Pulmonary Arterial HypertensionPhase 3UMBRELLANCT03422328
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.
A Phase 3 study testing macitentan in people with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension, run by Actelion at 34 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension
- What is being tested?
- macitentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 34 sitesin 7 countries
- Study dates
- 5 Apr 2018to 27 Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
34 sites in 7 countries.
34 sites in 7 countries
France22 sites
CHRU Besancon Hopital Jean Minjoz
Besançon, 25030
CHU de Bordeaux - Hospital Haut-Leveque
Bordeaux (Pessac), 33604
CHU de la Cavale Blanche
Brest, 29609
GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel
Bron, 69677
Hôpital Côte de Nacre
Caen
CHU Dijon
Dijon, 21079
CHU Grenoble
Grenoble, 38700
Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud
Le Kremlin-Bicêtre, 94275
Hôpital Cardiologique - Chru Lille
Lille, 59037
CHU de Limoges
Limoges, 87042
CHU de la Timone
Marseille, 13005
CHU de Montpellier - Arnaud de Villeneuve
Montpellier, 34295
CHU Nantes - Hopital Nord Laënnec
Nantes, 44093
Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
Nice, 06001
Hopital Europeen Georges Pompidou
Paris, 75908
CHU de Reims
Reims, 51100
Chu Rennes Hopital Pontchaillou
Rennes, 35033
CHU Rouen Hopital Charles Nicolle
Rouen, 76031
CHU Saint Etienne Hopital Nord
Saint-Priest-en-Jarez, 42277
Nouvel Hopital Civil
Strasbourg, 67091
Hopital Larrey CHU de Toulouse
Toulouse
CHU de Nancy - Hopital de Brabois
Vandœuvre-lès-Nancy, 54511
Russia5 sites
Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
Kemerovo, 650002
National Medical Research Center of Cardiology of MoH of Russian Federation
Moscow, 121552
Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation
Novosibirsk, 630055
Federal North-West Medical Research Centre
Saint Petersburg, 197341
Federal State Budget Scientific Institution
Tomsk, 634012
Poland2 sites
Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
Lublin, 20 718
Wojewodzki Szpital Specjalistyczny Oddzial Kardiologiczny
Wroclaw, 51 124
Ukraine2 sites
CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
Dnipro, 49059
Lviv Regional Clinical Hospital
Lviv, 79000
Belarus1 site
The Republican Scientific-Practical Center ''Cardiology''
Minsk, 220036
Turkey (Türkiye)1 site
Istanbul University Istanbul Medical Faculty
Capa_Istanbul, 34093
About this study
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
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.
Read the 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.
- Being tested
- macitentan
- Keywords
- macitentan, long-term safety, open-label, single-arm
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
macitentanDrug
Also called ACT-064992, JNJ-67896062
macitentan 10 mg, film-coated tablet, oral use
| Study group | Role | What they receive |
|---|---|---|
| Open-label macitentan 10 mg | Experimental | 10 mg macitentan film coated tablet, administered orally once daily Receives: Drug: macitentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Day 1 to EoS visit (an average of 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start5 Apr 2018
- Primary completion27 Dec 2023
- Study completion27 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marek Sochor, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03422328
- Sponsor's protocol ID
- AC-055-314
- Other IDs
- 2017-003934-10, 2017
- Acronym
- UMBRELLA
- Status last verified
- Apr 2025
- First submitted
- 30 Jan 2018
- Last updated
- 27 Apr 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03422328
- Acronym / sponsor ID
- UMBRELLA / AC-055-314
- Keywords
- macitentan, long-term safety, open-label, single-arm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 5 Apr 2018 (actual)
- Primary completion
- 27 Dec 2023 (actual)
- Study completion
- 27 Dec 2023 (actual)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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".
| Arm | Type | Receives |
|---|---|---|
| Open-label macitentan 10 mg | Experimental | Drug: macitentan10 mg macitentan film coated tablet, administered orally once daily |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| macitentanAlso: ACT-064992, JNJ-67896062macitentan 10 mg, film-coated tablet, oral use | Drug | Open-label macitentan 10 mg |
Primary outcome
Incident Rate of Treatment-emergent Adverse Event
Time frame: From Day 1 to End of study (EoS) visit (an average of 3 years)
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
Time frame: From Day 1 to EoS visit (an average of 3 years)
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)
Time frame: From Day 1 to EoS visit (an average of 3 years)
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
Time frame: From Day 1 to EoS visit (an average of 3 years)
Pregnancies with maternal exposure to macitentan will be recorded.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marek Sochor study director
Actelion
34 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing macitentan in people with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension, run by Actelion at 34 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in France, Russia, Poland, Ukraine, Belarus and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incident Rate of Treatment-emergent Adverse Event (time frame: From Day 1 to End of study (EoS) visit (an average of 3 years)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025.