Trial · NCT04896008
A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)
NCT04896008, Phase 3, Completed, Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA; results first posted 2025-08-22
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH). Trials, record NCT04896008. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04896008
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)
- NCT number
- NCT04896008
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 173 participants, actual
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Sotatercept, Placebo
- First posted
- 2021-05-21
- Last updated
- 2026-05-29
- Other registries' IDs
- eudract:2021-001498-21
- Results first posted
- 2025-08-22
Source ClinicalTrials.gov
Registered outcomes13
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Time to First Confirmed Morbidity or Mortality Event | Up to approximately 31 months | Morbidity or mortality events were defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥24 hours. All events were adjudicated by a blinded, independent committee of clinical experts. Only adjudication-confirmed lung transplantation and PAH worsening-related hospitalization of ≥24 hours were included in the primary analysis. All deaths that are a first event for a participant were included regardless of adjudication. The time from randomization to the first confirmed morbidity or mortality event, calculated using the non-parametric Kaplan-Meier method, is presented. |
| Secondary | Overall Survival (OS) | Up to approximately 31 months | OS was defined as the time from randomization to death due to any cause. As pre-specified in the SAP, all deaths up to data cutoff, including among participants who completed or discontinued the study, were included except for those that occurred after enrollment in the long-term follow-up study (MK-7962-004) or after lung transplantation. The OS for participants, calculated using the non-parametric Kaplan-Meier method, is reported. |
| Secondary | Transplant-free Survival | Up to approximately 31 months | Transplant-free survival was defined as the time from randomization to the first lung transplantation or death due to any cause. As pre-specified in the SAP, all deaths up to data cutoff, including among participants who completed or discontinued the study, were included except for those that occurred after enrollment in the long-term follow-up study (MK-7962-004) or after lung transplantation. Transplant-free survival for participants, calculated using the non-parametric Kaplan-Meier method, is reported. |
| Secondary | Percentage of Participants Who Experienced a Mortality Event | Up to approximately 31 months | Mortality events were defined as death due to any cause throughout the study. As pre-specified in the SAP, all deaths up to data cutoff, including among participants who completed or discontinued the study, were included except for those that occurred after enrollment in the long-term follow-up study (MK-7962-004) or after lung transplantation. The percent of participants who experienced a mortality event is reported. |
| Secondary | Change From Baseline in REVEAL Lite 2.0 Risk Score at Week 24 | Baseline and Week 24 | REVEAL Lite 2.0 risk scoring is used to guide PAH treatment decisions. Total score uses 6 variables with each assessed based on contribution to mortality risk. Variables and sub-score ranges: eGFR (0, +1), WHO FC (-1, 0, +1, +2), SBP (0, +1), heart rate (0, +1), 6MWD (-2, -1, 0, +1), and NT-proBNP (-2, 0, +2). Sub-scores are added to a base score of +6 and a total score of 1 to 14 is obtained (≤5=low risk; 6,7=intermediate risk; ≥8=high risk). A higher score = higher risk. Median change and full ranges are reported based on observed data. |
| Secondary | Percentage of Participants Achieving a Low or Intermediate (≤7) REVEAL Lite 2 Risk Score at Week 24 | Week 24 | REVEAL Lite 2.0 risk scoring is used to guide PAH treatment decisions. Total score uses 6 variables with each assessed based on contribution to mortality risk. Variables and sub-score ranges: eGFR (0, +1), WHO FC (-1, 0, +1, +2), SBP (0, +1), heart rate (0, +1), 6MWD (-2, -1, 0, +1), and NT-proBNP (-2, 0, +2). Sub-scores are added to a base score of +6 and a total score of 1 to 14 is obtained (≤5=low risk; 6,7=intermediate risk; ≥8=high risk). A higher score = higher risk. Per SAP, participants who did not have a REVEAL risk score at Week 24 were considered as non-responders and multiple imputation was not conducted for this endpoint. Comparisons between this analysis reporting non-imputed data should not be made to other REVEAL analyses which included imputation of missing Week 24 data. The percentage of participants who achieved a low or intermediate REVEAL Lite 2.0 score at Week 24 is reported. |
| Secondary | Change From Baseline in NT-proBNP Levels at Week 24 | Baseline and Week 24 | NT-proBNP is secreted by cardiomyocytes in response to ventricular stretch and is an established noninvasive marker of ventricular dysfunction in patients with PAH. Blood samples were collected at baseline and at Week 24 to measure NT-proBNP levels. Median change and full ranges are reported based on observed data. |
| Secondary | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 24 | Baseline and Week 24 | mPAP is a hemodynamic variable associated with PAH severity and was measured measured at baseline and at Week 24 by right heart catheterization (RHC). Median change and full ranges are reported based on observed data. |
| Secondary | Change From Baseline in Pulmonary Vascular Resistance (PVR) | Baseline and Week 24 | PVR is a hemodynamic variable associated with PAH severity and was measured at baseline and at Week 24 by right heart catheterization (RHC). Median change and full ranges are reported based on observed data. |
| Secondary | Percentage of Participants Who Improve in WHO FC | Baseline and up to approximately 31 months | The severity of a participant's PAH symptoms was graded using the WHO FC system. WHO functional classification for PAH ranges 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). Participants who improve in WHO FC were classified into "Improved", "No change", or "Worsened" (Improved = reduction in FC; Worsened = increase in FC; No change = no change in FC). The percentage of participants who had improvement from baseline in WHO FC at the end of the treatment period is reported. |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 registered outcomesOutcomes13
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Time to First Confirmed Morbidity or Mortality Event | Up to approximately 31 months | All randomized participants who received at least one dose of study treatment. | Months | MEDIAN |
| SECONDARY | Overall Survival (OS) | Up to approximately 31 months | All randomized participants who received at least one dose of study treatment. | Months | MEDIAN |
| SECONDARY | Transplant-free Survival | Up to approximately 31 months | All randomized participants who received at least one dose of study treatment. | Months | MEDIAN |
| SECONDARY | Percentage of Participants Who Experienced a Mortality Event | Up to approximately 31 months | All randomized participants who received at least one dose of study treatment. | Percentage of Participants | NUMBER |
| SECONDARY | Change From Baseline in REVEAL Lite 2.0 Risk Score at Week 24 | Baseline and Week 24 | All randomized participants who received at least one dose of study treatment and who had REVEAL Lite 2.0 Risk Score available at both baseline and Week 24. | Scores on a scale | MEDIAN |
| SECONDARY | Percentage of Participants Achieving a Low or Intermediate (≤7) REVEAL Lite 2 Risk Score at Week 24 | Week 24 | All randomized participants who received at least one dose of study treatment, who were randomized more than 24 weeks prior to the data cutoff, and who had a REVEAL Lite 2.0 risk score \>7 at baseline. | Percentage of Participants | NUMBER |
| SECONDARY | Change From Baseline in NT-proBNP Levels at Week 24 | Baseline and Week 24 | All randomized participants who received at least one dose of study treatment and who had NT-proBNP levels available at both baseline and Week 24. | pg/mL | MEDIAN |
| SECONDARY | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 24 | Baseline and Week 24 | All randomized participants who received at least one dose of study treatment and who had mPAP available at both baseline and Week 24. | mmHg | MEDIAN |
| SECONDARY | Change From Baseline in Pulmonary Vascular Resistance (PVR) | Baseline and Week 24 | All randomized participants who received at least one dose of study treatment and who had PVR available at both baseline and Week 24. | Dynes*sec/cm^5 | MEDIAN |
| SECONDARY | Percentage of Participants Who Improve in WHO FC | Baseline and up to approximately 31 months | All randomized participants who received at least one dose of study treatment. | Percentage of Participants | NUMBER |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 outcomesResults by group26
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Time to First Confirmed Morbidity or Mortality Event | Sotatercept | NA | 95% Confidence Interval 25.4 to NA | Months | |
| Time to First Confirmed Morbidity or Mortality Event | Placebo | 9.6 | 95% Confidence Interval 5.9 to 14.8 | Months | |
| Overall Survival (OS) | Sotatercept | NA | 95% Confidence Interval 25.4 to NA | Months | |
| Overall Survival (OS) | Placebo | NA | 95% Confidence Interval NA to NA | Months | |
| Transplant-free Survival | Sotatercept | NA | 95% Confidence Interval 25.4 to NA | Months | |
| Transplant-free Survival | Placebo | NA | 95% Confidence Interval NA to NA | Months | |
| Percentage of Participants Who Experienced a Mortality Event | Sotatercept | 12.8 | Percentage of Participants | ||
| Percentage of Participants Who Experienced a Mortality Event | Placebo | 16.3 | Percentage of Participants | ||
| Change From Baseline in REVEAL Lite 2.0 Risk Score at Week 24 | Sotatercept | -3.0 | Full Range -9.0 to 2.0 | Scores on a scale | |
| Change From Baseline in REVEAL Lite 2.0 Risk Score at Week 24 | Placebo | -1.0 | Full Range -6.0 to 5.0 | Scores on a scale |
1 to 10 of 26Source ClinicalTrials.gov
See all 26 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Sotatercept | 86 | |
| Overall Study | STARTED | Placebo | 86 | |
| Overall Study | COMPLETED | Sotatercept | 69 | |
| Overall Study | COMPLETED | Placebo | 60 | |
| Overall Study | NOT COMPLETED | Sotatercept | 17 | |
| Overall Study | NOT COMPLETED | Placebo | 26 |
Source ClinicalTrials.gov
Adverse events372
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Sotatercept | 10 | 86 | 11 |
| other | Anaemia | Blood and lymphatic system disorders | Placebo | 6 | 86 | 7 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Sotatercept | 11 | 86 | 14 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Placebo | 8 | 86 | 10 |
| other | Atrial fibrillation | Cardiac disorders | Sotatercept | 5 | 86 | 6 |
| other | Atrial fibrillation | Cardiac disorders | Placebo | 2 | 86 | 2 |
| other | Palpitations | Cardiac disorders | Sotatercept | 10 | 86 | 13 |
| other | Palpitations | Cardiac disorders | Placebo | 5 | 86 | 5 |
| other | Vertigo | Ear and labyrinth disorders | Sotatercept | 5 | 86 | 6 |
| other | Vertigo | Ear and labyrinth disorders | Placebo | 2 | 86 | 2 |
1 to 10 of 372Source ClinicalTrials.gov
See all 372 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Sotatercept | 13 | 86 |
| Total, all-cause mortality | Placebo | 20 | 86 |
| Total, other adverse events | Sotatercept | 82 | 86 |
| Total, other adverse events | Placebo | 77 | 86 |
| Total, serious adverse events | Sotatercept | 52 | 86 |
| Total, serious adverse events | Placebo | 64 | 86 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 40167274 | RESULT |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Sotatercept vs Placebo: deaths from any cause | Trial comparisons |
| Sotatercept vs Placebo: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT04896008
GET https://conductscience.org/api/trials/v1/NCT04896008/results?page=2