Informations générales (source: ClinicalTrials.gov)
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy in Newly Diagnosed Intermediate- and High-risk PAH Patients (HYPERION)
Interventional
Phase 3
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA (Voir sur ClinicalTrials)
mars 2022
avril 2025
05 avril 2025
The objective of this study is to evaluate the effects of sotatercept (MK-7962, formerly
called ACE-011) treatment (plus background pulmonary arterial hypertension (PAH) therapy)
versus placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in
participants who are newly diagnosed with PAH and are at intermediate or high risk of
disease progression.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Bicêtre | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 1308) - 54500 - Vandoeuvre Les Nancy - Meurthe-et-Moselle - France | Contact (sur clinicalTrials) | ||||
| C.H.U. de Tours - Hopital Bretonneau ( Site 1310) - 37000 - Tours - Indre-et-Loire - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire de Saint-Etienne ( Site 1302) - 42270 - Saint-Priest-en-Jarez - Loire - France | Contact (sur clinicalTrials) | ||||
| CHU Angers ( Site 1313) - 49933 - Angers - Maine-et-Loire - France | Contact (sur clinicalTrials) | ||||
| CHU Caen Normandie ( Site 1325) - 14033 - Caen - Calvados - France | Contact (sur clinicalTrials) | ||||
| CHU de Besancon ( Site 1303) - 25000 - Besançon - Doubs - France | Contact (sur clinicalTrials) | ||||
| CHU de Poitiers ( Site 1316) - 86000 - Poitiers - Vienne - France | Contact (sur clinicalTrials) | ||||
| CHU de Toulouse - Hopital Larrey ( Site 1315) - 31059 - Toulouse - Haute-Garonne - France | Contact (sur clinicalTrials) | ||||
| Hopital Cavale Blanche ( Site 1314) - 29200 - Brest - Bretagne - France | Contact (sur clinicalTrials) | ||||
| Hopital Haut Leveque ( Site 1312) - 33604 - Bordeaux - Gironde - France | Contact (sur clinicalTrials) | ||||
| Hopital Louis Pasteur ( Site 1311) - 06001 - Nice - Alpes-Maritimes - France | Contact (sur clinicalTrials) | ||||
| Hopital Louis Pradel ( Site 1317) - 69003 - Lyon - Auvergne - France | Contact (sur clinicalTrials) | ||||
| Hopital Nord Laennec ( Site 1309) - 44000 - Nantes - Loire-Atlantique - France | Contact (sur clinicalTrials) | ||||
| Hopitaux Universitaires de Strasbourg ( Site 1307) - 67000 - Strasbourg - Bas-Rhin - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
Eligible participants must meet all of the following criteria to be enrolled in the
study:
1. Age ≥ 18 years
2. Documented diagnostic right heart catheterization (RHC) within 12 months of
screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge
pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg,
with the diagnosis of WHO PAH Group 1 in any of the following subtypes:
- Idiopathic PAH
- Heritable PAH
- Drug/toxin-induced PAH
- PAH associated with connective tissue disease
- PAH associated with simple, congenital systemic to pulmonary shunts at least 1
year following repair
3. Symptomatic PAH classified as WHO FC II or III
4. Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite
2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies
for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or
above)
5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or
triple combination of background PAH therapies and diuretics (if any) for at least
90 days prior to screening
6. Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart,
but no longer than 1 week apart, and both values are within 15% of each other
(calculated from the highest value)
7. Females of childbearing potential must meet the following criteria:
- Have 2 negative urine or serum pregnancy tests as verified by the investigator
prior to starting study drug administration; she must agree to ongoing urine or
serum pregnancy testing during the course of the study and until 8 weeks after
the last dose of the study drug
- If sexually active with a male partner, have used highly effective
contraception without interruption, for at least 28 days prior to starting the
investigational product AND agreed to use the same highly effective
contraception in combination with a barrier method during the study (including
dose interruptions) and for 16 weeks (112 days) after discontinuation of study
treatment
- Refrain from breastfeeding a child or donating blood, eggs, or ovum for the
duration of the study and for at least 16 weeks (112 days) after the last dose
of study treatment
8. Male participants must meet the following criteria:
- Agree to use a condom, defined as a male latex condom or nonlatex condom NOT
made out of natural (animal) membrane (e.g., polyurethane), during sexual
contact with a pregnant female or a female of childbearing potential while
participating in the study, during dose interruptions, and for at least 16
weeks (112 days) following investigational product discontinuation, even if he
has undergone a successful vasectomy
- Refrain from donating blood or sperm for the duration of the study and for 16
weeks (112 days) after the last dose of study treatment
9. Ability to adhere to study visit schedule and understand and comply with all
protocol requirements
10. Ability to understand and provide written informed consent
Eligible participants must meet all of the following criteria to be enrolled in the
study:
1. Age ≥ 18 years
2. Documented diagnostic right heart catheterization (RHC) within 12 months of
screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge
pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg,
with the diagnosis of WHO PAH Group 1 in any of the following subtypes:
- Idiopathic PAH
- Heritable PAH
- Drug/toxin-induced PAH
- PAH associated with connective tissue disease
- PAH associated with simple, congenital systemic to pulmonary shunts at least 1
year following repair
3. Symptomatic PAH classified as WHO FC II or III
4. Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite
2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies
for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or
above)
5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or
triple combination of background PAH therapies and diuretics (if any) for at least
90 days prior to screening
6. Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart,
but no longer than 1 week apart, and both values are within 15% of each other
(calculated from the highest value)
7. Females of childbearing potential must meet the following criteria:
- Have 2 negative urine or serum pregnancy tests as verified by the investigator
prior to starting study drug administration; she must agree to ongoing urine or
serum pregnancy testing during the course of the study and until 8 weeks after
the last dose of the study drug
- If sexually active with a male partner, have used highly effective
contraception without interruption, for at least 28 days prior to starting the
investigational product AND agreed to use the same highly effective
contraception in combination with a barrier method during the study (including
dose interruptions) and for 16 weeks (112 days) after discontinuation of study
treatment
- Refrain from breastfeeding a child or donating blood, eggs, or ovum for the
duration of the study and for at least 16 weeks (112 days) after the last dose
of study treatment
8. Male participants must meet the following criteria:
- Agree to use a condom, defined as a male latex condom or nonlatex condom NOT
made out of natural (animal) membrane (e.g., polyurethane), during sexual
contact with a pregnant female or a female of childbearing potential while
participating in the study, during dose interruptions, and for at least 16
weeks (112 days) following investigational product discontinuation, even if he
has undergone a successful vasectomy
- Refrain from donating blood or sperm for the duration of the study and for 16
weeks (112 days) after the last dose of study treatment
9. Ability to adhere to study visit schedule and understand and comply with all
protocol requirements
10. Ability to understand and provide written informed consent
Participants will be excluded from the study if any of the following criteria are met:
1. Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5
2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus
(HIV)-associated PAH and PAH associated with portal hypertension,
schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary
capillary hemangiomatosis
3. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local
laboratory test
4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure
(BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after
a period of rest
5. Baseline systolic BP < 90 mmHg at screening
6. Pregnant or breastfeeding women
7. Any of the following clinical laboratory values at the Screening Visit:
- Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (as defined by MDRD
equation)
- Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin
levels > 3 × ULN
- Platelet count < 50,000/mm3 (< 50.0 × 109 /L)
8. Currently enrolled in or have completed any other investigational product study
within 30 days for small molecule drugs or within 5 half-lives for investigational
biologics prior to the date of documented informed consent
9. Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
10. History of pneumonectomy
11. Pulmonary function test values of forced vital capacity < 60% predicted within 1
year prior to the Screening Visit
12. Stopped receiving any PH chronic general supportive therapy (e.g., diuretics,
oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
13. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days
prior to the Screening Visit or planned initiation during the study (participants
who are stable in the maintenance phase of a program and who will continue for the
duration of the study are eligible)
14. Untreated more than mild obstructive sleep apnea
15. History of known pericardial constriction
16. History of restrictive or congestive cardiomyopathy
17. History of atrial septostomy within 180 days prior to the Screening Visit
18. Electrocardiogram with Fridericia's corrected QT interval > 500 ms during the
Screening Period
19. Personal or family history of long QT syndrome or sudden cardiac death
20. Left ventricular ejection fraction < 50% on historical echocardiogram (ECHO) within
1 year prior to the Screening Visit
21. Any current or prior history of symptomatic coronary disease (prior myocardial
infarction, percutaneous coronary intervention, coronary artery bypass graft
surgery, or cardiac anginal chest pain) in the past 6 months prior to the Screening
Visit
22. Cerebrovascular accident within 3 months prior to the Screening Visit
23. Acutely decompensated heart failure within 30 days prior to the Screening Visit, as
per investigator assessment
24. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation
valvular disease
25. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and
vasopressin) within 30 days prior to the Screening Visit
26. Has an active malignancy with the exception of fully excised or treated basal cell
carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or
expected, during the study, to be treated with radiation therapy, chemotherapy,
and/or surgical intervention, or hormonal treatment