A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension (MACiTEPH)
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|ClinicalTrials.gov Identifier: NCT04271475|
Recruitment Status : Recruiting
First Posted : February 17, 2020
Last Update Posted : February 17, 2021
|Condition or disease||Intervention/treatment||Phase|
|Chronic Thromboembolic Pulmonary Hypertension||Drug: Macitentan Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||144 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official 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|
|Actual Study Start Date :||July 7, 2020|
|Estimated Primary Completion Date :||May 14, 2024|
|Estimated Study Completion Date :||August 21, 2026|
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.
Participants will receive Macitentan film-coated tablets orally od.
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).
Participants will receive Macitentan film-coated tablets orally od.
Participant will receive matching placebo tablets orally od.
- Change From Baseline to Week 28 in 6- minute Walk Distance [6MWD] [ Time Frame: Baseline up to Week 28 ]Change from baseline to week 28 in 6MWD as measured by 6-minute walk test [6MWT]) will be reported. The purpose of the six-minute walk test (6MWT) is to quantify exercise tolerance and capacity. This standardized 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 6 minutes.
- Time to Clinical Worsening up to End-of double-blind-treatment (EODBT) Period [ Time Frame: Up to EODBT (variable duration per participant, up to 3.5 years) ]Time to first Clinical Event Committee (CEC) confirmed clinical worsening up to EODBT will be reported. Clinical worsening is defined as the occurrence of at least one of the following events: 1) All-cause death; 2) Heart and/or lung transplantation; 3) Unplanned pulmonary hypertension (PH)-related hospitalization; 4) PH-related deterioration from baseline identified by at least one of the following: a) Persistent increase in World Health Organization functional class (WHO FC) that cannot be explained by another cause (for example, viral infection); b) Persistent deterioration by at least 15 percent (%) in exercise capacity; as measured by the 6MWD; c) New or worsening signs or symptoms of right heart failure; 5) Rescue pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedure due to worsening of PH.
- Number of Participants with Improvement in WHO Functional Class (WHO FC) From Baseline to Week 28 [ Time Frame: Baseline up to Week 28 ]Improvement in WHO FC from baseline to Week 28 will be calculated for each participant. WHO FC test is used to assess disease severity. Four functional classes (FC) are defined from FC I (no limitation of physical activity) to FC IV (inability to carry out any physical activity without symptoms). Improvement is considered when a participant changes from a higher class to a lower class.
- Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms Based on (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score [ Time Frame: Baseline up to Week 28 ]The Cardiopulmonary Symptoms domain consists of 6 items (shortness of breath, fatigue, lack of energy, swelling in ankles or legs, swelling in stomach area and cough) reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT will be administered daily over a 7-day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items. Questionnaires to be completed at site at screening for training purpose. PAH-SYMPACT to be performed at home, during the 7-day period prior to the scheduled visit.
- Change from Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score [ Time Frame: Baseline up to Week 28 ]The Cardiovascular Symptoms domain consists of 5 items (heart palpitations [fluttering], rapid heartbeat, chest pain, chest tightness, and lightheadedness) reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT will be administered daily over a 7-day period. The recall period of symptom items is the last 24 hours. An average Cardiovascular Symptoms domain score is determined based on the daily scores of the 5 items. Questionnaires to be completed at site at screening for training purpose. PAH-SYMPACT to be performed at home, during the 7-day period prior to the scheduled visit.
- Change from baseline to Week 28 in Euro Quality of life-5-Dimension-5-Level (EQ-5D-5L) Utility Score [ Time Frame: Baseline up to Week 28 ]The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
- Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity [ Time Frame: Baseline up to Week 28 ]Change from baseline to week 28 in accelerometer-assessed proportion of time spent in moderate to vigorous physical activity will be assessed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04271475
|Contact: Study Contact||844-434-4210||JNJ.CT@sylogent.com|
|Study Director:||Actelion Clinical Trial||Actelion|