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

NCT03775421 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: AC-055H3022018-002821-45
• Study Type: interventional
• Target: 112
• Locations: 11 countries
• Sites: 19

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.

Conditions

Congenital Heart Disease With Fontan Circulation

Keywords

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

Outcome Measures

Primary Outcomes (17)

• 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.

  Up to 133 weeks

• 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.

  Up to 133 weeks

• 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.

  Up to 133 weeks

• 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.

  Up to 133 weeks

• 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.

  Up to 133 weeks

• Change From Baseline in Hemoglobin Over Time

  Change from baseline in hemoglobin over time was reported in this outcome measure.

  Baseline up to Week 130

• Change From Baseline in Hematocrit Over Time

  Change from baseline in hematocrit over time was reported in this outcome measure.

  Baseline up to Week 130

• 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.

  Baseline up to Week 130

• 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.

  Baseline up to Week 130

• Change From Baseline in Pulse Rate Over Time

  Change from baseline in pulse rate over time was reported in this outcome measure.

  Baseline up to Week 130

• Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time

  Change from baseline in SpO2 over time was reported in this outcome measure.

  Baseline up to Week 130

• Change From Baseline in Body Weight Over Time

  Change from baseline in body weight over time was reported in this outcome measure.

  Baseline up to Week 130

• 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.

  Baseline up to Week 130

• 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.

  Baseline up to Week 130

• Change From Baseline in Glomerular Filtration Rate (GFR) Over Time

  Change from baseline in GFR over time was reported in this outcome measure.

  Baseline up to Week 130

• Change From Baseline in Prothrombin Time Over Time

  Change from baseline in prothrombin time over time was reported in this outcome measure.

  Baseline up to Week 130

• 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.

  Baseline up to Week 130

Secondary Outcomes (2)

• Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)

  Baseline, Week 52, and Week 104

• 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

Study Arms (1)

Open-label treatment period

EXPERIMENTAL

oral administration of 10 mg macitentan once daily

Drug: macitentan 10 mg

Interventions

macitentan 10 mg DRUG

macitentan 10 mg, film-coated tablet, oral use

Open-label treatment period

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead
• Covance: collaborator
• Henry Ford Health System: collaborator
• Almac Clinical Technologies: collaborator
• ActiGraph LLC: collaborator
• Medidata Solutions: collaborator

Study Sites (19)

Massachusetts General Hospital Heart Center

Boston, Massachusetts, 02114, United States

Location

Providence Medical Research Providence Health Care

Spokane, Washington, 99202, United States

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

The Prince Charles Hospital, Adult Congenital Heart Disease Unit

Chermside, 4032, Australia

Location

Royal Children's Hospital

Parkville, 3052, Australia

Location

CHU de Québec Université Laval

Québec, Quebec, G1V 4G2, Canada

Location

Beijing Anzhen Hospital

Beijing, 100029, China

Location

Shanghai Children's Medical Center

Shanghai, 200127, China

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Rigshospitalet Kardiologisk Klinisk

Copenhagen, 2100, Denmark

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Hôpital Cardiologique Du Haut-Lévêque

Pessac, 33604, France

Location

Auckland City Hospital

Auckland, 1640, New Zealand

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i Naczyn

Krakow, 31-202, Poland

Location

Wojewodzki Szpital Specjalistyczny We Wroclawiu

Wroclaw, 51-124, Poland

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

MeSH Terms

Conditions

Univentricular Heart

Interventions

macitentan

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

The study was stopped prematurely by the sponsor because the main double-blind (DB) study (AC-055H301; NCT03153137) did not meet the primary and secondary efficacy outcome measures.

Results Point of Contact

• Title: Senior Clinical Leader PH
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Thierry Francis Briand, MD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: December 14, 2018
• Study Start: April 11, 2019
• Primary Completion: January 18, 2022
• Study Completion: January 18, 2022
• Last Updated: March 7, 2023
• Results First Posted: March 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

TW (1); GB (1); CA (1); US (2); CZ (1); AU (4); NZ (1); FR (2); CN (2); DK (1); PL (3)