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.

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Celgene Corporation
Sponsor:
Collaborator:
Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01146574
First received: June 16, 2010
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Anemia
Biological: Sotatercept
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • PK-Observed maximum Concentration (Cmax) [ Time Frame: Up to 309 days ] [ Designated as safety issue: No ]
    PK-Observed maximum Concentration (Cmax)

  • PK-Time to maximum concentration (Tmax) [ Time Frame: Up to 309 days ] [ Designated as safety issue: No ]
    PK-Time to maximum concentration (Tmax)

  • PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d) [ Time Frame: Up to 309 days ] [ Designated as safety issue: No ]
    PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d)

  • PK-Terminal half-life (T1/2,z) [ Time Frame: Up to 309 days ] [ Designated as safety issue: No ]
    PK-Terminal half-life (T1/2,z)


Secondary Outcome Measures:
  • Number of participants with Adverse Events [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Number of participants with Adverse Events

  • Proportion of subjects with Hb > 12g/dL [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Proportion of subjects with Hb > 12g/dL

  • Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period

  • Frequency of clinically significant changes in laboratory parameters from baseline [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Frequency of clinically significant changes in laboratory parameters from baseline

  • Blood pressure changes from baseline [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Blood pressure changes from baseline

  • Proportion of subjects that are able to achieve an absolute Hb concentration of > 10 g/dL [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Proportion of subjects that are able to achieve an absolute Hb concentration of > 10 g/dL

  • Time to reach target Hb concentration (> 10 g/dL) and target increase in Hb (≥ 1g/dL) [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Time to reach target Hb concentration (> 10 g/dL) and target increase in Hb (≥ 1g/dL)

  • Proportion of subjects rescued and length of time to rescue therapy [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Proportion of subjects rescued and length of time to rescue therapy

  • Changes in Follicle Stimulating Hormone (FSH) and Sex Steroid Concentrations [ Time Frame: Up to 309 days ] [ Designated as safety issue: Yes ]
    Changes in Follicle Stimulating Hormone and Sex Steroid Concentrations


Estimated Enrollment: 43
Study Start Date: August 2010
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01146574

Contacts
Contact: Daniel Aversa 732-652-5671 daversa@celgene.com
Contact: Michael Weiswasser 732-652-6462 mweiswasser@celgene.com

  Hide Study Locations
Locations
United States, California
North America Research Institute Withdrawn
Azusa, California, United States, 91702
California Renal Research Network Not yet recruiting
Glendale, California, United States, 91204
California Institute of Renal Research Recruiting
La Mesa, California, United States, 91942
Academic Medical Research Institute Recruiting
Los Angeles, California, United States, 90022
Monterery Park Dialysis Center Recruiting
Monterey Park, California, United States, 91754
Nephrology Specialist Medical Group Recruiting
Orange, California, United States, 92868
American Institute of Research Withdrawn
Whittier, California, United States, 90603
United States, District of Columbia
The George Washington Medical Faculty Associates Withdrawn
Washington, District of Columbia, United States, 20037
United States, Florida
Nephrology Associates of Central Florida Not yet recruiting
Orlando, Florida, United States, 32804
Pines Clinical Research Inc Recruiting
Pembroke Pines, Florida, United States, 33028
United States, Kentucky
University of Kentucky Medical Center Recruiting
Lexington, Kentucky, United States, 40536
United States, Michigan
Fresenius Medical Care North America Completed
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
DCR (DaVita Clinical Research) Completed
Minneapolis, Minnesota, United States, 55404
United States, Mississippi
Fresenius Medical Care North America Recruiting
Tupelo, Mississippi, United States, 38801
United States, Missouri
St. Louis University Medical Center-Division of Nephrology (9-FDT) Recruiting
St. Louis, Missouri, United States, 63110
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
United States, Nevada
Kidney Specialists of Southern Nevada Recruiting
Las Vegas, Nevada, United States, 89106
United States, North Carolina
Brookview Hills Research Associates, LLC Recruiting
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
MetroHealth Medical Systems Withdrawn
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
Northeast Clinical Research, LLC Recruiting
Bethlehem, Pennsylvania, United States, 18107
United States, Tennessee
Nephrology Associates, PC Recruiting
Nashville, Tennessee, United States, 37205
United States, Texas
Diagnostic Clinic of Houston Withdrawn
Houston, Texas, United States, 77003
Beechnut Dialysis Center Recruiting
Houston, Texas, United States, 77036
Gessner Dialysis and Kidney Center Recruiting
Houston, Texas, United States, 77074
Miracle Medical Clinic Recruiting
Houston, Texas, United States, 77055
San Antonio Kidney Disease Withdrawn
San Antonio, Texas, United States, 78229
Fresenius Medical Care Recruiting
Tyler, Texas, United States, 75702
United States, Virginia
University of Virginia - Nephrology Clinical Research Center Recruiting
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Celgene Corporation
Acceleron Pharma, Inc.
Investigators
Study Director: William T Smith, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01146574     History of Changes
Other Study ID Numbers: ACE-011-REN-001
Study First Received: June 16, 2010
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Celgene Corporation:
End-Stage Renal Disease
Anemia
Hemodialysis
Renal Anemia
ESRD

Additional relevant MeSH terms:
Anemia
Kidney Diseases
Kidney Failure, Chronic
Hematologic Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on September 22, 2014