Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01999582 | A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis | PHASE2 | COMPLETED | 50 | — | — | Nov 30, 2013 | Aug 31, 2016 | Jun 24, 2024 | 23 | Belgium, Germany +3 |
| NCT01146574 | A Phase 2a Study To Evaluate The Pharmacokinetics, Safety, Efficacy, Tolerability, And Pharmacodynamics of Sotatercept (ACE-011) for the Correction of Anemia in Subjects With End-stage Renal Disease on Hemodialysis. | PHASE2 | COMPLETED | 50 | — | — | Jun 30, 2010 | Mar 7, 2016 | Mar 1, 2024 | 24 | United States |
Area Under the plasma concentration-time curve over 14-day dosing interval (AUC14) for Sotatercept., The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Area under the plasma concentration-time curve over 28-day dosing interval (AUC28d). All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Maximum observed serum concentration (Cmax14d) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Maximum observed serum concentration (Cmax28d) of sotatercept, obtained directly from the observed concentration-time data combining the profiles following the first two doses. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Time to maximum serum concentration (Tmax) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Terminal elimination half-life (T1/2). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Lambda, apparent terminal rate constant (final dose only). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analysis of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Cmax is a pharmacokinetic parameter defined as the observed maximum concentration of the study drug in the serum and/or blood. Cmax will be estimated from the sotatercept concentration versus time data using noncompartmental method.
Time to observed maximum concentration (Tmax) is defined as the amount of time in days for a drug to reach the maximum concentration after administration.
AUC-28 days is defined as area under the concentration-time curve over the first 28-day dosing interval
Area under the concentration-time curve from time zero extrapolated to infinity. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.
Apparent Total Clearance (CL/F) is defined as the volume of plasma from which the study drug is completely removed per unit of time. It is equal to the drug dose divided by the area-under-the-curve.
Apparent volume of distribution based on terminal phase (Vz/F) is defined as the apparent volume in which the current amount of drug in the body must be dispersed in order to give the current plasma concentration. Apparent volume of distribution is important for determining the dose required to produce a desired plasma concentration of the drug.
Terminal plasma half-life (t1/2,z) is the time taken for concentration of the study drug to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma.
| Arm | Type | Description |
|---|---|---|
| Intravenous Dose Group 1, 2, and 3 | EXPERIMENTAL | Intravenous Dose Group 1 starting at 0.1 mg/kg and escalated in Dose Groups 2 (0.2 mg/kg) and Dose Group 3 (0.1, 0.2, 0.3, 0.4 mg/kg, titrated based on titration rules, administered every 14 days) |
| Subcutaneous Dose Group 1, 2, and 3 | EXPERIMENTAL | Subcutaneous Dose Group 1 starting at 0.13 mg/kg and escalated in Dose Groups 2 (0.26 mg/kg) and Dose Group 3 (0.4 to 0.5 mg/kg, titrated based on titration rules, administered every14 days) |
| 0.1mg/kg Sotatercept | EXPERIMENTAL | Approximately 8 subjects will be randomized to receive either a single 0.1 mg/kg subcutaneous dose of sotatercept or matching placebo in a 3:1 ratio |
| 0.3mg/kg Sotatercept | EXPERIMENTAL | Dose Group 1: 0.3 mg/kg sotatercept subcutaneous every 28 days |
| 0.5mg/kg Sotatercept | EXPERIMENTAL | Dose Group 2: 0.5 mg/kg sotatercept subcutaneous every 28 days |
| 0.7mg/kg Sotatercept | EXPERIMENTAL | Dose Group 3: 0.7 mg/kg sotatercept subcutaneous every 28 days |
| Placebo | PLACEBO_COMPARATOR | The Placebo to Sotatercept ratio is 1:3 meaning for every 1 patient that receives Placebo, 3 patients will receive Sotatercept. |
| Name | Type | Description |
|---|---|---|
| Sotatercept | BIOLOGICAL | Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group. |
| Placebo | BIOLOGICAL | Placebo |
Inclusion Criteria: 1. Males or females ≥ 18 years of age. 2. Subjects on at least 6 hours of hemodialysis per week, for at least 12 weeks before screening 3. Subjects must be on a stable intravenous or subcutaneous dose of Erythropoietin Stimulating Agents (excluding methoxy polyethylene glycol-ep...