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.

NCT01146574 | Completed Phase 2 Results DMC

• 1 other identifier: ACE-011-REN-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 24

Brief Summary

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

Conditions

Anemia

Keywords

End-Stage Renal Disease; Anemia; Hemodialysis; Renal Anemia; ESRD

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• The Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

  From first dose up to 115 days post last dose

• Number of Participants With Hemoglobin > 12g/dL

  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

  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

  From pre-dose up to the final visit 112 days after last dose (up to 225 days)

• Changes in Follicle Stimulating Hormone (FSH)

  Day 1 (baseline), Day 15, Day 29, and Day 113

Study Arms (5)

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

Biological: Sotatercept

0.3mg/kg Sotatercept

EXPERIMENTAL

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

Biological: Sotatercept

0.5mg/kg Sotatercept

EXPERIMENTAL

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

Biological: Sotatercept

0.7mg/kg Sotatercept

EXPERIMENTAL

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

Biological: Sotatercept

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

Sotatercept BIOLOGICAL

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

Also known as: ACE-011

0.1mg/kg Sotatercept; 0.3mg/kg Sotatercept; 0.5mg/kg Sotatercept; 0.7mg/kg Sotatercept

Placebo BIOLOGICAL

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead
• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: collaborator

Study Sites (24)

North American Research Institute

Azusa, California, 91702-3439, United States

Location

West Glendale Dialysis

Glendale, California, 91205, United States

Location

California Institute of Renal Research

La Mesa, California, 91942, United States

Location

Academic Medical Center

Los Angeles, California, 90022, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Nephrology Specialist Medical Group

Orange, California, 92868, United States

Location

Pines Clinical Research Inc.

Pembroke Pines, Florida, 33028, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Fresenius Medical Care North America MI

Kalamazoo, Michigan, 49007, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Nephrology and Hypertension Associates, LTD

Tupelo, Mississippi, 38801, United States

Location

St. Louis University Medical Center

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Kidney Specialists of Southen Nevada

Las Vegas, Nevada, 89106, United States

Location

Brookview Hill Research Associates, LLC

Winston-Salem, North Carolina, 27103, United States

Location

MetroHealth Medical Systems

Cleveland, Ohio, 44109, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

Nephrology Associates, PC

Nashville, Tennessee, 37205, United States

Location

Corva Kidney Center Webster

Houston, Texas, 77003, United States

Location

Beechnut Dialysis Center

Houston, Texas, 77036, United States

Location

Miracle Medical Clinic

Houston, Texas, 77055, United States

Location

Gessner Dialysis Center

Houston, Texas, 77074, United States

Location

Tyler Nephrology Associates, PC

Tyler, Texas, 75702, United States

Location

University of Virginia at University Ave.

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Anemia; Kidney Failure, Chronic

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trails@bms.com

Please email

Study Officials

• William T Smith, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2010
• First Posted: June 17, 2010
• Study Start: June 30, 2010
• Primary Completion: March 7, 2016
• Study Completion: March 7, 2016
• Last Updated: March 1, 2024
• Results First Posted: March 1, 2024

Record last verified: 2024-02

Locations

US (24)