Clinical trial NCT03809650: A Clinical Study to Find Out if Macitentan is Effective and Safe in Japanese Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH).
Official title: A Prospective, Multicenter, Open-label, Single Arm, Phase III Study to Assess the Efficacy and Safety of Macitentan (ACT-064992) in Subjects With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Keywords: CTEPH
chronic thromboembolic pulmonary hypertension
macitentan
Lead sponsor: Actelion
Sponsor class: INDUSTRY
Collaborators: name: EPS Corporation
name: Imepro Inc.
name: General Laboratory, BML, Inc.
name: Mitsubishi Logistics Corporation
First posted: 2019-01-18
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The endothelin receptor antagonist macitentan showed significant improvement compared with placebo in pulmonary vascular resistance (PVR) and 6-minute walking distance (6MWD) in inoperable CTEPH patients in the phase II MERIT-1 trial (AC-055E201, NCT02021292). However, in the MERIT-1 trial Japanese patients were not included. Therefore, in line with Japan's medical environment, this phase III study is to confirm the efficacy and safety of macitentan in Japanese CTEPH patients.


Eligibility criteria: Inclusion Criteria:

* Written informed consent to participate in the study obtained from the subject or legal representative a) prior to initiation of any study mandated procedure
* Japanese subjects who have been diagnosed as having CTEPH:

  1. Subjects who have not undergone balloon pulmonary angioplasty (BPA) and for whom the investigator determines not to implement pulmonary endarterectomy (PEA) at the time of the acquisition of informed consent due to the organized thrombosis localized in the peripheral regions, high risk (complications, old age, etc.) or for any other reasons.
  2. Subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after undergoing pulmonary endarterectomy (PEA) and/or BPA.
* PH subjects whose WHO FC is I to IV
* 6MWD measured during the screening period ranges from 150 m to 450 m
* Subjects who meet the following conditions according to the right heart catheterization (RHC) performed during the screening period or within 8 weeks before the acquisition of the informed consent:

  1. Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg
  2. Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg (if PAWP cannot be measured or the value of PAWP is not reliable, left ventricular end-diastolic pressure ≤ 13 mmHg)
  3. Resting PVR ≥ 400 dyn\*sec/cm5
* Subjects treated with anti-coagulation agents, unfractionated heparin or low molecular weight heparin at least 90 days prior to RHC at baseline
* Women with childbearing potential with negative serum pregnancy test results and able to follow the appropriate contraceptive methods from the date of starting the study drug administration up to 30 days after the discontinuation or completion of the study drug administration. Fertile male subjects able to use condom during the same period.

Exclusion Criteria:

* BPA within 90 days prior to undergoing baseline RHC
* PEA within 180 days prior to undergoing baseline RHC
* Subjects with unstable pulmonary hemodynamics who have postoperative persistent or recurrent PH after undergoing PEA and/or BPA
* Recurrent thromboembolism undergoing treatment with oral anti-coagulation agents
* Symptomatic acute pulmonary embolism within 180 days prior to the start of study drug administration
* Known moderate-to-severe restrictive lung disease or obstructive lung disease or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema)
* Acute myocardial infarction during Screening period
* Severe liver impairment.
* Systolic blood pressure (SBP) \< 90 mmHg at screening.
* Any known factor or disease that may interfere with treatment compliance or full participation in the study

Primary outcomes:
measure: Evaluate the ratio in pulmonary vascular resistance (PVR) at rest from baseline to Week 16
timeFrame: From Baseline to Week 16
Secondary outcomes:
measure: Change from baseline to Week 16 in PVR at rest
timeFrame: From baseline to Week 16
measure: Change from baseline to Week 16 in pulmonary vascular resistance index (PVRI) at rest
timeFrame: From baseline to Week 16
measure: Change from baseline to Week 24 in 6-minute walk distance (6MWD)
timeFrame: From baseline to Week 24
measure: Change from baseline to Week 24 in Borg dyspnea index
timeFrame: From baseline to Week 24
measure: Change from baseline to Week 24 in WHO functional class (WHO FC)
timeFrame: From baseline to Week 24
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Fukuoka University Nishijin Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Kitakyushu
country: Japan
facility: Kokura Kinen Hospital
city: Kobe
country: Japan
facility: Kobe University Hospital
city: Kumagaya
country: Japan
facility: Saitama Cardiovascular and Respiratory Center
city: Kure
country: Japan
facility: Kure Kyosai Hospital
city: Kurume
country: Japan
facility: Kurume University Hospital
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center
city: Minato-ku
country: Japan
facility: IIUHW Mita Hospital
city: Mitaka
country: Japan
facility: Kyorin University Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Sasebo
country: Japan
facility: Sasebo City General Hospital
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center Hospital
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
city: Tsu
country: Japan
facility: Mie University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
Study officials:
affiliation: Actelion Japan
name: Yoshinari Yokoyama, PhD
role: STUDY_DIRECTOR
References: