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

NCT02021292 | Completed Phase 2 Results

• 1 other identifier: AC-055E201
• Study Type: interventional
• Target: 80
• Locations: 16 countries
• Sites: 36

Brief Summary

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

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Keywords

Chronic thromboembolic pulmonary hypertension (CTEPH)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest.

  The primary efficacy endpoint is defined as the PVR at rest at Week 16 expressed as percent of baseline PVR at rest.

  From baseline to Week 16

Secondary Outcomes (3)

• Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD).

  From baseline to Week 24

• Change From Baseline to Week 24 in Borg Dyspnea Index Collected at the End of the 6-minute Walk Test (6MWT).

  From baseline to Week 24

• Proportion of Subjects With Worsening in WHO Functional Class (FC) From Baseline to Week 24

  From baseline to Week 24

Study Arms (2)

Macitentan

EXPERIMENTAL

Macitentan 10 mg, oral tablet, to be taken once daily.

Drug: Macitentan

Placebo

PLACEBO COMPARATOR

Matching placebo oral tablet, to be taken once daily.

Drug: Placebo

Interventions

Macitentan DRUG

Macitentan 10 mg, oral tablet, to be taken once daily.

Also known as: ACT-064992

Macitentan

Placebo DRUG

Matching placebo oral tablet, to be taken once daily.

Placebo

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Subject with CTEPH (WHO Group 4) judged as inoperable due to the localization of the obstruction being surgically inaccessible (i.e., distal disease).
• Female 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.

You may not qualify if:

• Previous pulmonary endarterectomy.
• Recurrent thromboembolism despite sufficient oral anticoagulants.
• Symptomatic acute pulmonary embolism in the 6-month period prior to randomization.
• Known moderate-to-severe restrictive lung disease (i.e., TLC \< 60% of predicted value) or obstructive lung disease (i.e., FEV1 \< 70% of predicted, with FEV1/FVC \< 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
• Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements in the 3-month period prior to Screening visit or during the Screening period.

Sponsors & Collaborators

• Actelion: lead

Study Sites (36)

University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie

Leuven, 3000, Belgium

Location

Beijing Chao-Yang Hospital-Department of Respiration

Beijing, 100020, China

Location

Cardiovascular institute & Fuwai Hospital- Thrombus Center

Beijing, 100037, China

Location

The first affiliated hospital of guangzhou medical university-respiratory department

Guangzhou, 510120, China

Location

ngShanghai Pulmonary Hospital, Department of Pulmonary Circulation

Shanghai, 200433, China

Location

The General Hospital of Shenyang Military Region,Congenital Heart Disease Department

Shenyang, 110016, China

Location

Wuhan Asia Heart Hospital

Wuhan, 430022, China

Location

Centre for PPH, Charles University , II Interni klinika1.LF a VFN

Prague, 128 08, Czechia

Location

CHU de Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Européen Georges Pompidou Service de Pneumologie, soins intensifs et endoscopies bronchiques

Paris, 75908, France

Location

CHU de Toulouse Hopital Larrey

Toulouse, 31059, France

Location

Justus-Liebig-Universität Gießen

Giessen, 35392, Germany

Location

Thoraxklinik am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Missionsärztliche Klinik gGmbH Akademisches Lehrkrankenhaus der Julius-Maximilians-Universität

Würzburg, 97074, Germany

Location

Semmelweis Egyetem

Budapest, 1125, Hungary

Location

Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Kardiológiai Klinika

Debrecen, 4032, Hungary

Location

Lietuvos Sveikatos Mokslų Universiteto Ligoninės Kauno Klinikos Pulmonologijos-Imunologijos Klinika

Kaunas, 50161, Lithuania

Location

Instituto Nacional de Cardiologia (INC) Ignacio Chavez

Mexico City, 14080, Mexico

Location

Wojewódzki Szpital Specjalistyczny w Lublinie im. Stefana Kardynała Wyszyńskiego SPZOZ Oddział Kardiologii - Pododdział Intensywnego Nadzoru Kardiologicznego

Lublin, 20-718, Poland

Location

Wojewódzki Szpital Specjalistyczny we Wrocawiu

Wrocaw, 51-124, Poland

Location

Federal State Budgetary Institution "Scientific Research Institute of Systemic Problems of Cardiovascular Diseases", Siberian branch of RAMS

Kemerovo, 650002, Russia

Location

Federal State Budgetary Institution "Russian Cardiology Scientific and Production Complex" of the Ministry of Health Care of the Russian Federation

Moscow, 121552, Russia

Location

E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rosmedtechnology

Novosibirsk, 630055, Russia

Location

Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies"

Saint Petersburg, 197341, Russia

Location

Federal State Budgetary Institution "Research Institute for Cardiology" of Siberian Branch under the Russian Academy of Medical Sciences / Cardiovascular Surgery Department

Tomsk, 634012, Russia

Location

Severance Hospital, YonSei University Health System

Seoul, 3722, South Korea

Location

University Hospital Zürich

Zurich, 8091, Switzerland

Location

King Chulalongkorn Memorial Hospital, Division of Respiratory and Respiratory Critical Care Medicine

Bangkok, 10330, Thailand

Location

Siriraj Hospital, Division of Respiratory Disease and Tuberculosis

Bangkok, 10700, Thailand

Location

MAHARAJ NAKORN CHIANG MAI HOSPITAL, Department of Internal Medicine

Chiang Mai, 50200, Thailand

Location

Istanbul University İstanbul Faculty Medicine Pulmonology Department

Capa_Istanbul, 34093, Turkey (Türkiye)

Location

State Institute of Phthisiology and Pulmonology n.a. F.G. Yanovskiy of AMS Ukraine

Kyiv, 03680, Ukraine

Location

Lviv Regional Clinical Hospital, Cardiosurgery Department

Lviv, 79014, Ukraine

Location

Papworth Hospital NHS Trust, Pulmonary Vascular Diseases Unit

Cambridge, CB23 3RE, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Pulmonary Vascular Medicine

Sheffield, S10 2RX, United Kingdom

Location

Related Publications (3)

• Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11.

  PMID: 28919201 RESULT

• Kim NH, D'Armini AM, Howard LS, Jenkins DP, Jing ZC, Mayer E, Chamitava L, Lack G, Rofael H, Solonets M, Ghofrani HA. Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension. Pulm Ther. 2025 Mar;11(1):101-116. doi: 10.1007/s41030-024-00276-w. Epub 2024 Nov 9.

  PMID: 39520648 DERIVED

• Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2024 Apr;12(4):e21-e30. doi: 10.1016/S2213-2600(24)00027-4.

  PMID: 38548406 DERIVED

MeSH Terms

Interventions

macitentan

Results Point of Contact

• Title: Clinical Trial Disclosure Desk
• Organization: Actelion Pharmaceuticals Ltd.

clinical-trials-disclosure@actelion.com

Study Officials

• Kelly Papadakis, MD

  Actelion

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 27, 2013
• Study Start: August 20, 2014
• Primary Completion: September 28, 2016
• Study Completion: September 28, 2016
• Last Updated: March 30, 2025
• Results First Posted: January 23, 2018

Record last verified: 2025-03

Locations

CZ (1); FR (3); BE (1); KR (1); HU (2); DE (3); LI (1); CN (6); TU (1); PL (2); CH (1); TH (3); UA (2); ME (1); RU (5); GB (3)