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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.

Primary Purpose

Anemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sotatercept
Placebo
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia focused on measuring End-Stage Renal Disease, Anemia, Hemodialysis, Renal Anemia, ESRD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • North American Research Institute
  • West Glendale Dialysis
  • California Institute of Renal Research
  • Academic Medical Center
  • Academic Medical Research Institute
  • Nephrology Specialist Medical Group
  • Pines Clinical Research Inc.
  • University of Kentucky
  • Fresenius Medical Care North America MI
  • DaVita Clinical Research
  • Nephrology and Hypertension Associates, LTD
  • St. Louis University Medical Center
  • Washington University School of Medicine
  • Kidney Specialists of Southen Nevada
  • Brookview Hill Research Associates, LLC
  • MetroHealth Medical Systems
  • Northeast Clinical Research Center
  • Nephrology Associates, PC
  • Corva Kidney Center Webster
  • Beechnut Dialysis Center
  • Miracle Medical Clinic
  • Gessner Dialysis Center
  • Tyler Nephrology Associates, PC
  • University of Virginia at University Ave.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

0.1mg/kg Sotatercept

0.3mg/kg Sotatercept

0.5mg/kg Sotatercept

0.7mg/kg Sotatercept

Placebo

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

PK-Observed maximum Concentration (Cmax)
PK-Observed maximum Concentration (Cmax)
PK-Time to maximum concentration (Tmax)
PK-Time to maximum concentration (Tmax)
PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d)
PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d)
PK-Terminal half-life (T1/2,z)
PK-Terminal half-life (T1/2,z)

Secondary Outcome Measures

Number of participants with Adverse Events
Number of participants with Adverse Events
Proportion of subjects with Hb > 12g/dL
Proportion of subjects with Hb > 12g/dL
Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period
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
Frequency of clinically significant changes in laboratory parameters from baseline
Blood pressure changes from baseline
Blood pressure changes from baseline
Proportion of subjects that are able to achieve an absolute Hb concentration of > 10 g/dL
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 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
Proportion of subjects rescued and length of time to rescue therapy
Changes in Follicle Stimulating Hormone (FSH) and Sex Steroid Concentrations
Changes in Follicle Stimulating Hormone and Sex Steroid Concentrations

Full Information

First Posted
June 16, 2010
Last Updated
March 7, 2017
Sponsor
Celgene
Collaborators
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
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1. Study Identification

Unique Protocol Identification Number
NCT01146574
Brief Title
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.
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).
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
June 30, 2010 (Actual)
Primary Completion Date
March 7, 2016 (Actual)
Study Completion Date
March 7, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
Collaborators
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
Keywords
End-Stage Renal Disease, Anemia, Hemodialysis, Renal Anemia, ESRD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0.1mg/kg Sotatercept
Arm Type
Experimental
Arm Description
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
Arm Title
0.3mg/kg Sotatercept
Arm Type
Experimental
Arm Description
Dose Group 1: 0.3 mg/kg sotatercept subcutaneous every 28 days
Arm Title
0.5mg/kg Sotatercept
Arm Type
Experimental
Arm Description
Dose Group 2: 0.5 mg/kg sotatercept subcutaneous every 28 days
Arm Title
0.7mg/kg Sotatercept
Arm Type
Experimental
Arm Description
Dose Group 3: 0.7 mg/kg sotatercept subcutaneous every 28 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The Placebo to Sotatercept ratio is 1:3 meaning for every 1 patient that receives Placebo, 3 patients will receive Sotatercept.
Intervention Type
Biological
Intervention Name(s)
Sotatercept
Other Intervention Name(s)
ACE-011
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
PK-Observed maximum Concentration (Cmax)
Description
PK-Observed maximum Concentration (Cmax)
Time Frame
Up to 309 days
Title
PK-Time to maximum concentration (Tmax)
Description
PK-Time to maximum concentration (Tmax)
Time Frame
Up to 309 days
Title
PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d)
Description
PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d)
Time Frame
Up to 309 days
Title
PK-Terminal half-life (T1/2,z)
Description
PK-Terminal half-life (T1/2,z)
Time Frame
Up to 309 days
Secondary Outcome Measure Information:
Title
Number of participants with Adverse Events
Description
Number of participants with Adverse Events
Time Frame
Up to 309 days
Title
Proportion of subjects with Hb > 12g/dL
Description
Proportion of subjects with Hb > 12g/dL
Time Frame
Up to 309 days
Title
Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period
Description
Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period
Time Frame
Up to 309 days
Title
Frequency of clinically significant changes in laboratory parameters from baseline
Description
Frequency of clinically significant changes in laboratory parameters from baseline
Time Frame
Up to 309 days
Title
Blood pressure changes from baseline
Description
Blood pressure changes from baseline
Time Frame
Up to 309 days
Title
Proportion of subjects that are able to achieve an absolute Hb concentration of > 10 g/dL
Description
Proportion of subjects that are able to achieve an absolute Hb concentration of > 10 g/dL
Time Frame
Up to 309 days
Title
Time to reach target Hb concentration (> 10 g/dL) and target increase in Hb (≥ 1g/dL)
Description
Time to reach target Hb concentration (> 10 g/dL) and target increase in Hb (≥ 1g/dL)
Time Frame
Up to 309 days
Title
Proportion of subjects rescued and length of time to rescue therapy
Description
Proportion of subjects rescued and length of time to rescue therapy
Time Frame
Up to 309 days
Title
Changes in Follicle Stimulating Hormone (FSH) and Sex Steroid Concentrations
Description
Changes in Follicle Stimulating Hormone and Sex Steroid Concentrations
Time Frame
Up to 309 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William T Smith, MD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
North American Research Institute
City
Azusa
State/Province
California
ZIP/Postal Code
91702-3439
Country
United States
Facility Name
West Glendale Dialysis
City
Glendale
State/Province
California
ZIP/Postal Code
91205
Country
United States
Facility Name
California Institute of Renal Research
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Academic Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Academic Medical Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Nephrology Specialist Medical Group
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Pines Clinical Research Inc.
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Fresenius Medical Care North America MI
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
DaVita Clinical Research
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Nephrology and Hypertension Associates, LTD
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
St. Louis University Medical Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Kidney Specialists of Southen Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Brookview Hill Research Associates, LLC
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
MetroHealth Medical Systems
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Northeast Clinical Research Center
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Facility Name
Nephrology Associates, PC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37205
Country
United States
Facility Name
Corva Kidney Center Webster
City
Houston
State/Province
Texas
ZIP/Postal Code
77003
Country
United States
Facility Name
Beechnut Dialysis Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77036
Country
United States
Facility Name
Miracle Medical Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77055
Country
United States
Facility Name
Gessner Dialysis Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Tyler Nephrology Associates, PC
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
University of Virginia at University Ave.
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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.

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