Clinical study assessing the safety and efficacy of macitentan in Fontan-palliated subjects.

Phase 1

• Conditions: Congenital Heart Failure; MedDRA version: 20.0Level: PTClassification code 10045545Term: Univentricular heartSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 21.1Level: PTClassification code 10065950Term: Cavopulmonary anastomosisSystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

• Registration Number: EUCTR2016-003320-23-GB
• Lead Sponsor: Actelion Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-08
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

- Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures
- Fontan-palliated subjects with either intra-atrial lateral tunnel total cavopulmonary connection (LT-TCPC), or extra cardiac tunnel TCPC (EC-TCPC) surgery > 1 year before Screening. Either LT- or EC-TCPC can be primary or secondary to atrio-pulmonary connection
- New York Heart Association (NYHA) functional class (FC) II or III (assessed by the investigator using the Specific Activity Scale
- Age range: >= 12 years old
- Women of childbearing potential must have a negative serum pregnancy test at the Randomization visit, perform monthly pregnancy tests, and use reliable contraception
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 94
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Pattern of Fontan circulation severity
- Deterioration of the Fontan-palliated condition
- Systolic BP < 90 mmHg (< 85 mmHg for < 18 years old and < 150 cm of height) at rest or during Cardiopulmonary exercise testing at screening or baseline
- Criteria related to macitentan use
- Limitations to Cardiopulmonary exercise testing (CPET)
- Peak VO2 < 15 mL/kg/min.
- Any known factor or disease that may interfere with treatment compliance or full participation in the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of macitentan on exercise capacity (measured by peak oxygen uptake [VO2]) in comparison with placebo in Fontan-palliated subjects.;Secondary Objective: To assess the effect of macitentan on long-term exercise capacity (measured by peak VO2 over 52 weeks).<br>To assess the effect of macitentan on daily Physical Activity measured by Accelometer (PA-Ac). <br>To evaluate the safety and tolerability of macitentan.;Primary end point(s): - Change in peak VO2 (oxygen uptake);Timepoint(s) of evaluation of this end point: From Baseline (Randomization/Visit 2) to Week 16 (Visit 4)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy<br>- Change in peak VO2<br>- Change in mean count per minute of daily PA-Ac<br><br>Safety<br>- Treatment-emergent AEs and SAEs<br>- AEs leading to premature discontinuation of study treatment<br><br>Pharmacokinetics (PK)<br>- Trough (pre dose) plasma concentrations;Timepoint(s) of evaluation of this end point: Efficacy<br>- from Baseline (Visit 2) over 52 weeks<br>- from Baseline (Visit 2) to Week 16 (Visit 4)<br> <br><br>Safety<br>- up to 30 days after study treatment discontinuation.<br><br>PK<br>- at Week 8 (Visit 3) and Week 16 (Visit 4), or at EOT in the case of premature study drug discontinuation.