An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients. (RUBATO OL)

• ClinicalTrials.gov Identifier: NCT03775421
• Recruitment Status: Enrolling by invitation
• First Posted: December 14, 2018
• Last Update Posted: January 22, 2021
• Sponsor: Actelion
• Collaborators: Covance; Henry Ford Health System; Almac Clinical Technologies; ActiGraph LLC; Medidata Solutions
• Information provided by (Responsible Party): Actelion

Tracking Information

• First Submitted Date: November 21, 2018
• First Posted Date: December 14, 2018
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: April 11, 2019
• Estimated Primary Completion Date: November 7, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2018)

• 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: December 11, 2018)

• Change from baseline in peak oxygen uptake (VO2) [ Time Frame: From Enrollment to End-of-Treatment visit (Week 104) ]
  Peak VO2 is measured from baseline to each scheduled time point to assess the effect of macitentan on exercise capacity.
• Change from baseline in mean count per minute of daily physical activity measured by accelerometer (PA-Ac) [ Time Frame: From Enrollment to End-of-Treatment visit (Week 104) ]
  The daily physical activity (counts/min) of the subject is assessed via accelerometer during daytime. The mean count per minute of daily PA-Ac will be measured from baseline to each scheduled time point.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Congenital Heart Disease With Fontan Circulation

Intervention

Drug: macitentan 10 mg

macitentan 10 mg, film-coated tablet, oral use

Study Arms

Experimental: Open-label treatment period

oral administration of 10 mg macitentan once daily

Intervention: Drug: macitentan 10 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: December 11, 2018): 134
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2024
• Estimated Primary Completion Date: November 7, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, China, Czechia, Denmark, France, New Zealand, Poland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03775421
• Other Study ID Numbers: AC-055H302; 2018-002821-45 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Responsible Party: Actelion
• Study Sponsor: Actelion

Collaborators

• Covance
• Henry Ford Health System
• Almac Clinical Technologies
• ActiGraph LLC
• Medidata Solutions

Investigators

• Study Director: Thierry Francis Briand, MD; Actelion

• PRS Account: Actelion
• Verification Date: January 2021