Congenital Heart Disease With Fontan Circulation

The aim of this open-label (OL) trial is to study the long-term use of macitentan for up to 2 years in Fontan-palliated adult and adolescent patients beyond the 52 weeks of treatment in the parent RUBATO double-blind (DB) study (AC-055H301, NCT03153137). This OL trial studies the long-term effect of macitentan in Fontan-palliated patients as it is not known if the effect of macitentan is sustained beyond 52 weeks (end of the parent RUBATO DB study). In addition, the trial also studies the long-term safety of macitentan as this is also unknown. Furthermore, the opportunity will be given to patients who were on placebo in the parent RUBATO DB study to receive macitentan 10 mg and benefit from a potentially active treatment.

Macitentan

ACT-064992 (Macitentan)

tablet

10 mg

Primary Outcome Measures :
Frequency of treatment-emergent adverse events (AEs), serious AEs and AEs leading to death [ Time Frame: From Enrollment to End-of-Study visit (Week 104 + 30 days safety follow-up) ]
Treatment-emergent AEs and SAEs are captured up to 30 days after OL treatment discontinuation (End-of-Treatment visit). A treatment-emergent AE is any AE temporally associated with the use of study treatment (from OL treatment initiation until 30 days after OL treatment discontinuation) whether or not considered by the investigator as related to study treatment.

Number of AEs leading to premature discontinuation of study treatment [ Time Frame: From Enrollment to End-of-Treatment visit (Week 104) ]
Number of subjects with an AE assessed by the investigator as leading to discontinuation of study treatment.

Frequency of treatment-emergent marked laboratory abnormalities up to 30 days after study treatment discontinuation [ Time Frame: From Enrollment to End-of-Study visit (Week 104 + 30 days safety follow-up) ]
Laboratory abnormalities are laboratory values below of above the normal range. The definitions of marked abnormal values are based mainly on the Common Terminology Criteria for Adverse Events (CTCAE).

Incident rate of changes in laboratory parameters over time [ Time Frame: From Enrollment to End-of-Study visit (Week 104 + 30 days safety follow-up) ]
Laboratory parameters (hematology, clinical chemistry) are assessed at every visit from baseline (enrollment) to End-of-Study visit.

Change in pulse rate (PR) over time [ Time Frame: From Enrollment to End-of-Treatment visit (Week 104) ]
PR will be assessed at all scheduled visits from baseline (enrollment) to End-of-Treatment visit.

Change in peripheral oxygen saturation (SpO2) over time [ Time Frame: From Enrollment to End-of-Treatment visit (Week 104) ]
SpO2 will be assessed at all scheduled visits from baseline (enrollment) to End-of-Treatment visit.

Change in blood pressure (BP) over time [ Time Frame: From Enrollment to End-of-Treatment visit (Week 104) ]
Systolic and diastolic blood pressure will be assessed at all scheduled visits from baseline (enrollment) to End-of-Treatment visit.

Inclusion Criteria:

Written informed consent/assent from the subject and/or a legal representative prior to initiation of any study-mandated procedures.
Subjects who have completed Week 52 of the parent AC-055H301/RUBATO DB study (NCT03153137)
Women of childbearing potential must:

have a negative serum pregnancy test prior to first intake of OL study drug, and,
agree to perform monthly pregnancy tests up to the end of the safety follow up (S-FU) period, and,
use reliable methods of contraception from enrollment up to at least 30 days after study treatment discontinuation.

Exclusion Criteria:

Clinical worsening leading to medical interventions including reoperation of Fontan circulation (Fontan take-down) during the enrollment period
Systolic blood pressure < 90 mmHg (< 85 mmHg for subjects < 18 years old and < 150 cm of height) at rest
Criteria related to macitentan use
Any known factor or disease that may interfere with treatment compliance or full participation in the study