The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04271475




Registration number
NCT04271475
Ethics application status
Date submitted
13/02/2020
Date registered
17/02/2020

Titles & IDs
Public title
A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension
Scientific title
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
Secondary ID [1] 0 0
2019-004131-24
Secondary ID [2] 0 0
CR108742
Universal Trial Number (UTN)
Trial acronym
MACiTEPH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Thromboembolic Pulmonary Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Macitentan
Treatment: Drugs - Placebo

Experimental: Macitentan - Participant will receive macitentan at a dose of 10 milligram (mg) once daily (OD) for 4 weeks, followed by a dose of macitentan 37.5 mg for another 4 weeks and continue with the target dose of macitentan 75 mg. Participants who have reached the target dose of 75 mg, completed the Double-blind (DB) period up to Week 28 (either on treatment or in Post-treatment observation period \[PTOP\]) at minimum, may be eligible for transitioning into the Open label (OL) extension period once all participants have completed the DB part of the study, or earlier if they experienced a Clinical event committee (CEC) confirmed clinical worsening event.

Experimental: Placebo - Participants will receive placebo tablets matching the macitentan 10 mg, macitentan 37.5mg and macitentan 75 mg tablets, respectively. Participants who completed the DB period as per protocol either on treatment or in PTOP are eligible for transitioning to the OL extension period and will receive macitentan 75 mg after an 8-week double-dummy uptitration (macitentan 10 mg for 4 weeks, followed by 37.5 mg for another 4 weeks).


Treatment: Drugs: Macitentan
Participants will receive Macitentan film-coated tablets orally od.

Treatment: Drugs: Placebo
Participant will receive matching placebo tablets orally od.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 28 in 6- minute Walk Distance [6MWD]
Timepoint [1] 0 0
Baseline up to Week 28
Secondary outcome [1] 0 0
Time to Clinical Worsening up to End-of double-blind-treatment (EODBT) Period
Timepoint [1] 0 0
Up to EODBT (variable duration per participant, up to 3.5 years)
Secondary outcome [2] 0 0
Number of Participants with Improvement in WHO Functional Class (WHO FC) From Baseline to Week 28
Timepoint [2] 0 0
Baseline up to Week 28
Secondary outcome [3] 0 0
Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms Based on (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score
Timepoint [3] 0 0
Baseline up to Week 28
Secondary outcome [4] 0 0
Change from Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score
Timepoint [4] 0 0
Baseline up to Week 28
Secondary outcome [5] 0 0
Change from baseline to Week 28 in Euro Quality of life-5-Dimension-5-Level (EQ-5D-5L) Utility Score
Timepoint [5] 0 0
Baseline up to Week 28
Secondary outcome [6] 0 0
Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity
Timepoint [6] 0 0
Baseline up to Week 28

Eligibility
Key inclusion criteria
* Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization [WHO] Group 4) fulfilling one of the following criteria: a) inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA), and deemed inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue pulmonary endarterectomy (PEA)
* 6-minute walk distance (6MWD) greater than or equal to (>=) 100 meter (m) and less than or equal to (<=) 450 meters (m), documented by an eligibility and a baseline 6-minute walk test (6MWT). The baseline 6MWD must not differ by more than 15 percent (%) from the eligibility test
* World Health Organization functional class (WHO FC) >= II
* Participants are to receive riociguat as per local standard of care, unless it is contraindicated or unavailable
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Acute pulmonary embolism within 3 months prior to or during Screening
* Planned balloon pulmonary angioplasty (BPA) during the fixed duration part of the double-blind period
* Significant obstructive and restrictive lung disease
* Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (for example, intermittent claudication).
* Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the fixed duration part of the study
* Decompensated cardiac failure if not under close supervision
* Known and documented life-threatening cardiac arrhythmias
* Acute myocardial infarction within 6 months prior to, or during Screening
* Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening
* Known or suspicion of pulmonary veno-occlusive disease (PVOD)
* Administration of ERAs, intravenous prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization
* Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral, inhaled or subcutaneous (SC) prostacyclins / prostacyclin analogues, prostacyclin receptor agonists or riociguat, a) within 90 days prior to Randomization, or b) anticipated during the fixed duration part of the double-blind [DB] period
* Hypotension, that is, systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) <50 mmHg at Screening.
* Severe renal dysfunction with an estimated Glomerular Filtration Rate <30 milliliters per minute per 1.73 meter square (mL/min/1.73 m^2) using the Chronic Kidney Disease Epidemiology Collaboration formula at Screening
* Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history
* Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than or equal to (>=) 1.5*upper limit of normal (ULN) at Screening
* Hemoglobin <100 g/L (<10 gram per deciliter [g/dL]) at Screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Queensland Lung Transplant Service - Chermside
Recruitment hospital [2] 0 0
St Vincent's hospital - Darlinghurst
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New Mexico
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Argentina
State/province [21] 0 0
Buenos Aires
Country [22] 0 0
Argentina
State/province [22] 0 0
C.a.b.a.
Country [23] 0 0
Argentina
State/province [23] 0 0
Ciudad Autonoma de Buenos Aires
Country [24] 0 0
Austria
State/province [24] 0 0
Graz
Country [25] 0 0
Austria
State/province [25] 0 0
Linz
Country [26] 0 0
Austria
State/province [26] 0 0
Vienna
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Sofia
Country [28] 0 0
Canada
State/province [28] 0 0
Alberta
Country [29] 0 0
Canada
State/province [29] 0 0
Ontario
Country [30] 0 0
China
State/province [30] 0 0
Beijing
Country [31] 0 0
China
State/province [31] 0 0
Chongqing
Country [32] 0 0
China
State/province [32] 0 0
Guangzhou
Country [33] 0 0
China
State/province [33] 0 0
Hangzhou
Country [34] 0 0
China
State/province [34] 0 0
Nanjing
Country [35] 0 0
China
State/province [35] 0 0
Qingdao
Country [36] 0 0
China
State/province [36] 0 0
Shanghai
Country [37] 0 0
China
State/province [37] 0 0
Shenyang
Country [38] 0 0
China
State/province [38] 0 0
Tian Jin
Country [39] 0 0
China
State/province [39] 0 0
Xi'An
Country [40] 0 0
Colombia
State/province [40] 0 0
Bogota
Country [41] 0 0
Colombia
State/province [41] 0 0
Cali
Country [42] 0 0
Colombia
State/province [42] 0 0
Medellin
Country [43] 0 0
Czechia
State/province [43] 0 0
Praha 2
Country [44] 0 0
Denmark
State/province [44] 0 0
Aarhus N
Country [45] 0 0
France
State/province [45] 0 0
Brest
Country [46] 0 0
France
State/province [46] 0 0
Grenoble Cedex 9
Country [47] 0 0
France
State/province [47] 0 0
Le Kremlin-Bicetre Cedex
Country [48] 0 0
France
State/province [48] 0 0
Lille Cedex
Country [49] 0 0
France
State/province [49] 0 0
Montpellier
Country [50] 0 0
France
State/province [50] 0 0
St Priest en Jarez Cedex
Country [51] 0 0
France
State/province [51] 0 0
Toulouse Cedex 9
Country [52] 0 0
France
State/province [52] 0 0
Vandoeuvre les Nancy Cedex
Country [53] 0 0
Germany
State/province [53] 0 0
Bonn
Country [54] 0 0
Germany
State/province [54] 0 0
Dresden
Country [55] 0 0
Germany
State/province [55] 0 0
Giessen
Country [56] 0 0
Germany
State/province [56] 0 0
Hamburg
Country [57] 0 0
Germany
State/province [57] 0 0
Hannover
Country [58] 0 0
Germany
State/province [58] 0 0
Heidelberg
Country [59] 0 0
Germany
State/province [59] 0 0
Homburg
Country [60] 0 0
Germany
State/province [60] 0 0
Jena
Country [61] 0 0
Germany
State/province [61] 0 0
München
Country [62] 0 0
Hungary
State/province [62] 0 0
Budapest
Country [63] 0 0
Hungary
State/province [63] 0 0
Szeged
Country [64] 0 0
Israel
State/province [64] 0 0
Tel Aviv
Country [65] 0 0
Israel
State/province [65] 0 0
Tel-Hashomer
Country [66] 0 0
Italy
State/province [66] 0 0
Chieti
Country [67] 0 0
Italy
State/province [67] 0 0
Pavia
Country [68] 0 0
Italy
State/province [68] 0 0
Pisa
Country [69] 0 0
Italy
State/province [69] 0 0
Roma
Country [70] 0 0
Italy
State/province [70] 0 0
Torino
Country [71] 0 0
Japan
State/province [71] 0 0
Bunkyo
Country [72] 0 0
Japan
State/province [72] 0 0
Fukuoka
Country [73] 0 0
Japan
State/province [73] 0 0
Hiroshima
Country [74] 0 0
Japan
State/province [74] 0 0
Kanagawa
Country [75] 0 0
Japan
State/province [75] 0 0
Kobe
Country [76] 0 0
Japan
State/province [76] 0 0
Kyoto
Country [77] 0 0
Japan
State/province [77] 0 0
Matsumoto
Country [78] 0 0
Japan
State/province [78] 0 0
Meguro-ku
Country [79] 0 0
Japan
State/province [79] 0 0
Mitaka
Country [80] 0 0
Japan
State/province [80] 0 0
Nagoya
Country [81] 0 0
Japan
State/province [81] 0 0
Okayama
Country [82] 0 0
Japan
State/province [82] 0 0
Sapporo-shi
Country [83] 0 0
Japan
State/province [83] 0 0
Suita-Shi
Country [84] 0 0
Japan
State/province [84] 0 0
Tokyo
Country [85] 0 0
Japan
State/province [85] 0 0
Tsukuba-City
Country [86] 0 0
Korea, Republic of
State/province [86] 0 0
Busan
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Seoul
Country [88] 0 0
Lithuania
State/province [88] 0 0
Kaunas
Country [89] 0 0
Lithuania
State/province [89] 0 0
Vilnius
Country [90] 0 0
Mexico
State/province [90] 0 0
Ciudad De México
Country [91] 0 0
Mexico
State/province [91] 0 0
Mexico
Country [92] 0 0
Mexico
State/province [92] 0 0
Monterrey
Country [93] 0 0
Mexico
State/province [93] 0 0
Morelia
Country [94] 0 0
Mexico
State/province [94] 0 0
Nuevo Leon
Country [95] 0 0
Poland
State/province [95] 0 0
Kraków
Country [96] 0 0
Poland
State/province [96] 0 0
Lublin
Country [97] 0 0
Poland
State/province [97] 0 0
Otwock
Country [98] 0 0
Portugal
State/province [98] 0 0
Almada
Country [99] 0 0
Romania
State/province [99] 0 0
Bucuresti
Country [100] 0 0
Romania
State/province [100] 0 0
Tg. Mures
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Kazan
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Moscow
Country [103] 0 0
Russian Federation
State/province [103] 0 0
Saint-Petersburg
Country [104] 0 0
Russian Federation
State/province [104] 0 0
Volgograd
Country [105] 0 0
Saudi Arabia
State/province [105] 0 0
Riyadh
Country [106] 0 0
Serbia
State/province [106] 0 0
Belgrade
Country [107] 0 0
Serbia
State/province [107] 0 0
Sremska Kamenica
Country [108] 0 0
Singapore
State/province [108] 0 0
Singapore
Country [109] 0 0
Slovakia
State/province [109] 0 0
Bratislava
Country [110] 0 0
Spain
State/province [110] 0 0
Barcelona
Country [111] 0 0
Spain
State/province [111] 0 0
Madrid
Country [112] 0 0
Spain
State/province [112] 0 0
Málaga
Country [113] 0 0
Spain
State/province [113] 0 0
Toledo
Country [114] 0 0
Taiwan
State/province [114] 0 0
Kaohsiung
Country [115] 0 0
Taiwan
State/province [115] 0 0
Taipei
Country [116] 0 0
Taiwan
State/province [116] 0 0
Taoyuan
Country [117] 0 0
Thailand
State/province [117] 0 0
Chiang Mai
Country [118] 0 0
Thailand
State/province [118] 0 0
Khon Kaen
Country [119] 0 0
Thailand
State/province [119] 0 0
Pathumthani
Country [120] 0 0
Turkey
State/province [120] 0 0
Adana
Country [121] 0 0
Turkey
State/province [121] 0 0
Ankara
Country [122] 0 0
Turkey
State/province [122] 0 0
Denizli
Country [123] 0 0
Turkey
State/province [123] 0 0
Eskisehir
Country [124] 0 0
Turkey
State/province [124] 0 0
Istanbul
Country [125] 0 0
Turkey
State/province [125] 0 0
Izmir
Country [126] 0 0
Turkey
State/province [126] 0 0
Kartal Istanbul
Country [127] 0 0
Turkey
State/province [127] 0 0
Mersin
Country [128] 0 0
Ukraine
State/province [128] 0 0
Cherkasy
Country [129] 0 0
Ukraine
State/province [129] 0 0
Dnipro
Country [130] 0 0
Ukraine
State/province [130] 0 0
Kyiv
Country [131] 0 0
Ukraine
State/province [131] 0 0
Lviv
Country [132] 0 0
Ukraine
State/province [132] 0 0
Ternopil
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Cambridge
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Glasgow
Country [135] 0 0
United Kingdom
State/province [135] 0 0
London
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Newcastle Upon Tyne
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Actelion Clinical Trial
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.