A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)

• Register: ClinicalTrials.gov
• Last refreshed on: 31 March 2025
• Main ID: NCT04896008
• Date of registration: 13/05/2021
• Prospective Registration: Yes
• Primary sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Public title: A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH) ZENITH
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Sotatercept When Added to Maximum Tolerated Background Therapy in Participants With Pulmonary Arterial Hypertension (PAH) World Health Organization (WHO) Functional Class (FC) III or FC IV at High Risk Mortality
• Date of first enrolment: December 1, 2021
• Target sample size: 172
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04896008
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Israel, Italy, Mexico, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- Documented diagnostic right heart catheterization prior to screening confirming the
diagnosis of World Health Organization (WHO) pulmonary arterial hypertension (PAH)
Group 1 in any of the following subtypes:

- Idiopathic PAH

- Heritable PAH

- Drug/toxin-induced PAH

- PAH associated with connective tissue diseases (CTD)

- PAH associated with simple, congenital systemic to pulmonary shunts at least 1
year following repair

- Symptomatic PAH classified as WHO functional class (FC) III or IV

- Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0
risk score of =9

- Right heart catheterization performed during screening (or within 2 weeks prior to
screening, if done at the clinical study site) documenting a minimum pulmonary
vascular resistance (PVR) of =5 Wood units and a pulmonary capillary wedge pressure
(PCWP) or left ventricular end-diastolic pressure (LVEDP) of =15 mmHg

- Clinically stable and on stable doses of maximum tolerated (per investigator's
judgment) double or triple background PAH therapies for at least 30 days prior to
screening

- Females of childbearing potential must:

- Have 2 negative urine or serum pregnancy tests as verified by the investigator
prior to starting study therapy; must agree to ongoing urine or serum pregnancy
testing during the course of the study and until 8 weeks after the last dose of
the study drug

- If sexually active with a male partner, have used, and agree to use highly
effective contraception without interruption per protocol; 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
treatment

- 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 treatment

- Male participants must:

- Agree to use a condom, defined as a male latex condom or nonlatex 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 treatment

- Ability to adhere to study visit schedule and understand and comply with all
protocol requirements

- Ability to understand and provide written informed consent

Exclusion Criteria:

- Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5

- Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency
virus-associated PAH and PAH associated with portal hypertension

- Diagnosis of pulmonary veno-occlusive diseases or pulmonary capillary
hemangiomatosis or overt signs of capillary and/or venous involvement

- Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local
laboratory test

- Baseline platelet count <50,000/mm3 (<50.0 x 109/L) at screening

- Baseline systolic blood pressure <85 mmHg at screening

- Pregnant or breastfeeding women

- Serum alanine aminotransferase or aspartate aminotransferase levels or total
bilirubin >3.0×ULN

- Currently enrolled in or have completed any other investigational product study
within 30 days for small molecule drugs or within 5 half-lives for biologics prior
to the date of signed informed consent

- Prior exposure to sotatercept or known allergic reaction to sotatercept, its
excipients or luspatercept

- History of pneumonectomy

- Untreated more than mild obstructive sleep apnea

- History of known pericardial constriction

- History of restrictive or congestive cardiomyopathy

- Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) >500 ms
during the screening period

- Personal or family history of long QT syndrome or sudden cardiac death

- Left ventricular ejection fraction <45% on historical echocardiogram within 1 year
prior to the screening visit

- Any current or prior history of symptomatic coronary disease (prior myocardial
infarction, percutaneous coronary intervention, coronary artery bypass graft
surgery, or cardiac anginal chest pain) in the past 6 months prior to the screening
visit

- Cerebrovascular accident within 3 months prior to the screening visit

- Significant (= 2+ regurgitation) mitral regurgitation or aortic regurgitation
valvular disease

- Currently on dialysis or anticipated need for dialysis within the next 12 months


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Other: Placebo

Drug: Sotatercept

Primary Outcome(s)

Time to First Confirmed Morbidity or Mortality Event [Time Frame: Up to approximately 31 months]

Secondary Outcome(s)

Change From Baseline in Cardiac Output (CO) at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Pulmonary Vascular Resistance (PVR) [Time Frame: Baseline and Week 24]

Percentage of Participants Who Improve in WHO FC [Time Frame: Up to approximately 31 months]

Overall survival (OS) [Time Frame: Up to approximately 31 months]

Transplant-Free Survival [Time Frame: Up to approximately 31 months]

Change From Baseline in EuroQoL-5 Dimensions Scale 5 Levels (EQ-5D-5L) Index Score at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in REVEAL Lite 2 Risk Score at Week 24 [Time Frame: Baseline and Week 24]

Percentage of Participants Who Experienced a Mortality Event [Time Frame: Up to approximately 31 months]

Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in 6-MWD at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in NT-proBNP levels at Week 24 [Time Frame: Baseline and Week 24]

Percentage of Participants Achieving a Low or Intermediate (=7) REVEAL Lite 2 Risk Score at Week 24 [Time Frame: Week 24]

Secondary ID(s)

A011-14

2021-001498-21

2023-509140-10

U1111-1309-6376

7962-006

MK-7962-006

Source(s) of Monetary Support

Please refer to primary and secondary sponsors