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.
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
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 April 23, 2014