History of Changes for Study: NCT05587712

Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008)

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Study Record Versions

Version	Submitted Date	Changes
1	October 17, 2022	None (earliest Version on record)
2	November 16, 2022	Study Status and Contacts/Locations
3	December 20, 2022	Study Status
4	January 6, 2023	Study Status
5	January 24, 2023	Recruitment Status, Study Status and Contacts/Locations
6	January 31, 2023	Contacts/Locations and Study Status
7	February 3, 2023	Study Status and Contacts/Locations
8	March 17, 2023	Study Status, Study Identification, Eligibility and Outcome Measures
9	May 5, 2023	Study Status and Contacts/Locations
10	June 2, 2023	Contacts/Locations and Study Status
11	August 18, 2023	Study Status, References and Contacts/Locations
12	August 25, 2023	Contacts/Locations and Study Status
13	September 22, 2023	Study Status and Contacts/Locations
14	October 19, 2023	Contacts/Locations and Study Status
15	November 23, 2023	Contacts/Locations and Study Status
16	December 22, 2023	Contacts/Locations, Study Status and References
17	January 9, 2024	Study Status, Contacts/Locations and Study Identification
18	February 8, 2024	Study Status and Contacts/Locations
19	April 5, 2024	Study Status and Contacts/Locations
20	May 3, 2024	Study Status and Contacts/Locations

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	7962-008
Brief Title:	Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008)
Official Title:	A Phase 2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sotatercept (MK-7962) in Children From 1 to Less Than 18 Years of Age With PAH on Standard of Care
Secondary IDs:	MK-7962-008 [Merck] 2022-000478-25 [EudraCT Number]

Study Status


Record Verification:	October 2022
Overall Status:	Not yet recruiting
Study Start:	November 18, 2022
Primary Completion:	September 21, 2028 [Anticipated]
Study Completion:	September 21, 2028 [Anticipated]

First Submitted:	October 17, 2022
First Submitted that Met QC Criteria:	October 17, 2022
First Posted:	October 20, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	October 17, 2022
Last Update Posted:	October 20, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Merck Sharp & Dohme LLC
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


Brief Summary:	The primary objectives of the study are to evaluate the safety and tolerability, and pharmacokinetics (PK) of sotatercept over 24 weeks of treatment in children ≥1 to <18 years of age with PAH World Health Organization (WHO) Group 1 on standard of care (SoC). There is no formal hypothesis.
Detailed Description:

Conditions


Conditions:	Pulmonary Arterial Hypertension
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 2
Interventional Study Model:	Single Group Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	42 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Children ≥1 to <18 years old Participants will receive a subcutaneous (SC) injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.	Drug: Sotatercept SC injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines. Other Names: MK-7962

Outcome Measures


Primary Outcome Measures:
1.	Serum Trough Concentration (Ctrough) of Sotatercept [ Time Frame: Predose Day 1, Day 21, Day 42, Day 63, Day 84, Day105, Day 126, Day 147, Day 168, Day 189. Postdose Day 7, Day 14, Day 64, Day 69 and Day 76 ] Ctrough was the lowest concentration of Sotatercept in serum just before the next dose. Blood samples will be collected at multiple time points to estimate the Ctrough of Sotatercept.
2.	Area Under the Curve at Steady State (AUCss) of Sotatercept [ Time Frame: Predose Day 1, Day 21, Day 42, Day 63, Day 84, Day105, Day 126, Day 147, Day 168, Day 189. Postdose Day 7, Day 14, Day 64, Day 69 and Day 76 ] Blood samples will be collected at multiple time points to estimate the AUCss of Sotatercept.
3.	Area Under the Curve from 0 to 3 weeks (AUC0-3 weeks) of Sotatercept [ Time Frame: Predose Day 1, Day 7, Day 14, and Predose Day 21 ] Blood samples will be collected at Predose Day 1, Day 7, Day 14, and Predose Day 21 to estimate the AUC0-3 weeks of Sotatercept.
4.	Percentage of Participants Who Experience at Least 1 Adverse Event (AE) [ Time Frame: Up to 24 weeks ] An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs will be assessed.
5.	Percentage of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to 24 weeks ] An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study drug due to an AE regardless of study completion status will be assessed.
6.	Laboratory Parameter (Hematology): Concentration of Hemoglobin [ Time Frame: Up to 24 weeks ] Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The concentration of hemoglobin will be presented.
7.	Laboratory Parameter (Hematology): Hematocrit [ Time Frame: Up to 24 weeks ] Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The hematocrit will be presented.
8.	Laboratory Parameter (Hematology): Red Blood Cell (RBC) Count [ Time Frame: Up to 24 weeks ] Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The RBC count will be presented.
9.	Laboratory Parameter (Hematology): Reticulocyte Count [ Time Frame: Up to 24 weeks ] Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The reticulocyte count will be presented.
10.	Laboratory Parameter (Hematology): Platelet Count [ Time Frame: Up to 24 weeks ] Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The platelet count will be presented.
11.	Blood Pressure (BP) [ Time Frame: Up to 24 weeks ] BP will be assessed while the participant was seated after a period of rest in a quiet setting with no distractions (eg, television and cell phones).
12.	Titer of Anti-drug Antibody (ADA) to Sotatercept [ Time Frame: Up to 24 weeks ] ADA to Sotatercept will be assessed.
Secondary Outcome Measures:
1.	Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2) [ Time Frame: Baseline and Week 24 ] 6MWD will be assessed using the 6-minute walk test (6MWT).
2.	Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) [ Time Frame: Baseline and Week 24 ] A two-dimensional echocardiogram (ECHO) will be performed with the results interpreted by a blinded independent central review (BICR) at baseline and after 24 weeks of treatment. The change from baseline in TAPSE will be reported.
3.	Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP) [ Time Frame: Baseline and Week 24 ] A two-dimensional ECHO will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in PASP will be reported.
4.	Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC) [ Time Frame: Baseline and Week 24 ] A two-dimensional ECHO will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in RVFAC will be reported.
5.	Mean Change from Baseline in Eccentricity Index [ Time Frame: Baseline and Week 24 ] A two-dimensional ECHO will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in eccentricity index will be reported.
6.	Mean Change from Baseline in Right Ventricular (RV) Function (Cohort 1 Only) [ Time Frame: Baseline and Week 24 ] Cardiac magnetic imaging (MRI) will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in eccentricity index will be reported.
7.	Mean Change from Baseline on Cardiac Output (Cohort 1 Only) [ Time Frame: Baseline and Week 24 ] Cardiac magnetic imaging (MRI) will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in cardiac output will be reported.
8.	Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohort 1 Only) [ Time Frame: Baseline and Week 24 ] Cardiac magnetic imaging (MRI) will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in PAP will be reported.
9.	Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score [ Time Frame: Baseline and Week 24 ] PedsQL Measurement Model is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The change from baseline in the PedsQL generic core scale will be reported.
10.	Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline and Week 24 ] The change from baseline in plasma NT-proBNP levels will be reported.
11.	Percentage of Participants Who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC) [ Time Frame: Baseline and Week 24 ] The severity of an individual's PAH symptoms will be graded using the WHO FC system. WHO functional classification for PAH range 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). The change from baseline in WHO FC will be classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC.

Eligibility


Minimum Age:	1 Year
Maximum Age:	17 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria Documented, historic diagnostic right heart catheterization (RHC) any time before Screening confirming the diagnosis of PAH WHO Group 1 in any of the following subtypes: Idiopathic pulmonary arterial hypertension (IPAH) Heritable PAH Drug/toxin-induced PAH PAH associated with connective tissue disease PAH-congenital heart disease (CHD) with shunt closure >6 months before Screening and subsequently confirmed by RHC before Screening PAH with coincidental shunt. Must be on a stable dose(s) of background PAH therapy (phosphdiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs), soluble guanylate cyclase stimulators (sGCS), or prostanoids [including subcutaneous and intravenous]) If male, agree to the following during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention: Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent or Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below: Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. If female, must be either not a WOCBP or use a contraceptive method that is highly effective or be abstinent from heterosexual intercourse during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention If male, agrees to refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study intervention If female, agrees to refrain from 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 intervention Exclusion Criteria History of left-sided heart disease, including valvular disease (eg, moderate or greater mitral or aortic regurgitation or stenosis), left ventricular outflow tract obstruction, and/or left heart failure (eg, restrictive or dilated cardiomyopathy) Severe (as based on the opinion of the investigator) congenital abnormalities of the lung, thorax, and/or diaphragm History of Eisenmenger syndrome Unrepaired or residual cardiac shunt Diagnosis of pulmonary veno-occlusive diseases, pulmonary capillary hemangiomatosis, or overt signs of capillary and/or venous involvement PAH associated with portal hypertension Known visceral (lung, liver, or brain) arteriovenous malformation(s) History of full or partial pneumonectomy Untreated more than mild obstructive sleep apnea History of known pericardial constriction Family history of sudden cardiac death or long QT syndrome Any current or prior history of symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months before Screening Cerebrovascular accident within 3 months before Screening Prior exposure to sotatercept or luspatercept or has had an allergic reaction to any of their excipients

Contacts/Locations


Study Officials:	Medical Director Study Director Merck Sharp & Dohme LLC
Locations:

IPDSharing


Plan to Share IPD:	Yes http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL: http://engagezone.msd.com/ds_documentation.php

References


Citations:
Links:
Available IPD/Information: