Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13)

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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 combination of background PAH therapies and diuretics 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.

Exclusion Criteria:

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04811092
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Medical Director
Principal Investigator Affiliation	Merck Sharp & Dohme LLC
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Croatia, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pulmonary Arterial Hypertension
Study Website:	View Trial Website

Additional Details

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate sotatercept when added to background PAH therapy in newly diagnosed intermediate- or high risk PAH participants. Participants enrolled in the study will have a diagnosis within 12 months of study screening of symptomatic PAH (World Health Organization (WHO) Group 1, classified as functional class (FC) II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin- induced PAH, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects.

Arms & Interventions

Arms

Placebo Comparator: Placebo plus background PAH therapy

Administered subcutaneously (SC) every 21 days plus background PAH therapy

Experimental: Sotatercept plus background PAH therapy

Administered at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously (SC) every 21 days plus background PAH therapy

Interventions

Drug: - Sotatercept

Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1

Other: - Placebo

Placebo

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Phoenix, Arizona

Status

Recruiting

Address

Arizona Pulmonary Specialists ( Site 1010)

Phoenix, Arizona, 85013

Site Contact

Study Coordinator

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