Clinical trial NCT01146574: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Keywords: End-Stage Renal Disease
Anemia
Hemodialysis
Renal Anemia
ESRD
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
First posted: 2010-06-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Observed Maximum Concentration (Cmax)
timeFrame: From first dose up to Day 28
measure: Time to Maximum Concentration (Tmax)
timeFrame: From first dose up to Day 28
measure: Area Under Curve (AUC)-28 Days
timeFrame: From first dose up to Day 28
measure: AUCinf: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity
timeFrame: From first dose up to Day 28
measure: Apparent Total Clearance (CL/F)
timeFrame: From first dose up to Day 28
measure: Apparent Volume of Distribution Based on Terminal Phase (Vz/F)
timeFrame: From first dose up to Day 28
measure: Terminal Half-Life (t1/2,z)
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 85 and 113
Secondary outcomes:
measure: The Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 115 days post last dose
measure: Number of Participants With Hemoglobin > 12g/dL
timeFrame: Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
measure: Proportion of Participants With Rise in Hemoglobin > 2 g/dL During 4 Week Period
timeFrame: Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
measure: Blood Pressure Changes From Baseline
timeFrame: From pre-dose up to the final visit 112 days after last dose (up to 225 days)
measure: Changes in Follicle Stimulating Hormone (FSH)
timeFrame: Day 1 (baseline), Day 15, Day 29, and Day 113
measure: Number of Participants With Hemoglobin > 10g/dL
timeFrame: Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
measure: Number of Participants With Change From Baseline Hemoglobin ≥ 1g/dL
timeFrame: Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
measure: Number of Participants With Hemoglobin > 10g/dL and Change From Baseline Hemoglobin ≥ 1g/dL
timeFrame: Pre-dose; Dose 1-Days 1, 8, 15, 22, 29; Doses 2, 3, 4, 5, 6, 7-Days 1, 15, 29; Follow-up Phase Days 225, 253, 281, and 309
measure: Length of Time to Rescue Therapy
timeFrame: From first dose up to blood transfusion or ESA therapy, up to approximately 209 days
measure: Change From Baseline in Hemoglobin Values
timeFrame: From first dose up to Day 225
Other outcomes:
Locations:
city: Azusa
country: United States
facility: North American Research Institute
state: California
city: Glendale
country: United States
facility: West Glendale Dialysis
state: California
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Los Angeles
country: United States
facility: Academic Medical Center
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Orange
country: United States
facility: Nephrology Specialist Medical Group
state: California
city: Pembroke Pines
country: United States
facility: Pines Clinical Research Inc.
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Kalamazoo
country: United States
facility: Fresenius Medical Care North America MI
state: Michigan
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
city: Tupelo
country: United States
facility: Nephrology and Hypertension Associates, LTD
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis University Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Kidney Specialists of Southen Nevada
state: Nevada
city: Winston-Salem
country: United States
facility: Brookview Hill Research Associates, LLC
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Systems
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: Nashville
country: United States
facility: Nephrology Associates, PC
state: Tennessee
city: Houston
country: United States
facility: Corva Kidney Center Webster
state: Texas
city: Houston
country: United States
facility: Beechnut Dialysis Center
state: Texas
city: Houston
country: United States
facility: Miracle Medical Clinic
state: Texas
city: Houston
country: United States
facility: Gessner Dialysis Center
state: Texas
city: Tyler
country: United States
facility: Tyler Nephrology Associates, PC
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia at University Ave.
state: Virginia
Study officials:
affiliation: Celgene Corporation
name: William T Smith, MD
role: STUDY_DIRECTOR
References: