Clinical trial NCT03775421: An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients.
Official title: Prospective, Multi-center, Single-arm, Open-label Long-term Study Assessing the Safety, Tolerability, and Effectiveness of Macitentan in Fontan-palliated Adult and Adolescent Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Congenital Heart Disease With Fontan Circulation
Keywords: Congenital Heart Failure
macitentan
Univentricular Heart
Cavopulmonary Anastomosis
Fontan circulation
Lead sponsor: Actelion
Sponsor class: INDUSTRY
Collaborators: name: Covance
name: Henry Ford Health System
name: Almac Clinical Technologies
name: ActiGraph LLC
name: Medidata Solutions
First posted: 2018-12-14
Enrollment: 112
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is designed as an open-label (OL), single-arm, multicenter long-term trial in which all adolescent (≥ 12 years) and adult male and female subjects who had previously completed in the parent RUBATO DB study (AC-055H301, NCT03153137) will enroll. The primary objective of the study is to assess the long-term safety and tolerability of macitentan. All efficacy endpoints including the ones listed below are considered as exploratory in nature.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. have a negative serum pregnancy test prior to first intake of OL study drug, and,
  2. agree to perform monthly pregnancy tests up to the end of the safety follow up (S-FU) period, and,
  3. 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 133 weeks
measure: Number of Participants With Treatment-emergent Serious AEs (TESAEs)
timeFrame: Up to 133 weeks
measure: Number of Participants With TEAEs Leading to Death
timeFrame: Up to 133 weeks
measure: Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
timeFrame: Up to 133 weeks
measure: Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
timeFrame: Up to 133 weeks
measure: Change From Baseline in Hemoglobin Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Hematocrit Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Pulse Rate Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Body Weight Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Prothrombin Time Over Time
timeFrame: Baseline up to Week 130
measure: Change From Baseline in Prothrombin International Normalized Ratio Over Time
timeFrame: Baseline up to Week 130
Secondary outcomes:
measure: Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)
timeFrame: Baseline, Week 52, and Week 104
measure: Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
timeFrame: Baseline, Week 26, Week 52, Week 78, and Week 104
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Heart Center
state: Massachusetts
city: Spokane
country: United States
facility: Providence Medical Research Providence Health Care
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital, Adult Congenital Heart Disease Unit
city: Parkville
country: Australia
facility: Royal Children's Hospital
city: Quebec
country: Canada
facility: CHU de Québec Université Laval
city: Beijing
country: China
facility: Beijing Anzhen Hospital
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Copenhagen
country: Denmark
facility: Rigshospitalet Kardiologisk Klinisk
city: Paris
country: France
facility: Hôpital Necker - Enfants Malades
city: Pessac
country: France
facility: Hôpital Cardiologique Du Haut-Lévêque
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn
city: Wrocław
country: Poland
facility: Wojewodzki Szpital Specjalistyczny We Wroclawiu
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
Study officials:
affiliation: Actelion
name: Thierry Francis Briand, MD
role: STUDY_DIRECTOR
References: