Clinical Study to Assess the Safety, Tolerability and Efficacy of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (MERIT-2)

MERIT-2 : Long Term, Multicenter, Single-arm, Open-label Extension Study of the MERIT-1 Study, to Assess the Safety, Tolerabilty and Efficacy of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH)

Study Overview

• Status: Completed
• Conditions: Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Drug: Macitentan

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
• China
  • Beijing, China
  • Guangzhou, China
  • Shanghai, China
  • Shenyang, China
  • Wuhan, China
• Czechia
  • Praha 2, Czechia
• France
  • Le Kremlin-Bicetre Cedex, France
  • Paris Cedex 15, France
  • Toulouse Cedex 9, France
• Germany
  • Giessen, Germany
  • Heidelberg, Germany
  • Würzburg, Germany
• Hungary
  • Budapest, Hungary
  • Debrecen, Hungary
• Lithuania
  • Kaunas, Lithuania
• Mexico
  • Ciudad de Mexico, Mexico
• Poland
  • Lublin, Poland
  • Wrocław, Poland
• Russian Federation
  • Kemerovo, Russian Federation
  • Moscow, Russian Federation
  • Novosibirsk, Russian Federation
  • St Petersburg, Russian Federation
  • Tomsk, Russian Federation
• Switzerland
  • Zürich, Switzerland
• Thailand
  • Bangkok, Thailand
  • Chiang Mai, Thailand
• Turkey
  • Capa_Istanbul, Turkey
• Ukraine
  • Kyiv, Ukraine
  • Lviv, Ukraine
• United Kingdom
  • Cambridge, United Kingdom
  • London, United Kingdom
  • Sheffield, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent
• Subject with CTEPH having completed the double-blind (DB) AC-055E201/ MERIT-1 study as scheduled (i.e., who remained in the DB study up to Week 24).
• Females of childbearing potential must have a negative pre-treatment serum pregnancy test, be advised on appropriate methods of contraception, and agree to use 2 reliable methods of contraception.

Exclusion Criteria:

• Permanent discontinuation of DB study treatment due to an hepatic adverse event or liver aminotransferase abnormalities.
• Any known factor (e.g., drug or substance abuse) or disease (e.g., unstable psychiatric illness) that, in the opinion of the investigator, may interfere with treatment compliance or interpretation of the results, or that may influence the ability to comply with any of the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Macitentan; Macitentan 10mg, oral tablet, once daily	Drug: Macitentan; Macitentan 10mg, oral tablet, once daily; Other Names: ACT-064992

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are those events that started after administration of the first dose and up to safety follow-up visit/end of study, that is, 30 days after the last dose of study medication.	Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Number of Participants With AEs Leading to Study Drug Discontinuation	Number of participants with AEs leading to study drug discontinuation was reported.	Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)	A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulting in any of following outcomes: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. Treatment-emergent SAEs were those events that started after administration of the first dose and up to safety follow-up visit/end of study, that is, 30 days after the last dose of study medication.	Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Number of Participants With Hemoglobin Abnormalities	Number of participants with hemoglobin abnormalities were reported. It included hemoglobin less than (<) 80 grams per liter (g/L), hemoglobin <100 g/L, hemoglobin greater than or equal to (>=) 80 g/L and <100 g/L, hemoglobin <100g/L and a decrease of >20 g/L from baseline, decrease of >20 g/L in hemoglobin from baseline, decrease of >20 g/L and <=50 g/L in hemoglobin from baseline, and decrease of >50 g/L in hemoglobin from baseline.	Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Number of Participants With Liver Tests Abnormalities	Number of participants with liver tests abnormalities were reported. It included alanine aminotransferase (ALT) or aspartate aminotransferase (AST): >=3 x Upper limit of the normal range (ULN), >=3 and <5 x ULN, >=5 ULN, and >=5 and <8 x ULN, >= 8 x ULN, and total bilirubin >=2 x ULN.	Up to 30 days after study treatment discontinuation (treatment exposure ranged from 1 to 82 months)
Change From Baseline in Blood Pressure at Month 6	Change from baseline in blood pressure at Month 6 (both systolic blood pressure [SBP] and diastolic blood pressure [DBP]) was reported.	Baseline and Month 6
Change From Baseline in Pulse Rate at Month 6	Change from baseline in pulse rate at Month 6 was reported.	Baseline and Month 6
Change From Baseline in Body Weight at Month 6	Change from baseline in body weight at Month 6 was reported.	Baseline and Month 6

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline to each scheduled time point inexercise capacity, as measured by the 6MWD	Baseline up to 30 months
Change from baseline to each scheduled time point in Borg dyspnea index	Baseline up to 30 months
Proportion of subjects with worsening of WHO FC from baseline to each scheduled time point.	Baseline up to 30 months
marked laboratory abnormalities during treatment period and up to 30 days after study drug discontinuation	From baseline up to 30 days after study drug discontinuation.
Change in vital signs (blood pressure , heart rate) and body weight from baseline to all assessed time points during the study	From baseline up to 30 days after study drug discontinuation.

Collaborators and Investigators

• Sponsor: Actelion

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2015
• Primary Completion (Actual): March 21, 2022
• Study Completion (Actual): March 21, 2022

Study Registration Dates

• First Submitted: January 2, 2014
• First Submitted That Met QC Criteria: February 11, 2014
• First Posted (Estimate): February 12, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Chronic thromboembolic pulmonary hypertension (CTEPH)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055E202; 2013-003457-25 (EudraCT Number)