A Phase 3 Study of Sotatercept in Newly Diagnosed Intermediate- and High-risk Pulmonary arterial hypertension (PAH) Patients.

• Register: EUCTR
• Last refreshed on: 30 September 2024
• Main ID: EUCTR2021-000199-12-CZ
• Date of registration: 10/09/2021
• Prospective Registration: Yes
• Primary sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
• Public title: A Phase 3 Study of Sotatercept in Newly Diagnosed Intermediate- and High-risk Pulmonary arterial hypertension (PAH) Patients.
• Scientific title: 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. - A Phase 3 Study of Sotatercept in Newly Diagnosed Intermediate- and High-risk PAH Patients
• Date of first enrolment: 29/11/2021
• Target sample size: 444
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000199-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Croatia, Czech Republic, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Michela Brambatti
• Affiliation: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA

• Name: Michela Brambatti
• Affiliation: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA

Key inclusion & exclusion criteria

Inclusion criteria: 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 enddiastolic 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 CTD - 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 REVEAL Lite 2 risk score = 6 or COMPERA 2.0 risk score = (intermediate-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. Background PAH therapy and diuretics are further defined in Section 7.2. 6. 6MWD = 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).Background PAH therapy is further defined in Section 7.2. 7. Females of childbearing potential (as defined in Appendix 4) must meet the following criteria: -Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; Agree to ongoing pregnancy testing (either urine or serum) during course of the study and until 8 weeks after the last dose of the study drug -If sexually active, with a male partner: - 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 documented informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 164
Exclusion criteria: 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, PAH associated with portal hypertension schistosomiasis-associated PAH, pulmonary veno occlusive disease and pulmonary capillary hemangiomatosis. 3. Hgb 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 (eGFR)< 30 mL/min/1.73m2 (as defined by MDRD equation) -Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels > 3 × ULN (For United Kingdom [UK], refer to the specific requirement in Appendix 6). - 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 cardiomyopathy 17. History of atrial septostomy within 180 days prior to the Screening Visit 18. Electrocardiogram (ECG) with Fridericia's corrected QT interval > 500 ms during the Screening Period (For Uk and South Korea, refer to the specific requirements in Appendix 6). 19. Personal or family history of long QT syndrome or sudden cardiac death 20. Left ventricular ejection fraction < 50% documented by a historical echocardiogram (ECHO) or cardiac magnetic resonance imaging (MRI) within the last 12 months prior to screening (if there is more than 1 assessment of left ventricular ejection fraction (LVEF), the value from the most recent measurement should be used in assessing eligibility) 21. Coronary artery disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 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. Active malignancy with the exception of ful

Age minimum:
Age maximum:
Gender: Female: yes Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension (PAH)
MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Sotatercept Product Code: ACE-011 / MK-7962 Pharmaceutical Form: Lyophilisate for solution for injection INN or Proposed INN: SOTATERCEPT CAS Number: 1001080-50-7 Current Sponsor code: ACE-011 / MK-7962 Other descriptive name: ActRIIA-IgG1Fc Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50- Pharmaceutical form of the placebo: Lyophilisate for solution for injection Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The objective of this study is to evaluate the effects of sotatercept treatment (plus background PAH therapy) versus placebo (plus background PAH therapy) on TTCW in participants who are newly diagnosed with PAH and are at intermediate or high risk of PAH disease progression.

Primary end point(s): The primary efficacy endpoint is TTCW, defined as the time from randomization to the first confirmed morbidity event or death. The events that will comprise this endpoint include the following: • All-cause death • Non-planned PAH-related hospitalization of = 24 hours in duration • Atrial septostomy • Lung transplant • Deterioration in performance in exercise testing due to PAH, defined as a decrease in 6MWD from baseline (average of screening) on 2 consecutive tests (which must be at least 4 hours apart) and at least 1 of the following: - Worsening of WHO FC from baseline - Signs/symptoms of increased right heart failure - Addition of a background PAH therapy or change PAH background therapy, delivery route to parenteral All events will be adjudicated by a blinded, independent committee of clinical experts.

Timepoint(s) of evaluation of this end point: The primary endpoint will be analyzed using a stratified log-rank test with randomization stratification factors as strata. The point estimate of the hazard ratio with 95% CI will be estimated by a Cox regression model stratified by the randomization factors.

Secondary Objective: not applicable

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: week 24

Secondary end point(s): 1. Multicomponent improvement endpoint measured by the proportion of participants achieving all of the following at Week 24 relative to baseline: -Improvement in 6MWD (increase = 30 meters [m]) -Improvement in NT-proBNP (decrease in NT-proBNP = 30%) or maintenance/achievement of NT-proBNP level < 300 ng/L -Improvement in WHO FC or maintenance of WHO FC II 2. Proportion of participants who maintain or achieve a low-risk category of REVEAL Lite 2 risk score at Week 24 versus baseline 3. Proportion of participants who maintain or achieve a low risk score at Week 24 versus baseline using the simplified French Risk score calculator 4. Change from baseline in NT-proBNP levels at Week 24 5. Proportion of participants who improve in WHO FC or maintain WHO FC II at 24 weeks from baseline 6. Change from baseline in 6MWD at Week 24 7. Change from baseline in the Physical Impacts domain score of Pulmonary Arterial Hypertension-Symptoms and Impact (PAH SYMPACT®) at Week 24 8. Change from baseline in the Cardiopulmonary Symptoms (domain score of PAH-SYMPACT)®® at Week 24 9. Change from baseline in the Cognitive/Emotional Impacts domain score of PAH-SYMPACT® at Week 24

Secondary ID(s)

2021-000199-12-BE

136150

NCT04811092

A011-13

Source(s) of Monetary Support

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA

Ethics review

Status: Approved
Approval date: 29/11/2021
Contact:

Results

• Date Posted: 01/01/1900