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

NCT01739400 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: AC-055-308
• Study Type: interventional
• Target: 217
• Locations: 19 countries
• Sites: 51

Brief Summary

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

Conditions

Pulmonary Arterial Hypertension

Keywords

Eisenmenger Syndrome; exercise capacity

Outcome Measures

Primary Outcomes (4)

• 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.

Study Arms (1)

Macitentan

EXPERIMENTAL

Macitentan 10 mg tablet, once daily.

Drug: Macitentan 10 mg tablet, once daily.

Interventions

Macitentan 10 mg tablet, once daily. DRUG

Macitentan 10 mg tablet, once daily.

Also known as: Macitentan, ACT-064992

Macitentan

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Actelion: lead

Study Sites (51)

Emory University Hospital/the Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Barnes-Jewish Hosp/Wash Univ School of Med

St Louis, Missouri, 63110, United States

Location

Children'S Heart Center Nevada

Las Vegas, Nevada, 89109, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43210, United States

Location

Texas Children'S Hosp - Dept of Cardiology

Houston, Texas, 77030-2303, United States

Location

Gen Hosp Univ Vienna Dept Cardiology

Vienna, A-1090, Austria

Location

Mhat Nat Card Hosp - Cardiology Clinic

Sofia, 1309, Bulgaria

Location

Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept

Sofia, 1309, Bulgaria

Location

Mhat Sveta Anna Clin Card

Sofia, 1750, Bulgaria

Location

Instituto Nacional del Torax

Providencia, Santiago RCH, 7500691, Chile

Location

Clinica Tabancura - Cardio Unit

Santiago, 7650018, Chile

Location

Guangdong General Hospital, Cardiology Dpt

Guangzhou, Guangdong, 510080, China

Location

Wu Han Asia Heart Hosp

Wuhan, Hubei, 430022, China

Location

The General Hosp of Shenyang Military Region

Shenyang, Liaoning, 110016, China

Location

Beijing Anzhen Hospital, Cardiology Dpt

Beijing, 100029, China

Location

Cardiovascular Institute&Fuwai Hospital

Beijing, 100037, China

Location

Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation

Shanghai, 200433, China

Location

Hosp La Timone - Dept Pediatric Cardiology

Marseille, 13385, France

Location

Hosp Laennec - Dept Cardiology

Nantes, 44093, France

Location

Hosp Pompidou - Dept Congenital Cardiac Diseases

Paris, 75908, France

Location

Hosp Cardiology Haut Leveque - Dept Congenital Diseases

Pessac, 33604, France

Location

Herzzentrum Berlin, Ped Cardiology

Berlin, 13353, Germany

Location

Universitätsklinikum Giessen - Pediatric Heart Center

Giessen, 35392, Germany

Location

Uni Heidelberg - Kinderkardiologie

Heidelberg, D-69120, Germany

Location

Ahepa University General Hospital

Thessaloniki, 54636, Greece

Location

Institut Jantung Negara

Kuala Lumpur, 50400, Malaysia

Location

Unidad de Investigacion Clin En Med, Sc (Udicem)

Monterrey, Nuevo León, 64718, Mexico

Location

Instituto Nacional de Cardiologia (Inc) Ignacio Chavez

Mexico City, 14080, Mexico

Location

Instituto de Corazon de Querètaro

Querétaro, Mexico

Location

PHC, MAB

Manila, Philippines

Location

Cardiology Gdańsk Univ

Gdansk, 80-952, Poland

Location

Cardiology Kraków Univ

Krakow, 31-202, Poland

Location

Cardiology Wrocław

Wroclaw, 51-124, Poland

Location

Hosp Univ Coimbra - Dpt Cardiology

Coimbra, 3000-075, Portugal

Location

Hosp Sta Marta - Dept Cardiology

Lisbon, 1169-024, Portugal

Location

Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii

Bucaresti, 022328, Romania

Location

Cardio Med Srl

Târgu Mureş, 540136, Romania

Location

Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm

Timișoara, 300312, Romania

Location

Sci Institute Systemic Poriblems Cardio Diseases Kemerovo

Kemerovo, 650002, Russia

Location

Russian Cardiology Scientific and Production Complex

Moscow, 121552, Russia

Location

V. A. Almazov Institute of Cardiology

Saint Petersburg, 194156, Russia

Location

Dedinje Cardiovasc Inst - Cardiovasc Research Ctr

Belgrade, 11040, Serbia

Location

Mother and Child Health Care Institute Dr. Vukan Cupic

Belgrade, 11070, Serbia

Location

Clin Hosp Ctr Zemun - Cardiology Dept

Belgrade, 11080, Serbia

Location

Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult

Barcelona, 08035, Spain

Location

Hosp Univ Virgen Macarena - Dpt Cardiology

Seville, 41007, Spain

Location

Hosp Universitario La Fe Dpt Cardiology

Valencia, 46009, Spain

Location

Bristol Univ Hosp Congenital Heart Centre

Bristol, BS2 8BJ, United Kingdom

Location

Hanoi Medical University Hospital

Hanoi, Vietnam

Location

Children'S Hospital, Ho Chi Minh

Ho Chi Minh City, Vietnam

Location

Tam Duc Hospital

Ho Chi Minh City, Vietnam

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Eisenmenger Complex

Interventions

macitentan; Tablets

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

The MAESTRO parent study AC-055-305 (NCT01743001) did not meet its primary endpoint. The sponsor decided to prematurely terminate this OL study on January 12th 2018.

Results Point of Contact

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

clinical-trials-disclosure@its.jnj.com

+41 61 565 6565

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 3, 2012
• Study Start: September 10, 2013
• Primary Completion: January 12, 2018
• Study Completion: January 12, 2018
• Last Updated: April 16, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-03

Locations

PT (2); FR (4); PH (1); AU (1); CL (2); GR (1); SE (3); VN (3); RO (3); CN (6); RU (3); MY (1); GB (1); US (5); PL (3); DE (3); BU (3); ES (3); ME (3)