Darbepoetin Treatment of Anemia in Children With Chronic Renal Failure

Extended Dosing of Darbepoetin Alfa (Aranesp) for the Management of Anemia in Children With Chronic Renal Failure

This is a study to determine the safety and effectiveness of Darbepoetin (Aranesp) given every 14 to 28 days to treat low red blood cells in children with chronic kidney failure.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Drug: darbepoetin alfa

Detailed Description

Erythropoietin (EPO) is a glycoprotein synthesized in the kidneys which regulates the rate of proliferation and differentiation of red blood cell precursors. The main cause of anemia in children with chronic renal failure is deficiency of EPO production as a result of declining renal function. Recombinant human EPO (rHuEPO) is a synthetic erythropoietin that is structurally and functionally similar to naturally occuring EPO. Treatment of anemia using rHuEPO has been associated with an improvement in the quality of life for patients, likely attributable to an increased production in hemoglobin and a reduction of dilatation of the heart. Recently, an analogue of EPO with two extra oligosaccharide chins, darbepoetin alfa, has been described as having a more prolonged effect requiring less frequent dosing.

There are currently no data available on the efficacy of darbepoetin alfa administered every 14-28 days for children. The most common dosing schedules in the clinical trial at HSC are every 7, 10, and 14 days. Due to reports of increased pain associated with the SC injection, and confusion of caregivers when the 10 day dosing schedule is necessary, the goals of the current proposal are to: 1) Decrease the frequency of SC injections and 2)Eliminate the 10 day dosing schedule for the administration of Darbepoetin.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of chronic renal insufficiency or end stage renal disease (ESRD) requiring dialysis
• clinically stable
• hemoglobin of 110-125 g/L in screening period; for naive subjects, hemoglobin < 110 g/L
• not iron deficient (TSAT > 19.5%) within 4 weeks of study entry
• stable darbepoetin alpha therapy administered IV or SC q7 to q21 days OR darbepoetin alpha naive
• written informed consent from parent/legal guardian
• less than 18 years old
• weight at least 10 kg
• females of childbearing potential must practice adequate contraception
• availability for follow-up assessments

Exclusion Criteria:

• scheduled for a living donor kidney transplant within 12 weeks of signing consent
• uncontrolled blood pressure as judged by principal investigator
• change in seizure pattern in past 30 days; grand-mal seizure 12 weeks before enrollment
• current clinical evidence of severe hyperparathyroidism
• major surgery 2 weeks before signing consent
• active inflammatory disease or condition requiring immunosuppressive therapy
• currently receiving antibiotics for active systemic infection
• peritoneal dialysis patient with an episode of peritonitis within the past 30 days
• known HIV antibody positivity
• known antibodies to rHuEPO
• known aluminum toxicity
• known red cell aplasia
• known malignancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1

Drug: darbepoetin alfa; Darbepoetin alfa will be administered by SC/IV injection every 14-28 days. Patients starting on the 14 day dose regimen will receive two times their baseline weekly dose; patients on the 28 day schedule will receive four times their average weekly dose. The exception to a Q14 or Q28 dosing schedule will be for patients requiring 10 mcg every 10 days. These patients will go to 20 mcg Q21 days before extending to the Q28 day schedule. Naive patients will start on a dose of 0.9 mcg/kg every 14 days. Study subjects who are successfully treated for 12 weeks on the 14 day schedule may be enrolled in the 28 day schedule study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The safety of darbepoetin when administered at an increased dosing interval	40 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of darbepoetin	40 weeks
Proportion of subjects who receive red blood cell transfusions	40 weeks
Percentage of Hb data points that exceed upper target of 125 g/L	16-36 weeks
Incidence of anti-erythropoietin antibody formation	40 weeks

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Denis F Geary, MD, The Hospital for Sick Children, Toronto Canada

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): September 1, 2005
• Study Completion: October 1, 2005

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: pediatrics; anemia; chronic kidney failure; darbepoetin
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: 1000004731

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No