Clinical trial NCT05179876: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option
Official title: A Prospective, Open-label, Platform Study for Long-term Follow-up of Participants Using Study Intervention in Pulmonary Hypertension Parent Studies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hypertension, Pulmonary
Keywords: Chronic thromboembolic pulmonary hypertension (CTEPH)
pulmonary arterial hypertension (PAH)
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2022-01-05
Enrollment: 280
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, open-label, extension study, with a platform-study design for long-term safety follow-up of participants using study intervention as in their respective pulmonary hypertension (PH) parent study (that is, pulmonary arterial hypertension \[PAH\] or chronic thromboembolic pulmonary hypertension \[CTEPH\]). Participants who have completed a parent study, that benefit from their study intervention maintenance and have no adequate alternative local treatment option (access to the study intervention or an equivalent approved therapy) will be enrolled in this study.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to enable participants with pulmonary hypertension (PH) currently treated with study intervention(s) in a clinical study (parent studies \[NCT03422328, NCT03904693,NCT04565990, NCT02932410, NCT03492177, and NCT04175600\]), to continue to benefit from the intervention after closure of the parent study in case they have no alternative means of access to the study intervention. This study will allow assessment of the long-term safety of each study intervention.


Eligibility criteria: Inclusion Criteria:

* Participant must sign an informed consent form (ICF) (or their legally designated representative must sign) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study
* Participant treated with oral macitentan or selexipag or fixed dose combination (FDC) of macitentan 10 milligrams (mg) and tadalafil 40 mg at the end of a sponsor parent study and: a) the indication of the parent study is included in the intervention-specific appendices (ISA) (pulmonary arterial hypertension \[PAH\]; b) participant has completed the parent study; c) no alternative means of access to study intervention (or equivalent approved therapy) have been identified; d) participant may continue to benefit from treatment with the study intervention; e) Participant is at least 18 years old for macitentan/tadalafil FDC, and at least 2 years old for macitentan or selexipag
* A female participant of childbearing potential must: a) have a negative urine or serum pregnancy test prior to first intake of study intervention; b) agree to perform monthly urine pregnancy test up to the end of the safety follow-up period; c) If heterosexually active, agree to follow contraceptive methods until 30 days after the last intake of the study intervention. For pediatric female participants: It is the responsibility of the investigator to ensure appropriate counselling, including consultation with a specialist (if needed), to the participant and/or parent(s)/ legally designated representative (LDR)(s) on the acceptable method of contraception

Exclusion Criteria:

General:

* Participants prematurely discontinued from the study intervention in their parent study
* Female participant being pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study
* Planned or current treatment with another investigational treatment

Macitentan-specific:

* Known allergies, hypersensitivity, or intolerance to macitentan or its excipients
* Hemoglobin less than (\<) 80 grams per liter (g/L)
* Serum aspartate (AST) and/or alanine aminotransferases (ALT) greater than (\>) 3\* upper limit of normal (ULN)
* Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class (Child-Pugh score) should be fully assessed and documented in the source documents at screening

Selexipag-specific:

* Known allergies, hypersensitivity, or intolerance to selexipag or its excipients
* Suspected or known pulmonary veno-occlusive disease (PVOD)
* Uncontrolled thyroid disease
* Severe coronary heart disease or unstable angina, myocardial infarction within the last 6 months, decompensated cardiac failure (if not under close medical supervision), severe arrhythmia, cerebrovascular events (for example, transient ischemic attack, stroke) within the last 3 months, or congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension (PH)
* Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class (Child-Pugh score) should be fully assessed and documented in the source documents at screening
* Children only: (a) Current suspicion of intussusception or ileus or gastrointestinal obstruction, per the investigator's judgment; (b) hemoglobin or hematocrit \<75 percent (%) of the lower limit of normal range

Macitentan/tadalafil FDC-specific:

* Known allergies, hypersensitivity, or intolerance to macitentan or tadalafil or their excipients
* Hemoglobin \<80 g/L
* Serum aspartate (AST) and/or alanine aminotransferases (ALT) \>3\* ULN range
* Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class should be fully assessed and documented in the source documents at screening
* Severe renal impairment (estimated glomerular filtration rate \[eGF\]/creatinine clearance \<30 milliliter per minute \[mL/min\])

Primary outcomes:
measure: Frequency of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline until End of Study (EOS) (up to 84 months)
measure: Frequency of TEAEs Leading to Discontinuation
timeFrame: Baseline until EOS (up to 84 months)
measure: Frequency of Serious Adverse Events (SAEs)
timeFrame: Baseline until EOS (up to 84 months)
measure: Frequency of Deaths
timeFrame: Baseline until EOS (up to 84 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: The Republican Scientific-Practical Center ''Cardiology''
city: Minsk
country: Belarus
facility: Minsk Regional Clinical Hospital Of The Red Banner Of Labor
city: Leuven
country: Belgium
facility: UZ Leuven
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
city: Beijing
country: China
facility: Beijing Anzhen Hospital
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Xi'An
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Bialystok
country: Poland
facility: Klinika Kardiologii Z Oddzialem Intensywnego Nadzoru Kardiologicznego UM W Bialymstoku
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
city: Katowice
country: Poland
facility: SPSK nr 7 SUM w Katowicach Gornoslaskie Centrum Medyczne im Prof Leszka Gieca
city: Lodz
country: Poland
facility: Oddzial Kardiologii Wojewodzki Szpital Specjalistyczny im W Bieganskiego
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
city: Szczecin
country: Poland
facility: SPSK2 PUM Klinika Kardiologii
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalist Osrodek Badawczo Rozwojowy
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu
city: Kemerovo
country: Russian Federation
facility: Scientific and Research Institution of Cardiovascular Diseases Complex Problems
city: St Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution
city: Tomsk
country: Russian Federation
facility: Institute of Cardiology of Tomsk National Research Medical Center of Rus Academy of Sciences
city: Durban
country: South Africa
facility: Abdullah, IA
city: Lenasia
country: South Africa
facility: Dr Kalla
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang-Gung Memorial Hospital, LinKou Branch
city: Dnipro
country: Ukraine
facility: Municipal Inst. Of Dnipropetrovsk Region. Council
city: Kyiv
country: Ukraine
facility: State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
Study officials:
affiliation: Actelion
name: Actelion Pharmaceuticals Ltd Clinical Trial
role: STUDY_DIRECTOR
References: