Clinical Study to Assess the Long-term Safety, Tolerability, and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome (MAESTRO-OL)

Long Term, Single-arm, Open-label Extension Study of Protocol AC-055-305 to Assess the Safety, Tolerability and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of Eisenmenger syndrome.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Macitentan 10 mg tablet, once daily.

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A-1090
    • Gen Hosp Univ Vienna Dept Cardiology
• Bulgaria
  • Sofia, Bulgaria, 1309
    • Mhat Nat Card Hosp - Cardiology Clinic
  • Sofia, Bulgaria, 1309
    • Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept
  • Sofia, Bulgaria, 1750
    • Mhat Sveta Anna Clin Card
• Chile
  • Santiago, Chile, 7650018
    • Clinica Tabancura - Cardio Unit
  • Santiago RCH
    • Providencia, Santiago RCH, Chile, 7500691
      • Instituto Nacional del tórax
• China
  • Beijing, China, 100029
    • Beijing Anzhen Hospital, Cardiology Dpt
  • Beijing, China, 100037
    • Cardiovascular Institute&Fuwai Hospital
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital, Cardiology Dpt
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wu Han Asia Heart Hosp
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • The General Hosp of Shenyang Military Region
• France
  • Marseille Cedex 5, France, 13385
    • Hosp La Timone - Dept Pediatric Cardiology
  • Nantes Cedex 1, France, 44093
    • Hosp Laennec - Dept Cardiology
  • Paris cedex 15, France, 75908
    • Hosp Pompidou - Dept Congenital Cardiac Diseases
  • Pessac, France, 33604
    • Hosp Cardiology Haut Leveque - Dept Congenital Diseases
• Germany
  • Berlin, Germany, 13353
    • Herzzentrum Berlin, Ped Cardiology
  • Giessen, Germany, 35392
    • Universitätsklinikum Giessen - Pediatric Heart Center
  • Heidelberg, Germany, D-69120
    • Uni Heidelberg - Kinderkardiologie
• Greece
  • Thessaloniki, Greece, 54636
    • Ahepa University General hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cardiologia (INC) Ignacio Chavez
  • Querétaro, Mexico
    • Instituto de Corazón de Querétaro
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64718
      • Unidad de Investigacion Clin En Med, Sc (Udicem)
• Philippines
  • Manila, Philippines
    • PHC, MAB
• Poland
  • Gdańsk, Poland, 80-952
    • Cardiology Gdańsk Univ
  • Krakow, Poland, 31-202
    • Cardiology Kraków Univ
  • Wrocław, Poland, 51-124
    • Cardiology Wrocław
• Portugal
  • Coimbra, Portugal, 3000-075
    • Hosp Univ Coimbra - Dpt Cardiology
  • Lisboa, Portugal, 1169-024
    • Hosp Sta Marta - Dept Cardiology
• Romania
  • Bucaresti, Romania, 022328
    • Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii
  • Targu-Mures, Romania, 540136
    • Cardio Med SRL
  • Timisoara, Romania, 300312
    • Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • Sci Institute Systemic Poriblems Cardio Diseases Kemerovo
  • Moscow, Russian Federation, 121552
    • Russian Cardiology Scientific and Production Complex
  • St Petersburg, Russian Federation, 194156
    • V. A. Almazov Institute of Cardiology
• Serbia
  • Belgrade, Serbia, 11040
    • Dedinje Cardiovasc Inst - Cardiovasc Research Ctr
  • Belgrade, Serbia, 11080
    • Clin Hosp Ctr Zemun - Cardiology Dept
  • Belgrade, Serbia, 11070
    • Mother and Child Health Care Institute Dr. Vukan Cupic
• Spain
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult
  • Sevilla, Spain, 41007
    • Hosp Univ Virgen Macarena - Dpt Cardiology
  • Valencia, Spain, 46009
    • Hosp Universitario La Fe Dpt Cardiology
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Univ Hosp Congenital Heart Centre
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/The Emory Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hosp/Wash Univ School of Med
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Children's Heart Center Nevada
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Nationwide Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030-2303
      • Texas Children'S Hosp - Dept of Cardiology
• Vietnam
  • Hanoi, Vietnam
    • Hanoi Medical University Hospital
  • Ho Chi Minh, Vietnam
    • Children'S Hospital, Ho Chi Minh
  • Ho Chi Minh, Vietnam
    • Tam Duc Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects with ES (including those with Down Syndrome) having completed the double-blind AC-055-305 / MAESTRO study as scheduled, i.e., who remained in the double-blind study up to Week 16 (whether or not they were still taking study drug at the end of this period).

Exclusion Criteria:

Subjects who prematurely discontinue double-blind study drug during the AC-055-305 / MAESTRO study due to:

• an AE assessed as related to the use of study drug,
• or elevated liver tests (related or unrelated to study drug).

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 10 mg tablet, once daily.	Drug: Macitentan 10 mg tablet, once daily.; Macitentan 10 mg tablet, once daily.; Other Names: ACT-064992; Macitentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12	NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward.	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Change in WHO Functional Class (FC) at Month 6 and 12	Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward.	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Change in Borg Dyspnea Score at Month 6 and 12	The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward.	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12	No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT)	From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.

Collaborators and Investigators

• Sponsor: Actelion

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2013
• Primary Completion (Actual): January 12, 2018
• Study Completion (Actual): January 12, 2018

Study Registration Dates

• First Submitted: November 29, 2012
• First Submitted That Met QC Criteria: November 29, 2012
• First Posted (Estimate): December 3, 2012

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: exercise capacity; Eisenmenger Syndrome
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Hypertension, Pulmonary; Heart Defects, Congenital; Cardiovascular Abnormalities; Hypertension; Pulmonary Arterial Hypertension; Eisenmenger Complex; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055-308

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No