Sotatercept in Children with Pulmonary Artery Hypertension on Standard of Care

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

5 May 2023 → ongoing

Decision date (initial)

2023-12-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504861-22-00

EudraCT number

2022-000478-25

WHO UTN

U1111-1290-2858

ClinicalTrials.gov

NCT05587712

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Therapy, Pharmacokinetic

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 objectives 1

1. To evaluate the pharmacodynamics of sotatercept over 24 weeks of treatment

Conditions and MedDRA coding

Pulmonary arterial hypertension

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002756-PIP01-19

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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.
2. 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])
3. 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: o 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.
4. 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
5. 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
6. 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 14

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, or atrial septostomy
4. Unrepaired or residual cardiac shunt
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 12

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
7. Laboratory Parameter (Hematology): Hematocrit
8. Laboratory Parameter (Hematology): RBC Count
9. Laboratory Parameter (Hematology): Reticulocyte Count
10. Laboratory Parameter (Hematology): Platelet Count
11. Blood Pressure (BP)
12. Titer of Anti-drug Antibody (ADA) to Sotatercept

Secondary endpoints 11

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 (Cohorts 1 and 2)
7. Mean Change from Baseline on Cardiac Output (Cohorts 1 and 2)
8. Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohorts 1 and 2)
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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Paul Reyfman

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Paul Reyfman

Third parties 16

Locations

5 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 103 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications