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. (RESTORE)

Phase 4

Completed

• Conditions: PAH; pulmonary arterial hypertension; 10024967; 10057166

• Registration Number: NL-OMON52455
• Lead Sponsor: Actelion Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

1.Signed informed consent prior to any study-mandated procedure
2.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% and 60% respectively.
3.PAH etiology belonging to one of the following groups according to
classification:
• Idiopathic PAH
• Heritable PAH
• Drugs or toxins induced
• PAH associated with connective tissue disease
• PAH associated with congenital heart disease, with simple
systemic-topulmonary shunt at least 1 year after surgical repair
4.First hemodynamic diagnosis of PAH by right heart catheterization (RHC)
within 12 months prior to initiation of selexipag, showing:
• mPAP >=25 mmHg and
• PA wedge pressure (PAWP) or LV end-diastolic pressure <=15 mmHg
and
• PVR >5 WU (400 dyn.s.cm-5) and
• RVSV <= 60 mL as shown in RHC (CO/HR)
5. Patients already receiving PAH-specific oral mono or dual therapy (ie,
phosphodiesterase type 5 inhibitors (PDE-5i) or soluble guanylate cyclase
stimulators (sGCs) and/or ERA) or patients who are not candidates for these
therapies. If on oral PAH-specific therapy, treatment has to be stable (ie, no
introduction of new therapies or changes in dose) for at least 90 days prior to
both ICF signature and Day 1
6.NT-proBNP >=300 ng/L at screening
7.Men or women >=18 years (or the legal age of consent in the jurisdiction in
which the study is taking place if greater than 18) and <65 years
8.Women of childbearing potential (Section 10.5) must meet the following
criteria:
• Have a negative serum pregnancy test during screening and a negative urine
pregnancy test on Day 1, and
• Agree to use reliable methods of contraception from Day 1 to at least 30 days
after study intervention discontinuation (Section 10.5), and
• If only using hormonal contraception, have used it for at least 1 month (30
days) before Day 1, and
• Agree to perform monthly pregnancy tests to at least 30 days after study
intervention discontinuation
9. 6MWD >=150 m during screening period

Exclusion Criteria

1.Prior use of 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
2.Treatment with strong inhibitors of CYP2C8 (eg, gemfibrozil) within 28 days
prior to Day 1
3.Treatment with another investigational drug planned or taken within 12 weeks
(84 days) prior to Day 1
4.Cardiopulmonary rehabilitation programs based on exercise between informed
consent and expected Week 26 visit date
5.Decompensated cardiac failure requiring hospitalization, emergency room visit
or intravenous diuretics in the 6 weeks before informed consent
6.Severe coronary heart disease or unstable angina
7.Cerebrovascular events (eg, transient ischemic attack, stroke) within 3
months prior to Day 1
8.Left atrial volume indexed for body surface area >=43 mL/m2, assessed
by Echo or cardiac MRI
9.Myocardial infarction within 6 months prior to Day 1
10.Body mass index >40 kg/m2 or body weight <40 kg
11.Presence of one or more of the following signs of relevant lung disease at
any time up to Day 1 - if pulmonary function test results are missing, then
exclusion 11 is considered as met • Diffusing capacity of the lung for carbon
monoxide <40% of predicted UNLESS computed tomography reveals no or mild
interstitial lung disease
• Forced vital capacity <60% of predicted
• Forced expiratory volume in 1 second <60% of predicted
12.Known or suspected pulmonary veno-occlusive disease (PVOD)
13.Congenital or acquired valvular defects with clinically relevant myocardial
function disorders not related to pulmonary hypertension
14. SBP <90 mmHg at screening or on Day 1
15.Severe renal impairment (estimated creatinine clearance <=30 mL/min/1.73 m2
or serum creatinine >2.5 mg/dL at screening) or ongoing or planned dialysis
16. Known and documented moderate or severe hepatic impairment (with or without
cirrhosis) at screening, defined as Child-Pugh Class C
17.Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism)
18.Any hospitalization within 6 weeks prior to informed consent (except
elective hospitalizations for surgery or standard monitoring of preexisting
conditions that did not worsen)
19.Concomitant life-threatening disease with a life expectancy of less than 12
months
20.Hemoglobin <80 g/L at screening
21.Hypersensitivity to selexipag or any study intervention excipient (mannitol,
maize starch, hydroxypropylcellulose, magnesium stearate,
hypromellose, propylene glycol, titanium dioxide, carnauba wax, iron oxide red,
iron oxide yellow, iron oxide black)
22.Pregnancy, breastfeeding, or intention to become pregnant during the study.
23.Any factor or condition likely to affect compliance with study intervention
or visit plan, as judged by the investigator
24.Claustrophobia
25.MRI-incompatible permanent cardiac pacemaker, automatic internal cardioverter
26.Metallic implant (eg, defibrillator, neurostimulator, hearing aid, permanent
use of infusion device, dental brace, metal-containing tattoo
ink)
27.Severe arrythmia, atrial fibrillation, multiple premature ventricular or
atrial contractions, or any other condition that would interfere with
proper cardiac gating du

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change from baseline to Week 26 in RV stroke volume (RVSV) assessed by<br /><br>pulmonary artery flow magnetic resonance imaging (MRI). </p><br>