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

Primary Purpose

Congenital Heart Disease With Fontan Circulation

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
macitentan 10 mg
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Heart Disease With Fontan Circulation focused on measuring Congenital Heart Failure, macitentan, Univentricular Heart, Cavopulmonary Anastomosis, Fontan circulation

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital Heart Center
  • Providence Medical Research Providence Health Care
  • Royal Adelaide Hospital
  • Royal Prince Alfred Hospital
  • The Prince Charles Hospital, Adult Congenital Heart Disease Unit
  • Royal Children's Hospital
  • CHU de Québec Université Laval
  • Beijing Anzhen Hospital
  • Shanghai Children's Medical Center
  • Fakultni nemocnice v Motole
  • Rigshospitalet Kardiologisk Klinisk
  • Hôpital Necker - Enfants Malades
  • Hôpital Cardiologique Du Haut-Lévêque
  • Auckland City Hospital
  • Uniwersyteckie Centrum Kliniczne
  • Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn
  • Wojewodzki Szpital Specjalistyczny We Wroclawiu
  • National Taiwan University Hospital
  • Queen Elizabeth Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open-label treatment period

Arm Description

oral administration of 10 mg macitentan once daily

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.
Number of Participants With Treatment-emergent Serious AEs (TESAEs)
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.
Number of Participants With TEAEs Leading to Death
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin [gram/Liter {g/L}], Platelets [giga/L {10^9 cells/L}], Leukocytes [10^9 cells/L], Lymphocytes [10^9 cells/L], Neutrophils [10^9 cells/L], Prothrombin International Normalized Ratio [PINR;Ratio], Aspartate Aminotransferase [Units/L {U/L}], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Glomerular Filtration Rate [milliliter/minute/1.73 meter square], Glucose [millimoles/L {mmol/L}], Potassium [mmol/L], Sodium [mmol/L], Triglycerides [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. >=:greater than or equal to; >:greater than; <:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.
Change From Baseline in Hemoglobin Over Time
Change from baseline in hemoglobin over time was reported in this outcome measure.
Change From Baseline in Hematocrit Over Time
Change from baseline in hematocrit over time was reported in this outcome measure.
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.
Change From Baseline in Pulse Rate Over Time
Change from baseline in pulse rate over time was reported in this outcome measure.
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Change from baseline in SpO2 over time was reported in this outcome measure.
Change From Baseline in Body Weight Over Time
Change from baseline in body weight over time was reported in this outcome measure.
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Change from baseline in GFR over time was reported in this outcome measure.
Change From Baseline in Prothrombin Time Over Time
Change from baseline in prothrombin time over time was reported in this outcome measure.
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.

Secondary Outcome Measures

Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)
Change from baseline in peak VO2 was reported in this outcome measure.
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.

Full Information

First Posted
November 21, 2018
Last Updated
March 6, 2023
Sponsor
Actelion
Collaborators
Covance, Henry Ford Health System, Almac Clinical Technologies, ActiGraph LLC, Medidata Solutions
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1. Study Identification

Unique Protocol Identification Number
NCT03775421
Brief Title
An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients.
Acronym
RUBATO OL
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
As The RUBATO DB study (NCT03153137) did not show any benefit of treatment with macitentan in Fontan-palliated participants, the sponsor has decided to terminate the RUBATO OL study (NCT03775421). No new safety observations were made.
Study Start Date
April 11, 2019 (Actual)
Primary Completion Date
January 18, 2022 (Actual)
Study Completion Date
January 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
Collaborators
Covance, Henry Ford Health System, Almac Clinical Technologies, ActiGraph LLC, Medidata Solutions

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Heart Disease With Fontan Circulation
Keywords
Congenital Heart Failure, macitentan, Univentricular Heart, Cavopulmonary Anastomosis, Fontan circulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-label treatment period
Arm Type
Experimental
Arm Description
oral administration of 10 mg macitentan once daily
Intervention Type
Drug
Intervention Name(s)
macitentan 10 mg
Intervention Description
macitentan 10 mg, film-coated tablet, oral use
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.
Time Frame
Up to 133 weeks
Title
Number of Participants With Treatment-emergent Serious AEs (TESAEs)
Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.
Time Frame
Up to 133 weeks
Title
Number of Participants With TEAEs Leading to Death
Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
Time Frame
Up to 133 weeks
Title
Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.
Time Frame
Up to 133 weeks
Title
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Description
Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin [gram/Liter {g/L}], Platelets [giga/L {10^9 cells/L}], Leukocytes [10^9 cells/L], Lymphocytes [10^9 cells/L], Neutrophils [10^9 cells/L], Prothrombin International Normalized Ratio [PINR;Ratio], Aspartate Aminotransferase [Units/L {U/L}], Bilirubin [micromoles/L {mcmol/L}], Alkaline Phosphatase [U/L], Glomerular Filtration Rate [milliliter/minute/1.73 meter square], Glucose [millimoles/L {mmol/L}], Potassium [mmol/L], Sodium [mmol/L], Triglycerides [mmol/L] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. >=:greater than or equal to; >:greater than; <:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.
Time Frame
Up to 133 weeks
Title
Change From Baseline in Hemoglobin Over Time
Description
Change from baseline in hemoglobin over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Hematocrit Over Time
Description
Change from baseline in hematocrit over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Description
Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Description
Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Pulse Rate Over Time
Description
Change from baseline in pulse rate over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Description
Change from baseline in SpO2 over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Body Weight Over Time
Description
Change from baseline in body weight over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
Description
Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Description
Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Description
Change from baseline in GFR over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Prothrombin Time Over Time
Description
Change from baseline in prothrombin time over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Title
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Description
Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.
Time Frame
Baseline up to Week 130
Secondary Outcome Measure Information:
Title
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)
Description
Change from baseline in peak VO2 was reported in this outcome measure.
Time Frame
Baseline, Week 52, and Week 104
Title
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
Description
Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.
Time Frame
Baseline, Week 26, Week 52, Week 78, and Week 104

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry Francis Briand, MD
Organizational Affiliation
Actelion
Official's Role
Study Director
Facility Information:
Facility Name
Massachusetts General Hospital Heart Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Providence Medical Research Providence Health Care
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Prince Charles Hospital, Adult Congenital Heart Disease Unit
City
Chermside
ZIP/Postal Code
4032
Country
Australia
Facility Name
Royal Children's Hospital
City
Parkville
ZIP/Postal Code
3052
Country
Australia
Facility Name
CHU de Québec Université Laval
City
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
Facility Name
Beijing Anzhen Hospital
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
Shanghai Children's Medical Center
City
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Fakultni nemocnice v Motole
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Rigshospitalet Kardiologisk Klinisk
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Hôpital Necker - Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Hôpital Cardiologique Du Haut-Lévêque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1640
Country
New Zealand
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny We Wroclawiu
City
Wrocław
ZIP/Postal Code
51-124
Country
Poland
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Queen Elizabeth Hospital
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

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

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