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.

Celgene

Status and phase: Completed; Phase 2

Conditions: Anemia

Treatments: Biological: Sotatercept; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01146574

ACE-011-REN-001

Details and patient eligibility

About

This is the first study in hemodialysis subjects with anemia to evaluate the pharmacokinetics, safety, efficacy, tolerability, and pharmacodynamics of sotatercept (ACE-011)

Full description

Part 1:

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

Part 2:

Approximately 8 subjects will be randomized to each of the 3 sequential dose groups (0.3mg/kg or 0.5mg/kg or 0.7 mg/kg) with a 3:1 ratio of sotatercept or placebo (6 subjects in the sotatercept arm and 2 in the placebo arm). A total of 24-36 subjects may be randomized in the 3 dose groups.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or females ≥18 years of age.
• Subjects on hemodialysis for at least 12 weeks before screening
• Subjects on a stable dose of Erythrocyte Stimulating Agents product to maintain Hemoglobin (Hb) for at least 6 weeks prior to screening.
• 3 consecutive pre-dialysis Hb concentrations with a mean ≥10 to ≤ 12 g/dL (≥100 to ≤120 g/L) at screening and one pre-dialysis Hb concentration ≥8 to < 10 g/dL (≥ 80 to < 100 g/L) before randomization.
• Adequate iron status defined as serum transferrin saturation ≥ 20% before randomization.

Exclusion criteria

• Non renal causes of anemia.
• Subjects on peritoneal dialysis.
• Systemic hematological disease
• High sensitivity C-reactive protein >50mg/L at screening.
• Alanine transaminase (ALT) or aspartate transaminase (AST) laboratory values > 2 times the upper limit of normal (ULN) at screening.
• Uncontrolled diabetes mellitus (HbA1c > 9) at screening.
• Uncontrolled hypertension.
• Red Blood Count (RBC) transfusions within 8 weeks prior to screening.
• Active serious infection or history of recurrent serious infection likely to recur during the study
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product or to the iron products needed to normalize iron levels for subjects.
• Subjects that received treatment with another investigational drug or device within 28 days prior to Day 1
• Pregnant or lactating females.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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50 participants in 5 patient groups, including a placebo group

0.1mg/kg Sotatercept

Experimental group

Description:

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

Treatment:

Biological: Sotatercept

0.3mg/kg Sotatercept

Experimental group

Description:

Dose Group 1: 0.3 mg/kg sotatercept subcutaneous every 28 days

Treatment:

Biological: Sotatercept

0.5mg/kg Sotatercept

Experimental group

Description:

Dose Group 2: 0.5 mg/kg sotatercept subcutaneous every 28 days

Treatment:

Biological: Sotatercept

0.7mg/kg Sotatercept

Experimental group

Description:

Dose Group 3: 0.7 mg/kg sotatercept subcutaneous every 28 days

Treatment:

Biological: Sotatercept

Placebo

Placebo Comparator group

Description:

The Placebo to Sotatercept ratio is 1:3 meaning for every 1 patient that receives Placebo, 3 patients will receive Sotatercept.

Treatment:

Biological: Placebo