Back to resultsA 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)
Primary Purpose
Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
macitentan
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring macitentan, long-term safety, open-label, single-arm
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent to take part in the study before any study mandated procedure.
- 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
- 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:
- Hemoglobin less than 80 gram per liter (g/L)
- Serum Aspartate aminotransferase (AST) and/or alanine aminotransferases (ALT) more than three times the upper limit of normal range
- Known and documented history of severe hepatic impairment that is Child-Pugh Class C.
- Pregnant, planning to become pregnant, or breastfeeding
- Known hypersensitivity to macitentan, its excipients, or drugs of the same class
- Planned or current treatment with another investigational treatment up to 3 months prior to Enrollment
- 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
- Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)
Sites / Locations
- Minsk Regional Clinical Hospital Of The Red Banner Of Labor
- UZ Leuven
- CHRU Besançon -Hôpital Jean Minjoz
- CHU de Bordeaux - Hospital Haut-Leveque
- CHU de la Cavale Blanche
- GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel
- Hôpital Côte de Nacre
- CHU Dijon
- CHU Grenoble
- Hopital Bicêtre - Aphp Hôpitaux Universitaires Paris-Sud
- Hôpital Cardiologique - Chru Lille
- CHU de Limoges
- CHU de la Timone
- CHU de Montpellier - Arnaud de Villeneuve
- CHU Nantes - Hopital Nord Laënnec
- Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
- Hôpital Européen Georges Pompidou
- CHU de Reims
- Chu Rennes - Hopital Pontchaillou
- CHU Rouen - Hopital Charles Nicolle
- CHU Saint-Etienne - Hôpital Nord
- Nouvel Hôpital Civil
- Hopital Larrey CHU de Toulouse
- CHU de Nancy - Hôpital de Brabois
- Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ
- Wojewodzki Szpital Specjalistyczny, Oddzial Kardiologiczny
- Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
- National Medical Research Center of Cardiology of MoH of Russian Federation
- Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation
- Federal North-West Medical Research Centre
- Federal State Budget Scientific Institution
- Istanbul University Istanbul Medical Faculty
- CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
- Lviv Regional Clinical Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open-label macitentan 10 mg
Arm Description
10 mg macitentan film coated tablet, administered orally once daily
Outcomes
Primary Outcome Measures
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.
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.
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.
Number of pregnancies with maternal exposure to macitentan
Pregnancies with maternal exposure to macitentan will be recorded.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03422328
Brief Title
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.
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 5, 2018 (Actual)
Primary Completion Date
December 20, 2023 (Anticipated)
Study Completion Date
December 20, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension
Keywords
macitentan, long-term safety, open-label, single-arm
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, single-arm, multicenter trial in which all participants roll over from a "parent study" in order to continue their dose of macitentan 10 mg once every day as already received in the "parent study".
Masking
None (Open Label)
Allocation
N/A
Enrollment
147 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open-label macitentan 10 mg
Arm Type
Experimental
Arm Description
10 mg macitentan film coated tablet, administered orally once daily
Intervention Type
Drug
Intervention Name(s)
macitentan
Other Intervention Name(s)
ACT-064992, JNJ-67896062
Intervention Description
macitentan 10 mg, film-coated tablet, oral use
Primary Outcome Measure Information:
Title
Incident Rate of Treatment-emergent Adverse Event
Description
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.
Time Frame
From Day 1 to End of study (EoS) visit (an average of 3 years)
Title
Incident rate of treatment-emergent adverse events (AEs) leading to premature discontinuation of study treatment
Description
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.
Time Frame
From Day 1 to EoS visit (an average of 3 years)
Title
Incident rate of treatment-emergent serious adverse events (SAEs)
Description
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.
Time Frame
From Day 1 to EoS visit (an average of 3 years)
Title
Number of pregnancies with maternal exposure to macitentan
Description
Pregnancies with maternal exposure to macitentan will be recorded.
Time Frame
From Day 1 to EoS visit (an average of 3 years)
Other Pre-specified Outcome Measures:
Title
Change of WHO functional class to each scheduled time point
Description
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").
Time Frame
From Day 1 to EoT visit (an average of 3 years)
Title
Assessment of survival status at End-of-Study (EoS)
Description
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.
Time Frame
From Day 1 to EoS visit (an average of 3 years)
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent to take part in the study before any study mandated procedure.
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
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:
Hemoglobin less than 80 gram per liter (g/L)
Serum Aspartate aminotransferase (AST) and/or alanine aminotransferases (ALT) more than three times the upper limit of normal range
Known and documented history of severe hepatic impairment that is Child-Pugh Class C.
Pregnant, planning to become pregnant, or breastfeeding
Known hypersensitivity to macitentan, its excipients, or drugs of the same class
Planned or current treatment with another investigational treatment up to 3 months prior to Enrollment
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
Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marek Sochor
Organizational Affiliation
Actelion
Official's Role
Study Director
Facility Information:
Facility Name
Minsk Regional Clinical Hospital Of The Red Banner Of Labor
City
Minsk
Country
Belarus
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHRU Besançon -Hôpital Jean Minjoz
City
Besançon
ZIP/Postal Code
25030
Country
France
Facility Name
CHU de Bordeaux - Hospital Haut-Leveque
City
Bordeaux (Pessac)
ZIP/Postal Code
33604
Country
France
Facility Name
CHU de la Cavale Blanche
City
Brest Cedex 2
ZIP/Postal Code
29609
Country
France
Facility Name
GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Hôpital Côte de Nacre
City
Caen Cedex
Country
France
Facility Name
CHU Dijon
City
Dijon Cedex
ZIP/Postal Code
21079
Country
France
Facility Name
CHU Grenoble
City
Grenoble
ZIP/Postal Code
38700
Country
France
Facility Name
Hopital Bicêtre - Aphp Hôpitaux Universitaires Paris-Sud
City
Le Kremlin Bicetre cedex
ZIP/Postal Code
94275
Country
France
Facility Name
Hôpital Cardiologique - Chru Lille
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
CHU de Limoges
City
Limoges Cedex
ZIP/Postal Code
87042
Country
France
Facility Name
CHU de la Timone
City
Marseille cedex 5
ZIP/Postal Code
13005
Country
France
Facility Name
CHU de Montpellier - Arnaud de Villeneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHU Nantes - Hopital Nord Laënnec
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
City
Nice
ZIP/Postal Code
06001
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris Cedex 15
ZIP/Postal Code
75908
Country
France
Facility Name
CHU de Reims
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Chu Rennes - Hopital Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
CHU Rouen - Hopital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
CHU Saint-Etienne - Hôpital Nord
City
St Priest en Jarez Cedex
ZIP/Postal Code
42277
Country
France
Facility Name
Nouvel Hôpital Civil
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Hopital Larrey CHU de Toulouse
City
Toulouse Cedex 9
Country
France
Facility Name
CHU de Nancy - Hôpital de Brabois
City
Vandoeuvre les Nancy Cedex
ZIP/Postal Code
54511
Country
France
Facility Name
Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ
City
Lublin
ZIP/Postal Code
20-718
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny, Oddzial Kardiologiczny
City
Wrocław
ZIP/Postal Code
51-124
Country
Poland
Facility Name
Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
National Medical Research Center of Cardiology of MoH of Russian Federation
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation
City
Novosibirsk
ZIP/Postal Code
630055
Country
Russian Federation
Facility Name
Federal North-West Medical Research Centre
City
Saint-Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Federal State Budget Scientific Institution
City
Tomsk
ZIP/Postal Code
634012
Country
Russian Federation
Facility Name
Istanbul University Istanbul Medical Faculty
City
Capa_Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
City
Dnipro
ZIP/Postal Code
49059
Country
Ukraine
Facility Name
Lviv Regional Clinical Hospital
City
Lviv
ZIP/Postal Code
79000
Country
Ukraine
12. IPD Sharing Statement
Learn more about this trial
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.
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