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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03775421

Acronym

RUBATO OL

Enrollment

112

Registered

2018-12-14

Start date

2019-04-11

Completion date

2022-01-18

Last updated

2023-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Heart Disease With Fontan Circulation

Keywords

Congenital Heart Failure, macitentan, Univentricular Heart, Cavopulmonary Anastomosis, Fontan circulation

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.

Interventions

DRUGmacitentan 10 mg

macitentan 10 mg, film-coated tablet, oral use

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

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.

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Prothrombin International Normalized Ratio Over Time	Baseline up to Week 130	Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time	Baseline up to Week 130	Change from baseline in GFR over time was reported in this outcome measure.
Change From Baseline in Prothrombin Time Over Time	Baseline up to Week 130	Change from baseline in prothrombin time over time was reported in this outcome measure.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to 133 weeks	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)	Up to 133 weeks	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	Up to 133 weeks	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	Up to 133 weeks	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	Up to 133 weeks	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	Baseline up to Week 130	Change from baseline in hemoglobin over time was reported in this outcome measure.
Change From Baseline in Hematocrit Over Time	Baseline up to Week 130	Change from baseline in hematocrit over time was reported in this outcome measure.
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time	Baseline up to Week 130	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	Baseline up to Week 130	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	Baseline up to Week 130	Change from baseline in pulse rate over time was reported in this outcome measure.
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time	Baseline up to Week 130	Change from baseline in SpO2 over time was reported in this outcome measure.
Change From Baseline in Body Weight Over Time	Baseline up to Week 130	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	Baseline up to Week 130	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	Baseline up to Week 130	Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.

Secondary

Measure	Time frame	Description
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)	Baseline, Week 26, Week 52, Week 78, and Week 104	Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)	Baseline, Week 52, and Week 104	Change from baseline in peak VO2 was reported in this outcome measure.

Countries

Australia, Canada, China, Czechia, Denmark, France, New Zealand, Poland, Taiwan, United Kingdom, United States

Participant flow

Pre-assignment details

1 participant was enrolled twice with 2 different participant IDs but only 111 participants were enrolled in the study.

Participants by arm

Arm	Count
Macitentan 10 mg Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.	111
Total	111

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Lost to Follow-up	2
Overall Study	Physician Decision	3
Overall Study	Study Terminated by Sponsor	94
Overall Study	Withdrawal by Subject	10

Baseline characteristics

Characteristic	Macitentan 10 mg
Age, Continuous	25.1 years STANDARD_DEVIATION 7.04
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	12 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants
Race/Ethnicity, Customized Asian	13 Participants
Race/Ethnicity, Customized Black or African American	0 Participants
Race/Ethnicity, Customized More than one race	0 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants
Race/Ethnicity, Customized Other	11 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants
Race/Ethnicity, Customized White	87 Participants
Region of Enrollment AUSTRALIA	10 Participants
Region of Enrollment CANADA	4 Participants
Region of Enrollment CHINA	5 Participants
Region of Enrollment CZECH REPUBLIC	16 Participants
Region of Enrollment DENMARK	17 Participants
Region of Enrollment FRANCE	7 Participants
Region of Enrollment NEW ZEALAND	2 Participants
Region of Enrollment POLAND	23 Participants
Region of Enrollment TAIWAN	6 Participants
Region of Enrollment UNITED KINGDOM	3 Participants
Region of Enrollment UNITED STATES	18 Participants
Sex: Female, Male Female	34 Participants
Sex: Female, Male Male	77 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 111
other Total, other adverse events	34 / 111
serious Total, serious adverse events	18 / 111