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.

Anemia Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01146574
• Other study ID #: ACE-011-REN-001
• Status: Completed
• Phase: Phase 2
• Start date: June 30, 2010
• Est. completion date: March 7, 2016

Study information

• Verified date: February 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is the first study in hemodialysis subjects with anemia to evaluate the pharmacokinetics, safety, efficacy, tolerability, and pharmacodynamics of sotatercept (ACE-011)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 7, 2016
• Est. primary completion date: March 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

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
• Placebo
Placebo

Locations

Country	Name	City	State
United States	North American Research Institute	Azusa	California
United States	Northeast Clinical Research Center	Bethlehem	Pennsylvania
United States	University of Virginia at University Ave.	Charlottesville	Virginia
United States	MetroHealth Medical Systems	Cleveland	Ohio
United States	West Glendale Dialysis	Glendale	California
United States	Beechnut Dialysis Center	Houston	Texas
United States	Corva Kidney Center Webster	Houston	Texas
United States	Gessner Dialysis Center	Houston	Texas
United States	Miracle Medical Clinic	Houston	Texas
United States	Fresenius Medical Care North America MI	Kalamazoo	Michigan
United States	California Institute of Renal Research	La Mesa	California
United States	Kidney Specialists of Southen Nevada	Las Vegas	Nevada
United States	University of Kentucky	Lexington	Kentucky
United States	Academic Medical Center	Los Angeles	California
United States	Academic Medical Research Institute	Los Angeles	California
United States	DaVita Clinical Research	Minneapolis	Minnesota
United States	Nephrology Associates, PC	Nashville	Tennessee
United States	Nephrology Specialist Medical Group	Orange	California
United States	Pines Clinical Research Inc.	Pembroke Pines	Florida
United States	St. Louis University Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Nephrology and Hypertension Associates, LTD	Tupelo	Mississippi
United States	Tyler Nephrology Associates, PC	Tyler	Texas
United States	Brookview Hill Research Associates, LLC	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Celgene	Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed Maximum Concentration (Cmax)	Cmax is a pharmacokinetic parameter defined as the observed maximum concentration of the study drug in the serum and/or blood. Cmax will be estimated from the sotatercept concentration versus time data using noncompartmental method.	From first dose up to Day 28
Primary	Time to Maximum Concentration (Tmax)	Time to observed maximum concentration (Tmax) is defined as the amount of time in days for a drug to reach the maximum concentration after administration.	From first dose up to Day 28
Primary	Area Under Curve (AUC)-28 Days	AUC-28 days is defined as area under the concentration-time curve over the first 28-day dosing interval	From first dose up to Day 28
Primary	AUCinf: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity	Area under the concentration-time curve from time zero extrapolated to infinity. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.	From first dose up to Day 28
Primary	Apparent Total Clearance (CL/F)	Apparent Total Clearance (CL/F) is defined as the volume of plasma from which the study drug is completely removed per unit of time. It is equal to the drug dose divided by the area-under-the-curve.	From first dose up to Day 28
Primary	Apparent Volume of Distribution Based on Terminal Phase (Vz/F)	Apparent volume of distribution based on terminal phase (Vz/F) is defined as the apparent volume in which the current amount of drug in the body must be dispersed in order to give the current plasma concentration. Apparent volume of distribution is important for determining the dose required to produce a desired plasma concentration of the drug.	From first dose up to Day 28
Primary	Terminal Half-Life (t1/2,z)	Terminal plasma half-life (t1/2,z) is the time taken for concentration of the study drug to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma.	Days 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 85 and 113
Secondary	The Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose up to 115 days post last dose
Secondary	Number of Participants With Hemoglobin > 12g/dL	Number of participants with hemoglobin > 12g/dL including Hb values obtained after first study drug dose and before any rescue.	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
Secondary	Proportion of Participants With Rise in Hemoglobin > 2 g/dL During 4 Week Period	Proportion of participants with rise in hemoglobin (Hb) > 2 g/dL during a 4-week period including Hb values obtained after first study drug dose and before any rescue.	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
Secondary	Blood Pressure Changes From Baseline	Blood pressure was generally recorded on the day of dialysis and represent pre-dialysis values. Baseline is defined as blood pressure measurements recorded on Day 1 of the first dose administered.	From pre-dose up to the final visit 112 days after last dose (up to 225 days)
Secondary	Changes in Follicle Stimulating Hormone (FSH)	The change in follicle stimulating measured at pre-specified timepoints throughout the treatment period.	Day 1 (baseline), Day 15, Day 29, and Day 113
Secondary	Number of Participants With Hemoglobin > 10g/dL	Number of participants with hemoglobin > 10g/dL including Hb values obtained after first study drug dose and before any rescue. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	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
Secondary	Number of Participants With Change From Baseline Hemoglobin = 1g/dL	Number of participants with a change from in hemoglobin values = 1g/dL including Hb values obtained after first study drug dose and before any rescue. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	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
Secondary	Number of Participants With Hemoglobin > 10g/dL and Change From Baseline Hemoglobin = 1g/dL	Number of participants with Hemoglobin > 10g/dL and a change from in hemoglobin values = 1g/dL including Hb values obtained after first study drug dose and before any rescue. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	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
Secondary	Length of Time to Rescue Therapy	The length of time in days that participants who were rescued received treatment. When applicable, participants were rescued for anemia. During the rescue, participants discontinued sotatercept and were unblinded to the study treatment. Participants who were rescued continued in the treatment phase of 200 days and a follow-up phase of 112 days after the treatment phase. Rescue is defined as the need for a blood transfusion or Erythropoiesis-stimulating agent (ESA) therapy.	From first dose up to blood transfusion or ESA therapy, up to approximately 209 days
Secondary	Change From Baseline in Hemoglobin Values	Dose Cycle 1 is defined as the first 28 days of treatment for Dose Groups 0.3 mg/kg, 0.5 mg/kg, and 0.7 mg/kg and the first 14 days of treatment for Dose Group 0.7/0.4 mg/kg. End of the Treatment Period is defined as the day before the follow-up phase started. Baseline is defined as hemoglobin measurements recorded on Day 1 of the first dose administered.	From first dose up to Day 225