A multicenter, randomized, double-blind, placebo-controlled, parallel-group, group-sequential, adaptive, Phase 3 study with open-label extension period to assess the efficacy and safety of selexipag as an add-on to standard of care therapy in subjects with inoperable or persistent/recurrent after surgical and/or interventional treatment Chronic Thromboembolic Pulmonary Hypertension.
- Conditions
- Chronic Thromboembolic Pulmonary HypertensionCTEPH10037454
- Registration Number
- NL-OMON49441
- Lead Sponsor
- Actelion Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Signed and dated ICF.
2. Male and female subjects >=18 (or the legal age of consent in the
jurisdiction in which the study is taking place) and <= 85 years old at
screening (visit 1)
3. Subjects with diagnosis of CTEPH and inoperability confirmed by the
corresponding adjudication committee (AC; country-specific adjudication
committee [CSAC] or
central adjudication committee [CAC]), defined as one of the following options:
a) Inoperable CTEPH (i.e., technically non-operable) with:
- Diagnosis of CTEPH based on at least two of the following assessments
performed in the 14-month period prior to randomization (Visit 2):
ventilation/perfusion (V/Q) scan; pulmonary angiography (PA); computed
tomography pulmonary angiogram (CTPA) and/or magnetic resonance angiography
(MRA).
- RHC (and LHC if needed) 1 performed at least 90 days after start of full
anticoagulation showing: PVR at rest >= 400 dyn.sec/cm5 or >= 5 Wood units for
the hemodynamic cohort and PVR at rest >= 300 dyn.sec/cm5 or >=3.75 Wood units
for the non-hemodynamic cohort
- mean pulmonary arterial pressure (mPAP) >= 25 mmHg;
- Pulmonary arterial wedge pressure (PAWP) <= 15 mmHg or, if not available or
unreliable, a left ventricular end diastolic pressure (LVEDP) <= 15 mmHg.
b) Persistent/recurrent CTEPH after BPA and deemed inoperable, with:
- Diagnosis of CTEPH based on at least one of the following assessments
performed in the 14-month period prior to randomization (Visit 2) and after
last interventional (BPA) treatment: V/Q scan, PA, CTPA or MRA.
- RHC (and LHC if needed)performed at least 90 days after last interventional
(BPA) treatment and at least 90 days after start of full anticoagulation,
showing:
PVR at rest >= 400 dyn.sec/cm5 or >= 5 Wood units for the hemodynamic cohort and
PVR at rest >=300 dyn.sec/cm5 or >=3,75 Wood units for the non-hemodynamic
cohort;
mPAP >= 25 mmHg;
PAWP <= 15 mmHg, or, if not available or unreliable, an LVEDP <= 15 mmHg.
c) Persistent/recurrent CTEPH after PEA (including PEA followed by BPA) with:
- Diagnosis of CTEPH based on at least one of the following assessments
performed in the 14-month period prior to randomization (Visit 2) and after
last surgical (PEA) or interventional (BPA) treatment: V/Q scan, PA, CTPA or
MRA.
-RHC (and LHC if needed) performed at least 90 days after last surgical (PEA)
or interventional (BPA) treatment and at least 90 days after start of full
anticoagulation, showing: PVR at rest >= 400 dyn.sec/cm5 or 5 Wood units for the
hemodynamic cohort and PVR at rest >=300 dyn.sec/cm5 or >=3,75 Wood units for the
non-hemodynamic cohort;
mPAP >= 25 mmHg;
PAWP <= 15 mmHg, or, if not available or unreliable, an LVEDP <= 15 mmHg.
4. PH in WHO FC I-IV.
5. Subject able to perform the 6MWT with a minimum distance of 100 m and a
maximum distance of 450 m at screening visit (Visit 1).
6. A woman of childbearing potential [see definition in Section 4.5.1] is
eligible only if all the following applies:
a. Negative serum pregnancy test at Screening and a negative urine pregnancy
test at randomization.
b. Agreement to undertake monthly urine pregnancy tests during the study and up
to at least 30 days after study treatment discontinuation.
c. Agreement to use one of the methods of birth control described in Section
4.5 from Screening v
1. Planned BPA within 26 weeks after randomization.
2. Change in dose or initiation of new PH-specific therapy within 90 days prior
to the baseline RHC (and LHC if needed) qualifying for enrollment for the
hemodynamic cohort and within 90 days prior to randomization (Visit 2) for the
non-hemodynamic cohort
3. Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e.,
treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e.,
selexipag/Uptravi) within 90 days prior to randomization (Visit 2), except
those given at vasodilator testing during RHC
4. Change in dose or initiation of new diuretics and/or calcium channel
blockers within 1 week prior to baseline RHC (and LHC if needed).
Exclusion criteria related to comorbidities
5. Severe coronary heart disease or unstable angina as assessed by the
investigator.
6. Myocardial infarction within the last 6 months prior to screening.
7. Decompensated cardiac failure if not under close supervision.
8. Severe arrhythmias as assessed by the investigator.
9. Cerebrovascular events (e.g., transient ischemic attack, stroke) within the
last 3 months prior to screening.
10. Congenital or acquired valvular defects with clinically relevant myocardial
function disorders not related to pulmonary hypertension.
11. Known or suspicion of pulmonary veno-occlusive disease. Exclusion criteria
related to selexipag use
12. Known and documented severe hepatic impairment.
13. Severe renal failure (estimated glomerular filtration rate < 30 mL/min/1.73
m2 or serum creatinine > 2.5 mg/dL) at screening.
14. Known or suspected uncontrolled thyroid disease as per investigator
judgment.
15. Pregnant, planning to be become pregnant or lactating.
16. Treatment with strong inhibitors of cytochrome P-450 2C8 (CYP2C8; e.g.,
gemfibrozil) within 14 days prior to randomization.
17. Systolic blood pressure < 90 mmHg at screening (Visit 1) or at
randomization (Visit 2).
18. Known hypersensitivity to selexipag or drugs of the same class, or any of
their excipients.
19. Planned or current treatment with another investigational treatment up to 3
months prior to randomization.
20. Any co-morbid condition that may influence the ability to perform a
reliable and reproducible 6MWT, including use of walking aids (cane, walker,
etc.).
21. Any known factor or disease that might interfere with treatment compliance,
study conduct or interpretation of the results, such as drug or alcohol
dependence or psychiatric disease.
22. Known concomitant life-threatening disease with a life expectancy < 12
months.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary efficacy endpoint(s):<br /><br>PVR (pulmonary vascular resistance) at Week 20, assessed at rest, within 2-5<br /><br>hours post dose, expressed as a percent of baseline PVR.<br /><br><br /><br>Timepoint(s) of evaluation of this end point<br /><br>Assessed at rest in screening period (Day -60 to Day -14; baseline) and<br /><br>assessed at rest within 2-5 hours post-dose at Week 20 during<br /><br>treatment period.</p><br>
- Secondary Outcome Measures
Name Time Method