NCT04271475

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

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

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 127 (actual)
• Sponsor: Actelion · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).

Detailed description

CTEPH is one of the leading causes of severe pulmonary hypertension (PH), classified within World Health Organization (WHO) group 4 PH. It is a rare, progressive pulmonary vascular disease that if left untreated, leads to progressively increasing pulmonary vascular resistance (PVR) and eventually right ventricle failure and death. Histopathologic findings including endothelial cell dysfunction and distal pulmonary arterial remodeling are shared between PAH and CTEPH, and PH-specific therapies (that is, riociguat) have shown efficacy in inoperable and persistent/recurrent CTEPH. The endothelin receptor antagonist macitentan offers a different mode of action and addresses an important unmet medical need for an alternative treatment option in this indication. This study will assess the effect of macitentan 75 mg on exercise capacity in CTEPH. The total duration of the study is approximately 6 years. The study comprises of a screening period (at least 14 days and up to 60 days), a double-blind (DB) treatment period (28 weeks \[minimum duration\] up to 3.5 years), an open-label (OL) extension period (starts at end-of-DB-treatment \[EODBT\] and will end for all participants 104 weeks after the last participant has completed DB Week 28). The DB period consists of an 8-week up-titration phase and a maintenance phase. The maintenance phase is divided into a 28-week fixed duration part, at the end of which primary endpoint is assessed, and a variable duration part. The duration of the DB period for an individual participant depends on the timepoint of entry into the study and whether a CEC-confirmed clinical worsening event occurred. Participants who discontinue DB study intervention during the 28-week fixed duration part will be followed until Week 28 in a post-treatment observation period (PTOP).

Conditions

• Chronic Thromboembolic Pulmonary Hypertension

Interventions

Type	Name	Description
DRUG	Macitentan	Participants will receive Macitentan film-coated tablets orally od.
DRUG	Placebo	Participant will receive matching placebo tablets orally od.

Timeline

• Start date: 2020-07-07
• Primary completion: 2023-12-21
• Completion: 2023-12-21
• First posted: 2020-02-17
• Last updated: 2025-06-27
• Results posted: 2025-04-22

Locations

168 sites across 33 countries: United States, Argentina, Australia, Austria, Bulgaria, Canada, China, Colombia, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Lithuania, Mexico, Poland, Portugal, Romania, Russia, Saudi Arabia, Serbia, Singapore, Slovakia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study