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).

Sponsors

Lead Sponsor: Celgene

Collaborator: Acceleron Pharma, Inc.

Source Celgene
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.

Overall Status Completed
Start Date June 30, 2010
Completion Date March 7, 2016
Primary Completion Date March 7, 2016
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
PK-Observed maximum Concentration (Cmax) Up to 309 days
PK-Time to maximum concentration (Tmax) Up to 309 days
PK-Area under the concentration-time curve over the 28 day dosing interval (AUC 28d) Up to 309 days
PK-Terminal half-life (T1/2,z) Up to 309 days
Secondary Outcome
Measure Time Frame
Number of participants with Adverse Events Up to 309 days
Proportion of subjects with Hb > 12g/dL Up to 309 days
Proportion of subjects with rise in Hb > 2 g/dL during a 4 week period Up to 309 days
Frequency of clinically significant changes in laboratory parameters from baseline Up to 309 days
Blood pressure changes from baseline Up to 309 days
Proportion of subjects that are able to achieve an absolute Hb concentration of > 10 g/dL Up to 309 days
Time to reach target Hb concentration (> 10 g/dL) and target increase in Hb (≥ 1g/dL) Up to 309 days
Proportion of subjects rescued and length of time to rescue therapy Up to 309 days
Changes in Follicle Stimulating Hormone (FSH) and Sex Steroid Concentrations Up to 309 days
Enrollment 50
Condition
Intervention

Intervention Type: Biological

Intervention Name: Sotatercept

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

Other Name: ACE-011

Intervention Type: Biological

Intervention Name: Placebo

Description: Placebo

Arm Group Label: Placebo

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
William T Smith, MD Study Director Celgene Corporation
Location
Facility:
North American Research Institute | Azusa, California, 91702-3439, United States
West Glendale Dialysis | Glendale, California, 91205, United States
California Institute of Renal Research | La Mesa, California, 91942, United States
Academic Medical Center | Los Angeles, California, 90022, United States
Academic Medical Research Institute | Los Angeles, California, 90022, United States
Nephrology Specialist Medical Group | Orange, California, 92868, United States
Pines Clinical Research Inc. | Pembroke Pines, Florida, 33028, United States
University of Kentucky | Lexington, Kentucky, 40536, United States
Fresenius Medical Care North America MI | Kalamazoo, Michigan, 49007, United States
DaVita Clinical Research | Minneapolis, Minnesota, 55404, United States
Nephrology and Hypertension Associates, LTD | Tupelo, Mississippi, 38801, United States
St. Louis University Medical Center | St. Louis, Missouri, 63110, United States
Washington University School of Medicine | St. Louis, Missouri, 63110, United States
Kidney Specialists of Southen Nevada | Las Vegas, Nevada, 89106, United States
Brookview Hill Research Associates, LLC | Winston-Salem, North Carolina, 27103, United States
MetroHealth Medical Systems | Cleveland, Ohio, 44109, United States
Northeast Clinical Research Center | Bethlehem, Pennsylvania, 18017, United States
Nephrology Associates, PC | Nashville, Tennessee, 37205, United States
Corva Kidney Center Webster | Houston, Texas, 77003, United States
Beechnut Dialysis Center | Houston, Texas, 77036, United States
Miracle Medical Clinic | Houston, Texas, 77055, United States
Gessner Dialysis Center | Houston, Texas, 77074, United States
Tyler Nephrology Associates, PC | Tyler, Texas, 75702, United States
University of Virginia at University Ave. | Charlottesville, Virginia, 22908, United States
Location Countries

United States

Verification Date

March 2017

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 5
Arm Group

Label: 0.1mg/kg Sotatercept

Type: Experimental

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

Label: 0.3mg/kg Sotatercept

Type: Experimental

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

Label: 0.5mg/kg Sotatercept

Type: Experimental

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

Label: 0.7mg/kg Sotatercept

Type: Experimental

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

Label: Placebo

Type: Placebo Comparator

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

Study Design Info

Allocation: Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: Single (Participant)

Source: ClinicalTrials.gov