Frame
Baseline and week 26
Title
Change from Baseline to Week 26 in 6-Minute Walk Distance (6MWD)
Description
Change from baseline to week 26 in 6MWD in participants will be assessed.
Time Frame
Baseline and week 26
Title
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Up to 56 weeks
Title
Number of Participants with Serious Adverse Events (SAEs)
Description
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.
Time Frame
Up to 60 weeks
Title
Number of Participants with AEs Leading to Premature Discontinuation of Selexipag
Description
Number of participants with AEs leading to premature discontinuation of study drug Selexipag will be reported.
Time Frame
Up to 52 weeks
Title
Number of Participants with AEs of Special Interest
Description
Number of participants with AEs of special interest will be reported.
Time Frame
Up to 60 weeks
Title
Number of Participants with Treatment-Emergent Marked Laboratory Abnormalities
Description
Number of participants with treatment-emergent marked laboratory abnormalities will be reported.
Time Frame
Up to 56 weeks
Title
Change from Baseline to Week 26 in Number of Non-Invasive Low-Risk Criteria Variable
Description
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.
Time Frame
Baseline to week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Actelion Clinical Trial
Organizational Affiliation
Actelion
Official's Role
Study Director
Facility Information:
Facility Name
University Of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
AnMed Health
City
Anderson
State/Province
South Carolina
ZIP/Postal Code
29621
Country
United States
Facility Name
UT Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Hospital Italiano de Buenos Aires
City
Caba
ZIP/Postal Code
1199ABB
Country
Argentina
Facility Name
Sanatorio Ramon Cereijo
City
Caba
ZIP/Postal Code
C1048AAN
Country
Argentina
Facility Name
Instituto Cardiovascular de Buenos Aires
City
Ciudad Autonoma Buenos Aires
ZIP/Postal Code
1428
Country
Argentina
Facility Name
Associacao Hospitalar Moinhos de Vento
City
Porto Alegre
ZIP/Postal Code
90035-001
Country
Brazil
Facility Name
Irmandade Santa Casa de Misericordia de Porto Alegre
City
Porto Alegre
ZIP/Postal Code
90035-074
Country
Brazil
Facility Name
Hospital Das Clinicas Da Faculdade De Medicina Da USP
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
City
São Paulo
ZIP/Postal Code
04024-002
Country
Brazil
Facility Name
CHU Grenoble
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
DRK Kliniken Westend
City
Berlin
ZIP/Postal Code
14050
Country
Germany
Facility Name
Universitatsklinikum Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Grantham Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Queen Mary Hospital, University of Hong Kong
City
Hong Kong
Country
Hong Kong
Facility Name
Hadassah Medical Center
City
Jerusalem
Country
Israel
Facility Name
Rabin Medical Center, Beilinson Campus
City
Petah Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Chungnam National University Hospital
City
Daejeon
ZIP/Postal Code
35015
Country
Korea, Republic of
Facility Name
Gachon University Gil Medical Center
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Institut Jantung Negara
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
VUMC Amsterdam
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Radboud Umcn
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
National Medical Research Center of Cardiology of MoH of Russian Federation
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
Federal State Budgetary Institution
City
St Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
King Faisal Specialist Hospital & Research Center
City
Riyadh
ZIP/Postal Code
12713
Country
Saudi Arabia
Facility Name
National Heart Centre (NHC) Singapore
City
Singapore
ZIP/Postal Code
169609
Country
Singapore
Facility Name
Tan Tock Seng Hospital
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Facility Name
Cleveland Clinic Abu Dhabi
City
Abu Dhabi
ZIP/Postal Code
112412
Country
United Arab Emirates
Facility Name
Golden Jubilee National Hospital
City
Glasgow
ZIP/Postal Code
G81 4HX
Country
United Kingdom
Facility Name
Royal Free Hospital
City
Hampstead
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
City
Sheffield
ZIP/Postal Code
S10 2RX
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging
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