Pulmonary arterial hypertension MedDRA version: 21.1 Level: LLT Classification code 10037403 Term: Pulmonary hypertension NOS System Organ Class: 100000004855
Conditions
Interventions
Product Name: Sotatercept
Product Code: MK-7962
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Sotatercept
CAS Number: 1001080-50-7
Current Sponsor code: MK-7962
Con
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female participants =1 to 6 months before Screening and subsequently confirmed by RHC before Screening - PAH with coincidental shunt 3. For the above-mentioned historical RHC, diagnostic criteria will be mean pulmonary artery pressure =20 mmHg at rest, pulmonary capillary wedge pressure or left ventricular end-diastolic pressure =15 mmHg, and PVR indexed to body surface area, =3.0 WU.m2 4. PAH classified as WHO FC I or symptomatic PAH classified as WHO FC II to IV 5. Participants must be on a stable dose(s) of background PAH therapy: - WHO FC I to III: single, double, or triple background PAH therapy for at least 12 weeks before SCR and during SCR - WHO FC IV: must be clinically stable and on stable doses of maximum tolerated double or triple background PAH therapy for at least 30 days before SCR and during SCR 6. Arterial BP at Screening within normal range for the age, gender, and height percentiles as follows: - Cohort 1: systolic BP <120 mmHg and diastolic BP <80 mmHg - Cohorts 2, 3, and 4: systolic and diastolic BP <90th percentile based on the corresponding age ranges as outlined in National High Blood Pressure Education Program, 2004 7. Left ventricular ejection fraction =50% on the ECHO at Screening 8. If male, agrees to the following during the intervention period and for at least 16 weeks 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 WOCBP who is not currently pregnant - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Not a WOCBP OR • A WOCBP and: - Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 16 weeks after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies - Has a negative highly sensitive pregnancy test (urine or serum as requir
Exclusion criteria
Exclusion criteria: 1. 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) 2. Severe (as based on the opinion of the investigator) congenital or developmental abnormalities of the lung, thorax, and/or diaphragm 3. History of Eisenmenger syndrome, Potts shunt, atrial septostomy within 180 days prior to the screening visit, or atrial septostomy with Eisenmenger physiology 4. Unrepaired or residual cardiac shunt with Qp/Qs >1.5 5. Diagnosis of pulmonary veno-occlusive diseases, pulmonary capillary hemangiomatosis, or overt signs of capillary and/or venous involvement 6. PAH associated with portal hypertension 7. Known visceral (lung, liver, or brain) arteriovenous malformation(s) 8. History of full or partial pneumonectomy 9. Untreated more than mild obstructive sleep apnea 10. History of known pericardial constriction 11. Family history of sudden cardiac death or long QT syndrome 12. 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 13. Cerebrovascular accident within 3 months before Screening 14. Prior exposure to sotatercept or luspatercept or has had an allergic reaction to any of their excipients 15. Currently enrolled in or has completed a study with any other investigational products (small molecule drugs or biologics) within 30 days or 5 half-lives of that investigational product (whichever is longer) before Screening 16. Screening platelet count 1 g/g 19. Screening AST and/or ALT >3X ULN 20. Screening ECG with Fridericia’s corrected QT interval (QTcF) >500 ms (or >550 ms, if right bundle branch block is present) 21. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety and tolerability of sotatercept over 24 weeks of treatment 2. To evaluate the PK of sotatercept over 24 weeks of treatment;Secondary Objective: 1. To evaluate the pharmacodynamics of sotatercept over 24 weeks of treatment;Primary end point(s): 1. Serum Trough Concentration (Ctrough) of Sotatercept 2. Area Under the Curve at Steady State (AUCss) of Sotatercept 3. Area Under the Curve from 0 to 3 weeks (AUC0-3 weeks) of Sotatercept 4. Percentage of Participants Who Experience at Least 1 Adverse Event (AE) 5. Percentage of Participants Who Discontinue Study Drug Due to an AE 6. Laboratory Parameter (Hematology): Concentration of Hemoglobin on Days 21, 42, 63, 84, 105, and 126 7. Laboratory Parameter (Hematology): Hematocrit on Days 21, 42, 63, 84, 105, and 126 8. Laboratory Parameter (Hematology): RBC Count on Days 21, 42, 63, 84, 105, and 126 9. Laboratory Parameter (Hematology): Reticulocyte Count on Days 21, 42, 63, 84, 105, and 126 10. Laboratory Parameter (Hematology): Platelet Count on Days 21, 42, 63, 84, 105, and 126 11. Blood Pressure (BP) at Days 21, 42, 63, 84, 105 and 126 12. Titer of Anti-drug Antibody (ADA) to Sotatercept;Timepoint(s) of evaluation of this end point: 1. Predose Day 1, Day 7, Day 14, Predose Day 21, Day 22, Day 28, Day 35, Predose Days 42, 63, 84 and 105 2. Predose Day 1, Day 7, Day 14, Predose Day 21, Day 22, Day 28, Day 35, Predose Days 42, 63, 84 and 105 3. Predose Day 1, Day 7, Day 14, and Predose Day 21 4. Up to 24 weeks 5. Up to 24 weeks 6. Up to 24 weeks 7. Up to 24 weeks 8. Up to 24 weeks 9. Up to 24 weeks 10. Up to 24 weeks 11. Up to 24 weeks 12. Up to 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2) 2. Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) 3. Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP) 4. Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC) 5. Mean Change from Baseline in Eccentricity Index 6. Mean Change from Baseline in Right Ventricular (RV) Function (Cohort 1 and 2 Only) 7. Mean Change from Baseline on Cardiac Output (Cohort 1 and 2 Only) 8. Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohort 1 and 2 Only) 9. Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score 10. Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) 11. Percentage of Participants who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC) ;Timepoint(s) of evaluation of this end point: 1. Baseline and Week 24 2. Baseline and Week 24 3. Baseline and Week 24 4. Baseline and Week 24 5. Baseline and Week 24 6. Baseline and Week 24 7. Baseline and Week 24 8. Baseline and Week 24 9. Baseline and Week 24 10. Baseline and Week 24 11. Baseline and Week 24 | — |
Countries
Australia, Colombia, France, Germany, Israel, Mexico, Netherlands, Poland, South Africa, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactPaul Andrew Reyfman
Merck Sharp & Dohme LLC
Outcome results
None listed