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

June 16, 2010
April 3, 2014
August 2010
March 2015   (final data collection date for primary outcome measure)
  • 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)
  • Part 1: Single-dose pharmacokinetic endpoints (in serum and/or blood) [ Time Frame: Part 1: 113 days ] [ Designated as safety issue: No ]
  • Part 2: Proportion of subjects able to achieve an increase in Hb ≥ 1g/dL during any 4 week period [ Time Frame: Part 2: 197 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01146574 on ClinicalTrials.gov Archive Site
  • 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
  • • treatment emergent AEs [ Time Frame: Part 1: 113 days - Part 2: 197 days ] [ Designated as safety issue: Yes ]
  • • Proportion of subjects with Hb > 12g/dL [ Time Frame: Part 1: 113 days Part 2: 197 days ] [ Designated as safety issue: Yes ]
  • • Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period [ Time Frame: Part 1: 113 days Part 2: 197 days ] [ Designated as safety issue: Yes ]
  • • Frequency of clinically significant changes in laboratory parameters [ Time Frame: Part 1: 113 days Part 2: 197 days ] [ Designated as safety issue: Yes ]
  • • Serum levels of Vitamin D (vit D), 25-hydroxy vitamin D (25-OH-vit D), and 1,25-dihydroxy vitamin D (1,25-vit D) [ Time Frame: Part 1: 113 days Part 2: 197 days ] [ Designated as safety issue: Yes ]
  • • Blood pressure changes from baseline [ Time Frame: Part 1: 113 days Part 2: 197 days ] [ Designated as safety issue: Yes ]
  • • Changes in FSH and sex steroid concentrations and potential related AEs [ Time Frame: Part 1: 113 days Part 2: 197 days ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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)

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Anemia
  • 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
  • Biological: Placebo
    Placebo
  • 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
    Intervention: Biological: Sotatercept
  • Experimental: 0.3mg/kg Sotatercept
    Dose Group 1: 0.3 mg/kg sotatercept subcutaneous every 28 days
    Intervention: Biological: Sotatercept
  • Experimental: 0.5mg/kg Sotatercept
    Dose Group 2: 0.5 mg/kg sotatercept subcutaneous every 28 days
    Intervention: Biological: Sotatercept
  • Experimental: 0.7mg/kg Sotatercept
    Dose Group 3: 0.7 mg/kg sotatercept subcutaneous every 28 days
    Intervention: Biological: Sotatercept
  • Placebo Comparator: Placebo
    The Placebo to Sotatercept ratio is 1:3 meaning for every 1 patient that receives Placebo, 3 patients will receive Sotatercept.
    Intervention: Biological: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
43
May 2016
March 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Daniel Aversa 732-652-5671 daversa@celgene.com
Contact: Michael Weiswasser 732-652-6462 mweiswasser@celgene.com
United States
 
NCT01146574
ACE-011-REN-001
Yes
Celgene Corporation
Celgene Corporation
Acceleron Pharma, Inc.
Study Director: William T Smith, MD Celgene Corporation
Celgene Corporation
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP