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

• ClinicalTrials.gov Identifier: NCT04796337
• Recruitment Status: Recruiting
• First Posted: March 12, 2021
• Last Update Posted: April 29, 2024
• Sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Information provided by (Responsible Party): Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Tracking Information

• First Submitted Date: February 22, 2021
• First Posted Date: March 12, 2021
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: May 12, 2021
• Estimated Primary Completion Date: September 30, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2023)

• Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: 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 Who Discontinue Study Treatment Due to an AE [ Time Frame: 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.
• Number of Participants with Detectable Anti-Drug Antibodies (ADAs) [ Time Frame: 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 [ Time Frame: 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 (Serum Chemistry): Concentration of Blood Urea, Creatinine, Total Bilirubin, Direct Bilirubin, AST, ALT, ALP, Sodium, Potassium, Chloride, Calcium, Phosphorous, Glucose, Magnesium, Carbon Dioxide, and Albumin [ Time Frame: 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.
• Laboratory parameter: Concentration of Follicle Stimulating Hormone (FSH) [ Time Frame: Up to approximately 50 months ]
  Blood samples will be collected to determine concentration of FSH level at designated time points up to approximately 50 months.
• Change From Baseline in Body Weight [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
• Laboratory parameters (Urinalysis): pH, Specific Gravity, Protein, Glucose, Bilirubin, Ketones, Blood, Leukocyte Esterase, Urobilinogen, and Nitrite [ Time Frame: Up to approximately 48 months ]
  Urine samples will be collected to determine pH, specific gravity, protein, glucose, bilirubin, ketones, blood, leukocyte esterase, urobilinogen, and nitrite at designated timepoints up to approximately 48 months.

Original Primary Outcome Measures (submitted: March 11, 2021)

• Frequency of adverse events (AEs) [ Time Frame: From date of first visit up to 200 weeks ]
• Proportion of study participants with detectable anti-drug antibodies (ADA ) [ Time Frame: From date of first visit up to 200 weeks ]
• Incidence of abnormal hematology laboratory test results [ Time Frame: From date of first visit up to 200 weeks ]
  Based upon complete blood cell count, including red blood cell count, absolute white blood cell count, hemoglobin, hematocrit and platelet count
• Incidence of abnormal clinical chemistry laboratory test results [ Time Frame: From date of first visit up to 200 weeks ]
  Based upon blood urea nitrogen, creatinine, total bilirubin, direct bilirubin, AST/ALT, alkaline phosphatase, electrolytes, glucose and carbon dioxide.
• Assessment of vital signs - body weight [ Time Frame: From date of first visit up to 200 weeks ]
• Assessment of vital signs - blood pressure (systolic/diastolic) [ Time Frame: From date of first visit up to 200 weeks ]
• Assessment of vital signs - electrocardiogram (12-lead) for the determination of QTcF interval [ Time Frame: From date of first visit up to 200 weeks ]
• Incidence of abnormal urinalysis results [ Time Frame: From date of first visit up to 200 weeks ]
  Based upon dipstick assessment of urine specific gravity, pH, glucose, bilirubin, ketone and protein

Current Secondary Outcome Measures (submitted: October 9, 2023)

• Change From Baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: 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 [ Time Frame: 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 (NYHA)/ World Health Organization classification of functional status (WHO FC) [ Time Frame: Baseline and up to approximately 48 months ]
  The severity of participant's pulmonary arterial hypertension (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) [ Time Frame: Baseline and up to approximately 48 months ]
  PVR is a hemodynamic variable of pulmonary circulation and was measured by right heart catheterization (RHC). The change from baseline in PVR will be reported.
• Overall Survival (OS) [ Time Frame: Up to approximately 78 months ]
  Overall survival is defined as the time from the start of the first sotatercept treatment in the individual participant's parent study or in this study, if the participant was completely on placebo in the parent study, to the date of death in this study, regardless of the actual cause of the participant's death.
• Change From Baseline in Percentage of Participants Who Maintain or Achieve a Low Risk Score Using the Simplified French Risk Score Calculator [ Time Frame: Baseline and up to approximately 48 months ]
  The simplified French risk scoring system was based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension (PH). 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.
• Change From Baseline in Borg Dyspnea Scale Category Ratio 10 (Borg CR 10) Score [ Time Frame: Baseline and up to approximately 48 months ]
  The Borg CR 10 Scale assesses the severity of shortness of breath as perceived by the participant. Participants will be asked: How much difficulty is your breathing causing you right now?". The score of the item ranges from 0 (no difficulty in breathing) to10 (maximum difficulty in breathing). Higher score indicates more severe dyspnea. The change from baseline in Borg CR10 scale score will be reported.

Original Secondary Outcome Measures (submitted: March 11, 2021)

• Change in 6-minute walk distance (6MWD) [ Time Frame: From initiation of treatment Visit 1 to year 4 ]
• Change in serum N-Terminal Pro-Hormone B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: From initiation of treatment Visit 1 to year 4 ]
• Change in WHO Functional Class (FC) [ Time Frame: From initiation of treatment Visit 1 to year 4 ]
• Pulmonary vascular resistance (PVR) as determined by right heart catheterization [ Time Frame: Measured at the year 4 Visit ]
• Overall Survival (OS) [ Time Frame: From initiation of treatment Visit 1 to the end of study follow-up Visit 8 weeks after year 4 ]
• Proportion of participants who maintain or achieve a low risk score using the simplified French Risk score calculator. [ Time Frame: From initiation of treatment Visit 1 to year 4 ]
  Composed of the following parameters:

  • WHO FC (I-II)
  • 6MWD >440 meters
  • NT-proBNP <50 ng/L A lower score represents a lower risk of disease progression
• Change in Borg CR10 Scale (Borg Dyspnea Scale), a measure of exercise tolerance; numerical scale from 0 to 10, with higher number representative of greater exertion. [ Time Frame: From initiation of treatment Visit 1 to year 4 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Long-term Follow-up Study of Sotatercept for PAH Treatment (MK-7962-004/A011-12)
• Official Title: An Open-label Long-term Follow-up Study to Evaluate the Effects of Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH

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 the study will have participated in and completed the relevant study requirements of the parent PAH sotatercept clinical studies.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pulmonary Arterial Hypertension
• PAH

Intervention

Biological: Sotatercept

Sotatercept subcutaneous injection at a dose of 0.3 to 0.7 mg/kg.

Other Names:

• ACE-011
• MK-7962

Study Arms

Experimental: Sotatercept Treatment

Participants rolling over from a blinded parent study will begin sotatercept at a dose of 0.3 mg/kg SC for Visit 1. Dose will escalate to 0.7 mg/kg SC at Visit 2 through remainder of the study. Participants rolling over from an unblinded parent study will continue sotatercept at their current dose and if at dose < 0.7 mg/kg SC can titrate up to 0.7 mg/kg SC for the remainder of the study.

Intervention: Biological: Sotatercept

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 11, 2021): 700
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2027
• Estimated Primary Completion Date: September 30, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Exclusion Criteria:

• Did not participate in a sotatercept PAH parent trial
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

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

Administrative Information

• NCT Number: NCT04796337
• Other Study ID Numbers: 7962-004; A011-12 ( Other Identifier: Acceleronpharma ); 2020-005061-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Original Responsible Party: Same as current
• Current Study Sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Verification Date: April 2024