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.

Pulmonary Arterial Hypertension Clinical Trial

— UMBRELLA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03422328
• Other study ID #: AC-055-314
• Secondary ID: 2017-003934-10
• Status: Completed
• Phase: Phase 3
• Start date: April 5, 2018
• Est. completion date: December 27, 2023

Study information

• Verified date: February 2024
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: December 27, 2023
• Est. primary completion date: December 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Familial Primary Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Drug:
• macitentan
macitentan 10 mg, film-coated tablet, oral use

Locations

Country	Name	City	State
Belarus	Minsk Regional Clinical Hospital Of The Red Banner Of Labor	Minsk
Belgium	UZ Leuven	Leuven
France	CHRU Besancon Hopital Jean Minjoz	Besançon
France	CHU de Bordeaux - Hospital Haut-Leveque	Bordeaux (Pessac)
France	CHU de la Cavale Blanche	Brest Cedex 2
France	GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel	Bron Cedex
France	Hôpital Côte de Nacre	Caen Cedex
France	CHU Dijon	Dijon Cedex
France	CHU Grenoble	Grenoble
France	Hopital Bicêtre - Aphp Hôpitaux Universitaires Paris-Sud	Le Kremlin Bicetre cedex
France	Hôpital Cardiologique - Chru Lille	Lille Cedex
France	CHU de Limoges	Limoges Cedex
France	CHU de la Timone	Marseille cedex 5
France	CHU de Montpellier - Arnaud de Villeneuve	Montpellier
France	CHU Nantes - Hopital Nord Laënnec	Nantes Cedex 1
France	Centre Hospitalier Universitaire - de Nice - Hopital Pasteur	Nice
France	Hôpital Européen Georges Pompidou	Paris Cedex 15
France	CHU de Reims	Reims
France	Chu Rennes - Hopital Pontchaillou	Rennes
France	CHU Rouen - Hopital Charles Nicolle	Rouen
France	CHU Saint-Etienne - Hopital Nord	St Priest en Jarez Cedex
France	Nouvel Hopital Civil	Strasbourg
France	Hopital Larrey CHU de Toulouse	Toulouse Cedex 9
France	CHU de Nancy - Hopital de Brabois	Vandoeuvre les Nancy Cedex
Poland	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ	Lublin
Poland	Wojewodzki Szpital Specjalistyczny, Oddzial Kardiologiczny	Wroclaw
Russian Federation	Cardiovascular Pathology Research Institute of Siberian Branch of RAMS	Kemerovo
Russian Federation	National Medical Research Center of Cardiology of MoH of Russian Federation	Moscow
Russian Federation	Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation	Novosibirsk
Russian Federation	Federal North-West Medical Research Centre	Saint-Petersburg
Russian Federation	Federal State Budget Scientific Institution	Tomsk
Turkey	Istanbul University Istanbul Medical Faculty	Capa_Istanbul
Ukraine	CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'	Dnipro
Ukraine	Lviv Regional Clinical Hospital	Lviv

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

Belarus,  Belgium,  France,  Poland,  Russian Federation,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)