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A Clinical Study to Find Out if Macitentan is Effective and Safe in Japanese Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Primary Purpose

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Status
Terminated
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
macitentan 10 mg
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Thromboembolic Pulmonary Hypertension (CTEPH) focused on measuring CTEPH, chronic thromboembolic pulmonary hypertension, macitentan

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fukuoka University Nishijin Hospital
  • Fukushima Medical University Hospital
  • Kagoshima University Hospital
  • Nara Medical University Hospital
  • Kokura Kinen Hospital
  • Kobe University Hospital
  • Saitama Cardiovascular and Respiratory Center
  • Kure Kyosai Hospital
  • Kurume University Hospital
  • Toho University Ohashi Medical Center
  • IIUHW Mita Hospital
  • Kyorin University Hospital
  • Nagasaki University Hospital
  • National Hospital Organization Okayama Medical Center
  • Sapporo Medical University Hospital
  • Hokkaido University Hospital
  • Sasebo City General Hospital
  • Keio University Hospital
  • National Cerebral and Cardiovascular Center Hospital
  • University of Tsukuba Hospital
  • Mie University Hospital
  • Yamagata University Hospital
  • Yokohama City University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open-label treatment period

Arm Description

oral administration of macitentan 10 mg once daily

Outcomes

Primary Outcome Measures

Evaluate the ratio in pulmonary vascular resistance (PVR) at rest from baseline to Week 16
The resistance in the artery carrying blood to the lungs is called PVR. The PVR is the resistance in the artery carrying blood to the lungs and that has to be overcome by the right ventricle in heart in order to let blood flow to the lungs occur. The ratio in PVR at rest indicates the efficacy of macitentan in patients with CTEPH. The ratio in PVR at rest is calculated as PVR at Week 16 divided by baseline PVR. The ratio in PVR at rest from baseline to Week 16 of administration of macitentan is evaluated in subjects with CTEPH who are not indicated for pulmonary endarterectomy (PEA) and/or subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after PEA and/or balloon pulmonary angioplasty (BPA).

Secondary Outcome Measures

Change from baseline to Week 16 in PVR at rest
The PVR at rest will be calculated to evaluate the change in PVR at rest from pre-dosing (baseline) to post-dosing (Week 16).
Change from baseline to Week 16 in pulmonary vascular resistance index (PVRI) at rest
The indexed PVR (PVRI) at rest will be calculated to evaluate the change in PVRI at rest from pre-dosing (baseline) to post-dosing (Week 16).
Change from baseline to Week 24 in 6-minute walk distance (6MWD)
The purpose of the 6-minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. This endpoint evaluates the change in 6MWD from pre-dosing (baseline) to post-dosing (Week 24).
Change from baseline to Week 24 in Borg dyspnea index
The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement. This endpoint evaluates the change in the Borg dyspnea index assessed at the end of measuring the 6MWD from pre-dosing (baseline) to post-dosing (Week 24).
Change from baseline to Week 24 in WHO functional class (WHO FC)
This endpoint evaluates the change of WHO functional class from pre-dosing (baseline) to post-dosing (Week 24). 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 a flight of stairs, grocery shopping, or making the bed). 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 (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.

Full Information

First Posted
January 10, 2019
Last Updated
June 16, 2021
Sponsor
Actelion
Collaborators
EPS Corporation, Imepro Inc., General Laboratory, BML, Inc., Mitsubishi Logistics Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03809650
Brief Title
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

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Due to a change in the development strategy
Study Start Date
January 8, 2019 (Actual)
Primary Completion Date
June 29, 2020 (Actual)
Study Completion Date
June 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
Collaborators
EPS Corporation, Imepro Inc., General Laboratory, BML, Inc., Mitsubishi Logistics Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Keywords
CTEPH, chronic thromboembolic pulmonary hypertension, macitentan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-label treatment period
Arm Type
Experimental
Arm Description
oral administration of macitentan 10 mg once daily
Intervention Type
Drug
Intervention Name(s)
macitentan 10 mg
Other Intervention Name(s)
ACT-064992, Opsumit®
Intervention Description
macitentan 10 mg, film-coated tablet, oral use
Primary Outcome Measure Information:
Title
Evaluate the ratio in pulmonary vascular resistance (PVR) at rest from baseline to Week 16
Description
The resistance in the artery carrying blood to the lungs is called PVR. The PVR is the resistance in the artery carrying blood to the lungs and that has to be overcome by the right ventricle in heart in order to let blood flow to the lungs occur. The ratio in PVR at rest indicates the efficacy of macitentan in patients with CTEPH. The ratio in PVR at rest is calculated as PVR at Week 16 divided by baseline PVR. The ratio in PVR at rest from baseline to Week 16 of administration of macitentan is evaluated in subjects with CTEPH who are not indicated for pulmonary endarterectomy (PEA) and/or subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after PEA and/or balloon pulmonary angioplasty (BPA).
Time Frame
From Baseline to Week 16
Secondary Outcome Measure Information:
Title
Change from baseline to Week 16 in PVR at rest
Description
The PVR at rest will be calculated to evaluate the change in PVR at rest from pre-dosing (baseline) to post-dosing (Week 16).
Time Frame
From baseline to Week 16
Title
Change from baseline to Week 16 in pulmonary vascular resistance index (PVRI) at rest
Description
The indexed PVR (PVRI) at rest will be calculated to evaluate the change in PVRI at rest from pre-dosing (baseline) to post-dosing (Week 16).
Time Frame
From baseline to Week 16
Title
Change from baseline to Week 24 in 6-minute walk distance (6MWD)
Description
The purpose of the 6-minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. This endpoint evaluates the change in 6MWD from pre-dosing (baseline) to post-dosing (Week 24).
Time Frame
From baseline to Week 24
Title
Change from baseline to Week 24 in Borg dyspnea index
Description
The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement. This endpoint evaluates the change in the Borg dyspnea index assessed at the end of measuring the 6MWD from pre-dosing (baseline) to post-dosing (Week 24).
Time Frame
From baseline to Week 24
Title
Change from baseline to Week 24 in WHO functional class (WHO FC)
Description
This endpoint evaluates the change of WHO functional class from pre-dosing (baseline) to post-dosing (Week 24). 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 a flight of stairs, grocery shopping, or making the bed). 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 (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.
Time Frame
From baseline to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
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: 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. 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: Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg 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) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yoshinari Yokoyama, PhD
Organizational Affiliation
Actelion Japan
Official's Role
Study Director
Facility Information:
Facility Name
Fukuoka University Nishijin Hospital
City
Fukuoka
ZIP/Postal Code
814-8522
Country
Japan
Facility Name
Fukushima Medical University Hospital
City
Fukushima
ZIP/Postal Code
960-1247
Country
Japan
Facility Name
Kagoshima University Hospital
City
Kagoshima
ZIP/Postal Code
890-8520
Country
Japan
Facility Name
Nara Medical University Hospital
City
Kashihara
ZIP/Postal Code
634-8522
Country
Japan
Facility Name
Kokura Kinen Hospital
City
Kitakyushu
ZIP/Postal Code
802-8555
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Saitama Cardiovascular and Respiratory Center
City
Kumagaya
ZIP/Postal Code
360-0197
Country
Japan
Facility Name
Kure Kyosai Hospital
City
Kure
ZIP/Postal Code
737-8505
Country
Japan
Facility Name
Kurume University Hospital
City
Kurume
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
Toho University Ohashi Medical Center
City
Meguro-ku
ZIP/Postal Code
153-8515
Country
Japan
Facility Name
IIUHW Mita Hospital
City
Minato-ku
ZIP/Postal Code
108-8329
Country
Japan
Facility Name
Kyorin University Hospital
City
Mitaka
ZIP/Postal Code
181-8611
Country
Japan
Facility Name
Nagasaki University Hospital
City
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Facility Name
National Hospital Organization Okayama Medical Center
City
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Facility Name
Sapporo Medical University Hospital
City
Sapporo
ZIP/Postal Code
060-8543
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Sasebo City General Hospital
City
Sasebo
ZIP/Postal Code
857-8511
Country
Japan
Facility Name
Keio University Hospital
City
Shinjuku-ku
ZIP/Postal Code
160-0016
Country
Japan
Facility Name
National Cerebral and Cardiovascular Center Hospital
City
Suita
ZIP/Postal Code
565-8565
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Mie University Hospital
City
Tsu
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Yamagata University Hospital
City
Yamagata
ZIP/Postal Code
990-0828
Country
Japan
Facility Name
Yokohama City University Hospital
City
Yokohama
ZIP/Postal Code
236-0004
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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 Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=AC-055E301&amp;attachmentIdentifier=aa227840-255d-4f06-8064-e8ebb89a846a&amp;fileName=AC-055E301_CSR_Synopsis.pdf&amp;versionIdentifier=
Description
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)

Learn more about this trial

A Clinical Study to Find Out if Macitentan is Effective and Safe in Japanese Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

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