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

  Show 28 Study Locations
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 July 23, 2014