A Long-term Follow-up Study of Sotatercept for PAH Treatment (MK-7962-004/A011-12)

Phase 3

Active, not recruiting

• Conditions: Pulmonary Arterial Hypertension; PAH
• Interventions: Biological: Sotatercept

• Registration Number: NCT04796337
• Lead Sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Brief Summary

This study is being conducted to assess the long-term safety, tolerability, and efficacy of sotatercept (MK-7962, formerly called ACE-011) in participants with Pulmonary Arterial Hypertension (PAH). This open-label, long-term follow-up (LTFU) study is supported by data from the PULSAR study (Phase 2, NCT03496207) in which treatment with sotatercept resulted in hemodynamic and functional improvements in the study participants, including those receiving maximal PAH therapy with double/triple drug combinations and intravenous prostacyclin.

The primary objective of this open-label, LTFU study is to evaluate the long-term safety and tolerability of sotatercept when added to background PAH therapy in adult participants with PAH who have completed prior sotatercept studies. The secondary objective is to evaluate continued efficacy in adult participants with PAH who have completed prior sotatercept studies.

Detailed Description

Participants eligible to enroll in this study will have participated in and completed the relevant study requirements of the parent PAH sotatercept clinical studies.

Participants enrolled in this study may be eligible to participate in MK-7962-038 (NCT number pending), an open-label LTFU study to evaluate the effects of sotatercept when added to background PAH therapy.

Study Timeline

• Study First Submitted: 2021-02-22
• Study First Submitted QC: 2021-03-11
• Study First Posted: 2021-03-12
• Study Start: 2021-05-12
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-11
• Primary Completion: 2026-02-27
• Study Completion: 2026-02-27

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 815

Inclusion Criteria

• Have completed their current respective PAH sotatercept clinical study and its requirements, and must not have discontinued early

• Must be willing to adhere to the study visit schedule and understand and comply with all protocol requirements

• Must have the ability to understand and provide documented informed consent

• Females of childbearing potential must:

  • Have a negative pregnancy test as verified by the investigator prior to starting study drug administration; she must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
  • If sexually active, have used, and agree to continue to use highly effective contraception in combination with a barrier method without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study drug
  • 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 drug

• Male participants must:

  • Agree to use a condom, defined as a male latex condom or non latex 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 drug

• Must agree not to participate in any other trials of investigational drugs/devices while they are enrolled in the MK-7962-004 study, except for the MK-7962-038 study

Exclusion Criteria

• Did not participate in a sotatercept PAH parent study
• Missed more than the equivalent of 4 consecutive doses between the end of parent study and the start of this study.
• Presence of an ongoing serious adverse event (SAE) that occurred during a PAH sotatercept clinical study that is assessed to be possibly or probably related to sotatercept
• Pregnant or breastfeeding females

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sotatercept Treatment	Sotatercept	Participants rolling over from a blinded parent study will begin sotatercept at a dose of 0.3 mg/kg subcutaneous (SC) injection for Visit 1. Dose will escalate to 0.7 mg/kg SC injection at Visit 2 through the remainder of the study. Participants rolling over from an unblinded parent study will continue sotatercept at their current dose and, if at a dose \<0.7 mg/kg SC injection, can titrate up to 0.7 mg/kg SC injection for the remainder of the study.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experience an Adverse Event (AE)	Up to approximately 50 months	AE is any untoward medical occurrence in a clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. The number of participants who experience an AE will be reported.
Number of Participants with Detectable Anti-Drug Antibodies (ADAs)	Up to approximately 50 months	ADAs will be detected in serum. The number of participants with detectable ADAs will be presented.
Laboratory parameters (Hematology): Concentration of Red Blood Cell Count, White Blood Cell Count, Platelet Count, Hemoglobin and Hematocrit	Up to approximately 50 months	Blood samples will be collected to determine concentration of red blood cell count, white blood cell count, platelet count, hemoglobin and hematocrit at designated timepoints up to approximately 50 months.
Laboratory parameters (Chemistry): Concentration of Blood Urea, Creatinine, Total Bilirubin, Direct Bilirubin, AST, ALT, ALP, Sodium, Potassium, Chloride, Calcium, Phosphorous, Glucose, Magnesium, Carbon Dioxide, and Albumin	Up to approximately 50 months	Blood samples will be collected to determine concentration of blood urea, creatinine, total bilirubin, direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), sodium, potassium, chloride, calcium, phosphorous, glucose, magnesium, carbon dioxide, and albumin at designated time points for up to approximately 50 months.
Change From Baseline in Body Weight	Baseline and up to approximately 48 months	Change from baseline in body weight will be reported at designated time points up to approximately 48 months.
Change From Baseline in Blood Pressure	Baseline and up to approximately 48 months	Change from baseline in systolic and diastolic blood pressure will be reported at designated time points up to approximately 48 months.
Change From Baseline in Electrocardiogram (ECG)	Baseline and up to approximately 48 months	Change from baseline in ECG (12-lead) for the determination of QTcF interval will be reported at designated time points up to approximately 48 months.
Number of Participants Who Discontinue Study Treatment Due to an AE	Up to approximately 50 months	AE is any untoward medical occurrence in a clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. The number of participants who discontinue study treatment due to an AE will be reported.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in 6-Minute Walk Distance (6MWD)	Baseline and up to approximately 48 months	The 6MWD was the distance walked in 6 minutes as a measure of functional capacity. This was assessed using the 6-minute walk test (6MWT). The change from baseline in 6MWD will be reported.
Change From Baseline in N-Terminal Pro-Hormone B-type Natriuretic Peptide (NT-proBNP) Levels	Baseline and up to approximately 48 months	NT-proBNP is a circulating biomarker that reflects myocardial stretch. The change from baseline in NT-proBNP level will be reported.
Change From Baseline in the Percentage of Participants Who Improve in modified New York Heart Association/World Health Organization Classification of Functional Status (WHO FC)	Baseline and up to approximately 48 months	The severity of participant's PAH symptoms will be graded using the WHO FC system. WHO functional classification for PAH ranges from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). Participants who improve in WHO FC were classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC. The change from baseline in the percentage of participants who improve in WHO FC will be reported.
Change From Baseline in Pulmonary Vascular Resistance (PVR)	Baseline and up to approximately 48 months	PVR is a hemodynamic variable of pulmonary circulation and was measured by right heart catheterization. The change from baseline in PVR will be reported.
Change From Baseline in Percentage of Participants Who Maintain or Achieve a Low Risk Score Using the Simplified French Risk Score Calculator	Baseline and up to approximately 48 months	The simplified French risk scoring system was based on the 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension. In this study, the noninvasive parameters were used to determine the score. 'Low risk' was defined as attaining or maintaining all 3 low-risk criteria: WHO FC I or II, 6MWD \> 440 m, and NT-proBNP \<300 ng/L. The change from baseline in percentage of participants who maintained or achieved a low risk score using the simplified French risk score calculator will be reported.

Trial Locations

Locations (189)

Pulmonary Associates, PA ( Site 1008); 🇺🇸 Phoenix, Arizona, United States

Arizona Pulmonary Specialists ( Site 1010); 🇺🇸 Scottsdale, Arizona, United States

University of Arizona ( Site 1006); 🇺🇸 Tucson, Arizona, United States

University of California San Diego ( Site 1002); 🇺🇸 La Jolla, California, United States

David Geffen School of Medicine at UCLA ( Site 1068); 🇺🇸 Los Angeles, California, United States

University of California Irvine ( Site 1086); 🇺🇸 Orange, California, United States

UC Davis - Medial Center ( Site 1064); 🇺🇸 Sacramento, California, United States

University of California San Francisco ( Site 1019); 🇺🇸 San Francisco, California, United States

Jeffrey S.Sager MD Medical Corporation ( Site 1060); 🇺🇸 Santa Barbara, California, United States

Harbor UCLA Medical Center ( Site 1028); 🇺🇸 Torrance, California, United States

Scroll for more (179 remaining)