A Clinical Study to Investigate the Long-term Safety of the Drug Macitentan in Patients With Pulmonary Hypertension Who Were Previously Treated With Macitentan in Clinical Studies. (UMBRELLA)

mUlticenter, Single-arM, Open-laBel, Long-teRm Safety Study With macitEntan in Patients With puLmonary Arterial Hypertension previousLy Treated With mAcitentan in Clinical Studies

The aim of the trial is to study the long-term safety of macitentan and to provide continued treatment with macitentan to patients with pulmonary arterial hypertension (PAH) and Chronic thromboembolic pulmonary hypertension (CTEPH) who were previously treated with macitentan in clinical studies.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension; Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Drug: macitentan

Detailed Description

The purpose of this study is to provide continued treatment with macitentan to subjects with PAH or CTEPH who participated in "parent studies" and to continue to accrue long-term safety data. The design of this study is widely used in clinical programs to give participants in a clinical study access to an effective study treatment beyond completion of the parent study. This is considered the best option to collect long-term safety and tolerability information of macitentan 10 mg and survival status of participants with PAH and CTEPH. "Parent study/studies" refer to a number of clinical studies with macitentan that are conducted in different clinical classification of PAH and CTEPH (NCT00667823, NCT02112487, NCT02310672, NCT02968901, NCT02558231, NCT02382016, NCT02060721) and may be completed before the participants have access to commercial macitentan in their country of residence. The "parent studies" are fully or partially running in countries where no access to commercial macitentan is expected in the near future.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 220036
    • The Republican Scientific-Practical Center ''Cardiology''
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• France
  • Besancon, France, 25030
    • CHRU Besancon Hopital Jean Minjoz
  • Bordeaux (Pessac), France, 33604
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Brest Cedex 2, France, 29609
    • CHU de la Cavale Blanche
  • Bron Cedex, France, 69677
    • GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel
  • Caen Cedex, France
    • Hôpital Côte De Nacre
  • Dijon Cedex, France, 21079
    • CHU Dijon
  • Grenoble, France, 38700
    • CHU Grenoble
  • Le Kremlin Bicetre cedex, France, 94275
    • Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud
  • Lille Cedex, France, 59037
    • Hôpital Cardiologique - Chru Lille
  • Limoges Cedex, France, 87042
    • CHU de Limoges
  • Marseille cedex 5, France, 13005
    • CHU de la Timone
  • Montpellier, France, 34295
    • CHU de Montpellier - Arnaud de Villeneuve
  • Nantes Cedex 1, France, 44093
    • CHU Nantes - Hopital Nord Laënnec
  • Nice, France, 06001
    • Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
  • Paris Cedex 15, France, 75908
    • Hopital Europeen Georges Pompidou
  • Reims, France, 51100
    • CHU de Reims
  • Rennes, France, 35033
    • Chu Rennes Hopital Pontchaillou
  • Rouen, France, 76031
    • CHU Rouen Hopital Charles Nicolle
  • St Priest en Jarez Cedex, France, 42277
    • CHU Saint Etienne Hopital Nord
  • Strasbourg, France, 67091
    • Nouvel Hôpital Civil
  • Toulouse Cedex 9, France
    • Hopital Larrey CHU de Toulouse
  • Vandoeuvre les Nancy Cedex, France, 54511
    • CHU de Nancy - Hopital de Brabois
• Poland
  • Lublin, Poland, 20 718
    • Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
  • Wroclaw, Poland, 51 124
    • Wojewodzki Szpital Specjalistyczny Oddzial Kardiologiczny
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
  • Moscow, Russian Federation, 121552
    • National Medical Research Center of Cardiology of MoH of Russian Federation
  • Novosibirsk, Russian Federation, 630055
    • Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation
  • Saint-Petersburg, Russian Federation, 197341
    • Federal North-West Medical Research Centre
  • Tomsk, Russian Federation, 634012
    • Federal State Budget Scientific Institution
• Turkey
  • Capa_Istanbul, Turkey, 34093
    • Istanbul University Istanbul Medical Faculty
• Ukraine
  • Dnipro, Ukraine, 49059
    • CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
  • Lviv, Ukraine, 79000
    • Lviv Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent to take part in the study before any study mandated procedure.
2. Participants from one of the parent studies and: a) the sponsor has decided to terminate the parent study in that country and b) the participant has completed the end of treatment (EOT) Visit of the parent study
3. Women of childbearing potential are able to take part in the study if the following applies: a) Urine pregnancy test is negative at Enrollment; b) Agreement to perform monthly urine or serum pregnancy tests during the study and up to at least 30 days after the study treatment discontinuation; and c) Agreement to adhere to the planned contraception scheme from Enrollment up to at least 30 days after study treatment discontinuation

Exclusion Criteria:

1. Hemoglobin less than 80 gram per liter (g/L)
2. Serum Aspartate aminotransferase (AST) and/or alanine aminotransferases (ALT) more than three times the upper limit of normal range
3. Known and documented history of severe hepatic impairment that is Child-Pugh Class C.
4. Pregnant, planning to become pregnant, or breastfeeding
5. Known hypersensitivity to macitentan, its excipients, or drugs of the same class
6. Planned or current treatment with another investigational treatment up to 3 months prior to Enrollment
7. Any known factor or disease that may interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease
8. Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-label macitentan 10 mg; 10 mg macitentan film coated tablet, administered orally once daily	Drug: macitentan; macitentan 10 mg, film-coated tablet, oral use; Other Names: ACT-064992; JNJ-67896062

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident Rate of Treatment-emergent Adverse Event	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A treatment-emergent AE is any AE temporally associated with the use of study treatment.	From Day 1 to End of study (EoS) visit (an average of 3 years)
Incident rate of treatment-emergent adverse events (AEs) leading to premature discontinuation of study treatment	Any AE will be recorded that 1) is (temporally) associated with the use of study treatment whether or not considered by the investigator as related to study treatment and 2) leads to premature discontinuation of study medication.	From Day 1 to EoS visit (an average of 3 years)
Incident rate of treatment-emergent serious adverse events (SAEs)	Any SAE as defined by the ICH guidelines will be recorded. Any hepatic AE that leads to discontinuation of study treatment will be defined as SAE.	From Day 1 to EoS visit (an average of 3 years)
Number of pregnancies with maternal exposure to macitentan	Pregnancies with maternal exposure to macitentan will be recorded.	From Day 1 to EoS visit (an average of 3 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of WHO functional class to each scheduled time point	The proportion of patients who worsened, remain unchanged or improved from baseline to each scheduled time-point in WHO function will be calculated, where baseline is the initial baseline from the "parent study" (or the double-blind core study preceding the "parent study").	From Day 1 to EoT visit (an average of 3 years)
Assessment of survival status at End-of-Study (EoS)	Time to death of all causes up to EoS from the date of randomization or enrollment in the "parent study" (or the double-blind core study preceding the "parent study") will be estimated.	From Day 1 to EoS visit (an average of 3 years)

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Marek Sochor, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Actual): December 27, 2023
• Study Completion (Actual): December 27, 2023

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: open-label; macitentan; long-term safety; single-arm
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Hypertension; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Endothelin A Receptor Antagonists; Endothelin Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055-314; 2017-003934-10 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No