A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis

Study Overview
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Brief Summary
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To determine the optimal route of administration, dose level, and safety of intravenous and subcutaneous dosing of sotatercept for maintaining hemoglobin levels in subjects who are on hemodialysis.

Official Title
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A Phase 2 Multicenter, Randomized, Open-Label , Multiple-Dose Study of Intravenous and Subcutaneous Administration of Sotatercept (ACE-011) in Subjects With End-Stage Kidney Disease on Hemodialysis Switched From Erythropoeisis Stimulating Agents With Staggered Dose Group Escalation in Part 1 Followed by a Parallel Group, Active Controlled Study of Selected Dose(s) and Regimen(s) in Part 2: To Evaluate the Pharmacokinetics, Safety, Tolerability, Efficacy, Dosing Regimen, and Pharmacodynamics of Sotatercept

Conditions
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Anemia, Kidney Failure, Chronic

Intervention / Treatment
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* Biological: Sotatercept
* Biological: Sotatercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 18 years of age. Subjects on at least 6 hours of hemodialysis per week, for at least 12 weeks before screening Subjects must be on a stable intravenous or subcutaneous dose of Erythropoietin Stimulating Agents (excluding methoxy polyethylene glycol-epoetin beta [Mircera]) to maintain hemoglobin. A mean predialysis hemoglobin concentration ≥ 10 g/dL (grams per deciliter) to ≤ 12 g/dL (≥ 100 g/L (grams per liter) to ≤ 120 g/L) obtained from three consecutive days. 4. A Body Mass Index value ≥ 18.5 kg/m2 (kilograms per m2) at screening. 5. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. 6. Able to adhere to the study visit schedule and comply with all protocol requirements. Exclusion Criteria: Non renal causes of anemia Subjects on peritoneal dialysis. Systemic hematological disease Uncontrolled diabetes mellitus (HbA1c (hemoglobin A1c) > 9%) at screening. Uncontrolled hypertension defined as mean of home systolic blood pressure > 160 mm Hg (millimeter of mercury) or mean of home diastolic blood pressure > 90 mm Hg calculated once during the screening period prior to randomization Subjects with heart failure History of malignancy (except excised and cured non-melanoma skin cancer, or cervical carcinoma in situ that was surgically ablated more than 5 years ago). Anticipated or scheduled living donor renal transplant during the course of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Dose Group 1, 2, and 3<br>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) | Biological: Sotatercept<br>* Sotatercept is dosed intravenously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.<br>* Other names: ACE-011;|
| Experimental: Subcutaneous Dose Group 1, 2, and 3<br>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) | Biological: Sotatercept<br>* Sotatercept is dosed subcutaneously every 14 days. The dose a subject receives will depend on the randomization arm and the dose group.<br>* Other names: ACE-011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (Cmax) | Maximum observed concentration in serum | 28 days | 
| Pharmacokinetics (Tmax) | Time to maximum concentration | 28 days | 
| Pharmacokinetics (AUC 28d) | Area under the concentration-time curve | 28 days | 
| Pharmacokinetics (t1/2,z) | Terminal half life | 211 days | 
| Adverse Event | treatment emergent adverse sevents (TEAEs) and number of subjects with TEAEs. | 211 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Change in mean hemoglobin concentration between baseline and day 113 | 113 days | 
| Bone Turnover | Change in serum bone biomarker concentrations between baseline and end of study (day 211) | 211 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, End Stage Kidney Disease, Chronic Kidney Disease, Dialysis, Erythrpoietin Stimulating Agent (ESA)