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

• Register: EUCTR
• Last refreshed on: 7 September 2020
• Main ID: EUCTR2016-003320-23-GB
• Date of registration: 08/05/2017
• Prospective Registration: Yes
• Primary sponsor: Actelion Pharmaceuticals Ltd
• Public title: Clinical study assessing the safety and efficacy of macitentan in Fontan-palliated subjects.
• Scientific title: Prospective, multi-center, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent subjects. - RUBATO
• Date of first enrolment: 11/10/2017
• Target sample size: 134
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003320-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: adaptive If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, China, Czech Republic, Denmark, France, Germany, Ireland, New Zealand, Poland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Congenital Heart Failure
MedDRA version: 20.0 Level: PT Classification code 10045545 Term: Univentricular heart System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 21.1 Level: PT Classification code 10065950 Term: Cavopulmonary anastomosis System Organ Class: 10042613 - Surgical and medical procedures

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

Intervention(s)

Trade Name: Opsumit®
Product Name: macitentan
Product Code: ACT-064992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MACITENTAN
CAS Number: 441798-33-0
Current Sponsor code: ACT-064992
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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).
To assess the effect of macitentan on daily Physical Activity measured by Accelometer (PA-Ac).
To evaluate the safety and tolerability of macitentan.

Timepoint(s) of evaluation of this end point: From Baseline (Randomization/Visit 2) to Week 16 (Visit 4)

Primary end point(s): - Change in peak VO2 (oxygen uptake)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy
- from Baseline (Visit 2) over 52 weeks
- from Baseline (Visit 2) to Week 16 (Visit 4)


Safety
- up to 30 days after study treatment discontinuation.

PK
- at Week 8 (Visit 3) and Week 16 (Visit 4), or at EOT in the case of premature study drug discontinuation.

Secondary end point(s): Efficacy
- Change in peak VO2
- Change in mean count per minute of daily PA-Ac

Safety
- Treatment-emergent AEs and SAEs
- AEs leading to premature discontinuation of study treatment

Pharmacokinetics (PK)
- Trough (pre dose) plasma concentrations

Secondary ID(s)

AC-055H301

ISRCTN03153137

Source(s) of Monetary Support

Actelion Pharmaceuticals Ltd.

Ethics review

Status: Approved
Approval date: 11/10/2017
Contact: