A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 6 January 2025
• Main ID: NCT04271475
• Date of registration: 13/02/2020
• Prospective Registration: Yes
• Primary sponsor: Actelion
• Public title: A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension MACiTEPH
• Scientific title: A Prospective, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Adaptive Phase 3 Study With Open-label Extension to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension
• Date of first enrolment: July 7, 2020
• Target sample size: 127
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT04271475
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Bulgaria, Canada, China, Colombia, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Actelion Clinical Trial
• Affiliation: Actelion

Key inclusion & exclusion criteria

Inclusion Criteria:

- Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization
[WHO] Group 4) fulfilling one of the following criteria: a) inoperable due to the
localization of the obstruction being surgically inaccessible (that is, distal
disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA),
and deemed inoperable due to the localization of the obstruction being surgically
inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue
pulmonary endarterectomy (PEA)

- 6-minute walk distance (6MWD) greater than or equal to (>=) 100 meter (m) and less
than or equal to (<=) 450 meters (m), documented by an eligibility and a baseline
6-minute walk test (6MWT). The baseline 6MWD must not differ by more than 15 percent
(%) from the eligibility test

- World Health Organization functional class (WHO FC) >= II

- Participants are to receive riociguat as per local standard of care, unless it is
contraindicated or unavailable

Exclusion Criteria:

- Acute pulmonary embolism within 3 months prior to or during Screening

- Planned balloon pulmonary angioplasty (BPA) during the fixed duration part of the
double-blind period

- Significant obstructive and restrictive lung disease

- Acute or chronic conditions (other than dyspnea) that limit the ability to comply
with study requirements, in particular with 6MWT (for example, intermittent
claudication).

- Symptomatic coronary artery disease requiring an intervention within 3 months prior
to or during Screening or anticipated during the fixed duration part of the study

- Decompensated cardiac failure if not under close supervision

- Known and documented life-threatening cardiac arrhythmias

- Acute myocardial infarction within 6 months prior to, or during Screening

- Cerebrovascular events (including transient ischemic attack) within 3 months prior
to, or during Screening

- Known or suspicion of pulmonary veno-occlusive disease (PVOD)

- Administration of ERAs, intravenous prostacyclins / prostacyclin analogs, or
investigational treatment within 90 days prior to Randomization

- Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral,
inhaled or subcutaneous (SC) prostacyclins / prostacyclin analogues, prostacyclin
receptor agonists or riociguat, a) within 90 days prior to Randomization, or b)
anticipated during the fixed duration part of the double-blind [DB] period

- Hypotension, that is, systolic blood pressure (SBP) less than (<) 90 millimeters of
mercury (mmHg) or diastolic blood pressure (DBP) <50 mmHg at Screening.

- Severe renal dysfunction with an estimated Glomerular Filtration Rate <30
milliliters per minute per 1.73 meter square (mL/min/1.73 m^2) using the Chronic
Kidney Disease Epidemiology Collaboration formula at Screening

- Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C,
based on records that confirm documented medical history

- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater
than or equal to (>=) 1.5*upper limit of normal (ULN) at Screening

- Hemoglobin <100 g/L (<10 gram per deciliter [g/dL]) at Screening


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Thromboembolic Pulmonary Hypertension

Intervention(s)

Drug: Placebo

Drug: Macitentan

Primary Outcome(s)

Change From Baseline to Week 28 in 6- minute Walk Distance [6MWD] [Time Frame: Baseline up to Week 28]

Secondary Outcome(s)

Change from Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score [Time Frame: Baseline up to Week 28]

Time to Clinical Worsening up to End-of double-blind-treatment (EODBT) Period [Time Frame: Up to EODBT (variable duration per participant, up to 3.5 years)]

Change from baseline to Week 28 in Euro Quality of life-5-Dimension-5-Level (EQ-5D-5L) Utility Score [Time Frame: Baseline up to Week 28]

Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms Based on (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score [Time Frame: Baseline up to Week 28]

Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity [Time Frame: Baseline up to Week 28]

Number of Participants with Improvement in WHO Functional Class (WHO FC) From Baseline to Week 28 [Time Frame: Baseline up to Week 28]

Secondary ID(s)

67896062CTP3001

CR108742

2019-004131-24

Source(s) of Monetary Support

Please refer to primary and secondary sponsors