A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (ZENITH)
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|ClinicalTrials.gov Identifier: NCT04896008|
Recruitment Status : Recruiting
First Posted : May 21, 2021
Last Update Posted : March 31, 2022
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: Sotatercept Other: Placebo||Phase 3|
Study A011-14 is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate sotatercept when added to maximum tolerated background PAH therapy on time to first event of all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥ 24 hours, in participants with WHO FC IV PAH or WHO FC III PAH at high risk of mortality.
Participants with symptomatic PAH (WHO FC III or FC IV at high risk of mortality) who present with idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin-induced, post-shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defect. Participants must have a Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 risk score of ≥ 10 and be on maximum tolerated combination background PAH therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||166 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
Each eligible participant will be randomized in a 1:1 ratio to 1 of the following 2 treatment arms during the DBPC Treatment Period:
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official 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|
|Actual Study Start Date :||October 13, 2021|
|Estimated Primary Completion Date :||November 2025|
|Estimated Study Completion Date :||December 2026|
Placebo Comparator: Placebo plus background PAH therapy
Placebo administered subcutaneously (SC) every 21 days plus background PAH therapy
Experimental: Sotatercept plus background PAH therapy
Sotatercept at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, SC every 21 days plus background PAH therapy
Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1.
Other Name: ACE-011
- Time to first confirmed morbidity or mortality event. [ Time Frame: From randomization to first event, up to approximately 46 months. ]Events are defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥ 24 hours. All events will be adjudicated by a blinded, independent committee of clinical experts.
- Overall survival [ Time Frame: Through study completion, estimated up to 46 months ]Time from randomization to death from any cause.
- Transplant-free survival. [ Time Frame: Through study completion, estimated up to 46 months ]Time from randomization to lung transplantation or death from any cause.
- Proportion of participants who experienced a mortality event. [ Time Frame: Through study completion, estimated up to 46 months ]Death from any cause is tracked throughout the study.
- Change from baseline in REVEAL Lite 2 risk score. [ Time Frame: From screening to Week 24. ]REVEAL Lite 2 risk score in each participant was measured at Week 24 versus baseline.
- Proportion of participants achieving a low or intermediate (≤ 7) REVEAL Lite 2 risk score at Week 24. [ Time Frame: From screening to Week 24. ]REVEAL Lite 2 risk score in each participant was measured at Week 24.
- Change from baseline in NT-proBNP levels. [ Time Frame: From screening to Week 24. ]NT-proBNP was measured at baseline and Week 24.
- Change from baseline in mean pulmonary artery pressure (mPAP) at Week 24. [ Time Frame: From screening to Week 24. ]mPAP was measured by right heart catheterization (RHC) during screening and Week 24.
- Change from baseline in pulmonary vascular resistance (PVR). [ Time Frame: From screening to Week 24. ]PVR is a hemodynamic variable measured by RHC during screening and Week 24.
- Proportion of participants who improve in WHO FC. [ Time Frame: From randomization to the end of the double-blind, placebo-controlled (DBPC) treatment period (EOT). ]The severity of an individual's PAH symptoms was graded using the WHO FC system at baseline and at the end of treatment (EOT).
- Change from baseline in 6MWD. [ Time Frame: From randomization to Week 24. ]6-minute walk test is a clinical exercise test to assess the functional capacity. 6MWD at baseline and Week 24 were measured.
- Change from baseline in cardiac output (CO) at Week 24. [ Time Frame: From screening to Week 24. ]CO is a component of the PVR calculation, and reduced CO reflects increased risk of morbidity and mortality.
- Change from baseline in EuroQoL-5 dimensions scale 5 levels (EQ-5D-5L) index score at Week 24. [ Time Frame: From randomization to Week 24. ]EQ 5D 5L index score measures health-related quality of life states in adults. The EQ 5D 5L questionnaire is designed for self-completion and captures information directly from the respondent. EQ 5D 5L index scores at baseline and Week 24 were measured.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04896008
|Contact: Clinical Trial Manager||617-649-9200||Trialsites@merck.com|
|United States, Kansas|
|University of Kansas Medical Center||Recruiting|
|Kansas City, Kansas, United States, 66160|
|Contact: Luigi Boccardi 913-588-4022 email@example.com|
|Principal Investigator: Leslie Spikes, MD|
|United States, Michigan|
|University of Michigan||Not yet recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator: Vallerie McLaughlin, MD|
|United States, New York|
|University of Rochester||Recruiting|
|Rochester, New York, United States, 14642|
|Contact: Allison Light 585-273-4351 firstname.lastname@example.org|
|Contact: Andrew Mintz 585 273 4351 email@example.com|
|Principal Investigator: Daniel Lachant, MD|