Peginesatide for Anemia in Chronic Hemodialysis Patients

A Phase 2, Open-label, Multi-center, Sequential, Dose Finding Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Peginesatide Administered Intravenously for the Maintenance Treatment of Anemia in Chronic Hemodialysis Patients

The purpose of this study is to evaluate the safety, pharmacodynamics (PD), and pharmacokinetics (PK) of multiple intravenous doses of peginesatide in participants with chronic kidney disease (CKD) who are on hemodialysis.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; Chronic Renal Failure
• Intervention / Treatment: Drug: peginesatide

Detailed Description

This was a Phase 2, multicenter, open-label, sequential, dose-finding trial designed with up to 12 treatment cohorts of 15 participants per cohort. Each participant received an intravenous dose of peginesatide administered once every 4 weeks (Q4W) for a total of 6 doses. Dosage regimens varied by cohort. Participants were followed for a minimum of 42 days after the last administration of peginesatide.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Research Facility
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • Research Facility
  • California
    • Los Angeles, California, United States, 90095
      • Research Facility
    • Mountain View, California, United States, 94041
      • Research Facility
  • Florida
    • Lauderdale Lakes, Florida, United States, 33313
      • Research Facility
    • Pembroke Pines, Florida, United States, 33028
      • Research Facility
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Research Facility
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Facility
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Research Facility
  • New York
    • New York, New York, United States, 10128
      • Research Facility
  • Ohio
    • Canton, Ohio, United States, 44718
      • Research Facility
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Research Facility
  • Texas
    • San Antonio, Texas, United States, 78215
      • Research Facility
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines;
• Males or females ≥ 18 years of age. Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study start, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence (only acceptable if practiced as a life-style and not acceptable if one who is sexually active practices abstinence only for the duration of the study) or vasectomized partner;
• Clinically stable on hemodialysis for ≥6 months prior to study drug administration;
• Urea clearance/volume (Kt/V) ≥ 1.2 within the 4 weeks prior to study drug administration;
• Epoetin alfa maintenance therapy of ≥ 60 and ≤ 375 U/kg/wk continuously prescribed for 8 weeks prior to study drug administration. In the last 3 weeks prior to study drug administration, variation in prescribed total weekly dose must be ≤ 25% from the mean of the last three prescribed total weekly doses;
• Three mid- or end-of-week hemoglobin values of ≥ 10.0 and ≤ 12.5 g/dL in the 3 weeks prior to study drug administration with ≤ 1.2 g/dL difference between the three values;
• One serum ferritin level ≥ 100 micrograms per liter (μg/L) or one transferrin saturation ≥ 20% or one reticulocyte hemoglobin content (CHr) ≥ 29 picograms within 4 weeks prior to study drug administration;
• One serum folate level above the lower limit of normal during the 4 weeks prior to study drug administration;
• One vitamin B12 level above the lower limit of normal during the 4 weeks prior to study drug administration;
• Weight ≥ 45 kilograms (kg) within the 4 weeks prior to study drug administration;
• One white blood cell count ≥ 3.0 x 10^9/L within 4 weeks prior to study drug administration; and
• One platelet count ≥ 100 x 10^9/L and ≤ 500 x 10^9/L within 4 weeks prior to study drug administration.

Exclusion Criteria:

• Known intolerance to erythropoiesis stimulating agents;
• History of antibodies to erythropoiesis stimulating agents or history of pure red cell aplasia;
• Known intolerance to parenteral iron supplementation;
• Red blood cell transfusion within 12 weeks prior to study drug administration;
• Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.);
• Known hemolysis;
• Chronic, uncontrolled, or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.);
• C-reactive protein greater than 30 mg/L within the 4 weeks prior to study drug administration;
• Moderate or significant infection within 2 weeks prior to study drug administration;
• Known coagulation disorder based on clinical context and laboratory [activated partial thromboplastin time (aPTT) or international normalized ratio (INR)] results;
• Temporary (untunneled) dialysis access catheter;
• Uncontrolled or symptomatic secondary hyperparathyroidism;
• Poorly controlled hypertension within the 4 weeks prior to study drug administration, per the Investigator's clinical judgment (e.g., systolic ≥ 170 mm Hg or diastolic ≥ 100 mm Hg on repeat readings);
• Any history of multiple significant drug allergies;
• History of severe or unstable reactive airway disease within the previous 10 years;
• Epileptic seizure in the 6 months prior to screening;
• Chronic congestive heart failure (New York Heart Association Class IV);
• High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, respiratory, autoimmune, neuropsychiatric, or neurological abnormalities, liver disease including active hepatitis B or C, active HIV disease, or any other clinically significant medical disease or conditions in the prior 6 months that may, in the Investigator's opinion, interfere with assessment or follow-up of the patient);
• Evidence of malignancy within the past 5 years (except non-melanoma skin cancer which is not an exclusion criterion);
• Life expectancy < 12 months;
• Anticipated elective surgery during the study period; and
• Previous exposure to any investigational agent within 6 weeks prior to administration of study drug or planned receipt during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Conversion from epoetin alfa to peginesatide with a conversion factor (CF) of 0.033: peginesatide dose administered intravenously once every 4 weeks (Q4W) for a total of up to 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohort 2; Conversion from epoetin alfa to peginesatide with a CF of 0.041: peginesatide dose administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohort 3; Conversion from epoetin alfa to peginesatide with a CF of 0.050: peginesatide dose administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohorts 4 and 9; Conversion from epoetin alfa to peginesatide with a CF of 0.050: peginesatide dose administered intravenously Q4W for a total of 6 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohort 5; Conversion from epoetin alfa to peginesatide with a CF of 0.066: peginesatide dose administered intravenously Q4W for a total of 6 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohort 6; Conversion from epoetin alfa to peginesatide with tiered peginesatide starting doses of 0.05, 0.075, 0.1 or 0.15 mg/kg based on total weekly doses of epoetin alfa . Doses were administered intravenously Q4W for a total of 6 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohorts 7 and 8; Conversion from epoetin alfa to peginesatide with tiered peginesatide starting doses of 0.05, 0.075, 0.1 or 0.15 mg/kg based on total weekly doses of epoetin alfa dose. Doses were administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection
Experimental: Cohorts 10 and 11; Conversion from epoetin alfa to peginesatide with fixed peginesatide starting doses of 4, 6, 12 or 16 mg based on total weekly doses of epoetin alfa. Doses were administered intravenously Q4W for a total of 6 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Drug: peginesatide; Other Names: Omontys; Hematide; AF37702 Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Average weekly hemoglobin and hemoglobin change from baseline	Baseline to Week 27

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with hemoglobin within 1.0 gram per deciliter (g/dL) above or below baseline	Baseline to Week 25
Percentage of participants who maintain hemoglobin within 9.5-13.0 g/dL	Baseline to Week 25
Percentage of participants who maintain hemoglobin within 11.0-13.0 g/dL	Baseline to Week 25

Collaborators and Investigators

• Sponsor: Affymax
• Investigators: Study Director: Affymax, Affymax, Inc.

Publications and helpful links

General Publications

• Besarab A, Zeig SN, Martin ER, Pergola PE, Whittier FC, Zabaneh RI, Schiller B, Mayo M, Francisco CA, Polu KR, Duliege AM. An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients. BMC Nephrol. 2012 Aug 30;13:95. doi: 10.1186/1471-2369-13-95.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: September 27, 2005
• First Submitted That Met QC Criteria: September 27, 2005
• First Posted (Estimate): September 29, 2005

Study Record Updates

• Last Update Posted (Estimate): December 21, 2012
• Last Update Submitted That Met QC Criteria: December 19, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: hemoglobin; anemia; chronic kidney disease; erythropoiesis stimulating agent; dialysis; CKD; CRF; Hgb; erythropoietin; hemodialysis; chronic renal failure; EPO; ESA; Hematide™; Hb; Omontys; peginesatide; red blood cell; red blood cell production
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Anemia
• Other Study ID Numbers: AFX01-03