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.

A Phase 2a, Multi-center, Randomized, Single Dose, Double-blind, Placebo-controlled Followed by a Multiple-dose, Single-blind, Placebo-controlled, Dose Escalation 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 (ESRD) on Hemodialysis (HD).

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

Study Overview

• Status: Completed
• Conditions: Anemia
• Intervention / Treatment: Biological: Placebo; Biological: Sotatercept

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Azusa, California, United States, 91702-3439
      • North American Research Institute
    • Glendale, California, United States, 91205
      • West Glendale Dialysis
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90022
      • Academic Medical Center
    • Orange, California, United States, 92868
      • Nephrology Specialist Medical Group
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research Inc.
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Fresenius Medical Care North America MI
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Nephrology and Hypertension Associates, LTD
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Kidney Specialists of Southen Nevada
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hill Research Associates, LLC
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Systems
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates, PC
  • Texas
    • Houston, Texas, United States, 77003
      • Corva Kidney Center Webster
    • Houston, Texas, United States, 77036
      • Beechnut Dialysis Center
    • Houston, Texas, United States, 77055
      • Miracle Medical Clinic
    • Houston, Texas, United States, 77074
      • Gessner Dialysis Center
    • Tyler, Texas, United States, 75702
      • Tyler Nephrology Associates, PC
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia at University Ave.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.1mg/kg Sotatercept; 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	Biological: Sotatercept; Part 1: Sotatercept single dose 0.1mg/kg subcutaneous Part 2: Sotatercept starting dose groups of 0.3mg/kg, 0.5mg/kg or 0.7 mg/kg in a sequential design, dosed subcutaneously every 28 days for up to 8 doses; Other Names: ACE-011
Experimental: 0.3mg/kg Sotatercept; Dose Group 1: 0.3 mg/kg sotatercept subcutaneous every 28 days	Biological: Sotatercept; Part 1: Sotatercept single dose 0.1mg/kg subcutaneous Part 2: Sotatercept starting dose groups of 0.3mg/kg, 0.5mg/kg or 0.7 mg/kg in a sequential design, dosed subcutaneously every 28 days for up to 8 doses; Other Names: ACE-011
Experimental: 0.5mg/kg Sotatercept; Dose Group 2: 0.5 mg/kg sotatercept subcutaneous every 28 days	Biological: Sotatercept; Part 1: Sotatercept single dose 0.1mg/kg subcutaneous Part 2: Sotatercept starting dose groups of 0.3mg/kg, 0.5mg/kg or 0.7 mg/kg in a sequential design, dosed subcutaneously every 28 days for up to 8 doses; Other Names: ACE-011
Experimental: 0.7mg/kg Sotatercept; Dose Group 3: 0.7 mg/kg sotatercept subcutaneous every 28 days	Biological: Sotatercept; Part 1: Sotatercept single dose 0.1mg/kg subcutaneous Part 2: Sotatercept starting dose groups of 0.3mg/kg, 0.5mg/kg or 0.7 mg/kg in a sequential design, dosed subcutaneously every 28 days for up to 8 doses; Other Names: ACE-011
Placebo Comparator: Placebo; The Placebo to Sotatercept ratio is 1:3 meaning for every 1 patient that receives Placebo, 3 patients will receive Sotatercept.	Biological: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Maximum Concentration (Cmax)	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.	From first dose up to Day 28
Time to Maximum Concentration (Tmax)	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.	From first dose up to Day 28
Area Under Curve (AUC)-28 Days	AUC-28 days is defined as area under the concentration-time curve over the first 28-day dosing interval	From first dose up to Day 28
AUCinf: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity	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.	From first dose up to Day 28
Apparent Total Clearance (CL/F)	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.	From first dose up to Day 28
Apparent Volume of Distribution Based on Terminal Phase (Vz/F)	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.	From first dose up to Day 28
Terminal Half-Life (t1/2,z)	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.	Days 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 85 and 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose up to 115 days post last dose
Number of Participants With Hemoglobin > 12g/dL	Number of participants with hemoglobin > 12g/dL including Hb values obtained after first study drug dose and before any rescue.	Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
Proportion of Participants With Rise in Hemoglobin > 2 g/dL During 4 Week Period	Proportion of participants with rise in hemoglobin (Hb) > 2 g/dL during a 4-week period including Hb values obtained after first study drug dose and before any rescue.	Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
Blood Pressure Changes From Baseline	Blood pressure was generally recorded on the day of dialysis and represent pre-dialysis values. Baseline is defined as blood pressure measurements recorded on Day 1 of the first dose administered.	From pre-dose up to the final visit 112 days after last dose (up to 225 days)
Changes in Follicle Stimulating Hormone (FSH)	The change in follicle stimulating measured at pre-specified timepoints throughout the treatment period.	Day 1 (baseline), Day 15, Day 29, and Day 113
Number of Participants With Hemoglobin > 10g/dL	Number of participants with hemoglobin > 10g/dL including Hb values obtained after first study drug dose and before any rescue. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
Number of Participants With Change From Baseline Hemoglobin ≥ 1g/dL	Number of participants with a change from in hemoglobin values ≥ 1g/dL including Hb values obtained after first study drug dose and before any rescue. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
Number of Participants With Hemoglobin > 10g/dL and Change From Baseline Hemoglobin ≥ 1g/dL	Number of participants with Hemoglobin > 10g/dL and a change from in hemoglobin values ≥ 1g/dL including Hb values obtained after first study drug dose and before any rescue. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
Length of Time to Rescue Therapy	The length of time in days that participants who were rescued received treatment. When applicable, participants were rescued for anemia. During the rescue, participants discontinued sotatercept and were unblinded to the study treatment. Participants who were rescued continued in the treatment phase of 200 days and a follow-up phase of 112 days after the treatment phase. Rescue is defined as the need for a blood transfusion or Erythropoiesis-stimulating agent (ESA) therapy.	From first dose up to blood transfusion or ESA therapy, up to approximately 209 days
Change From Baseline in Hemoglobin Values	Dose Cycle 1 is defined as the first 28 days of treatment for Dose Groups 0.3 mg/kg, 0.5 mg/kg, and 0.7 mg/kg and the first 14 days of treatment for Dose Group 0.7/0.4 mg/kg. End of the Treatment Period is defined as the day before the follow-up phase started. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	From first dose up to Day 225

Collaborators and Investigators

• Sponsor: Celgene
• Collaborators: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Investigators: Study Director: William T Smith, MD, Celgene Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2010
• Primary Completion (Actual): March 7, 2016
• Study Completion (Actual): March 7, 2016

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (Estimated): June 17, 2010

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Anemia; ESRD; Hemodialysis; End-Stage Renal Disease; Renal Anemia
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Anemia
• Other Study ID Numbers: ACE-011-REN-001