Study to Assess Darbepoetin Alfa Dosing for the Correction of Anemia in Pediatric Patients With Chronic Kidney Disease

This study has been terminated.
(Study Terminated; Commitment met per Regulatory Authorities.)
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00436748
First received: February 15, 2007
Last updated: March 26, 2015
Last verified: March 2015
  Purpose

The primary objectives of this study are the following:

  1. To test if the proportion of participants achieving a hemoglobin value greater than or equal to 10.0 g/dL at any time point after the first dose during the study is greater than 0.8 when administered de novo darbepoetin alfa once a week (QW) for treatment of anemia in pediatric patients with chronic kidney disease receiving and not receiving dialysis, and
  2. To test if the proportion of participants achieving a hemoglobin value greater than or equal to 10.0 g/dL at any time point after the first dose during the study is greater than 0.8 when administered de novo darbepoetin alfa every 2 weeks (Q2W) for treatment of anemia in pediatric patients with chronic kidney disease receiving and not receiving dialysis.

Condition Intervention Phase
Anemia
Chronic Kidney Disease
Kidney Disease
Drug: Darbepoetin Alfa
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-Center, Double-Blind, Randomized Study Evaluating De Novo Weekly and Once Every Two Week Darbepoetin Alfa Dosing for the Correction of Anemia in Pediatric Subjects With Chronic Kidney Disease Receiving and Not Receiving Dialysis

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Proportion of Participants Achieving Hemoglobin ≥ 10.0 g/dL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The proportion of participants achieving hemoglobin ≥ 10.0 g/dL (the correction proportion) was calculated as the number of participants achieving a hemoglobin ≥ 10.0 g/dL at any time point during the study when administered de novo darbepoetin alfa without receiving any red blood cell transfusion after randomization and within 90 days before the achievement, divided by the number of participants in the efficacy analysis set.


Secondary Outcome Measures:
  • Time to First Hemoglobin Value ≥ 10.0 g/dL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The time from study Day 1 to the day a participant first achieved hemoglobin ≥ 10.0 g/dL for participants who achieved hemoglobin ≥ 10.0 g/dL.

  • Hemoglobin Concentration Over Time [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25. ] [ Designated as safety issue: No ]
  • Weight-adjusted Darbepoetin Alfa Dose at Time of Achieving First Hemoglobin ≥ 10.0 g/dL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The darbepoetin alfa dose at the time a participant achieved a first hemoglobin level ≥ 10.0 g/dL, divided by the participant's weight measured at the closest study week prior to the dosing, post dialysis.

  • Darbepoetin Alfa Weight-Adjusted Dose Over Time [ Time Frame: Day 1 (initial dose) and Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25. ] [ Designated as safety issue: No ]
    Arithmetic means are provided; Withheld doses are counted as 0 μg.

  • Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores [ Time Frame: Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25) ] [ Designated as safety issue: No ]
    The PedsQL is a health-related quality of life (HRQOL) questionnaire that can be used to measure quality of life in children ≥ 2 years old. The 23-item PedsQL 4.0 includes physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (5 items). Separate questionnaires for ages 2 to 4 (toddler), 5-7, 8-12, and 13-18 years are used for parent proxy-reporting, which assesses parents' perceptions of their child's HRQOL. The instructions ask how much of a problem each item has been during the past 1 month; each item is answered on a 5-point scale: 0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; 4 = almost always a problem. Scores from the 4 subscales, the total score, and the psychosocial composite score were generated using standard algorithms. Each item's score in the questionnaire was converted to a 0 to 100 scale (with higher scores indicating better HRQOL).

  • Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores [ Time Frame: Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25) ] [ Designated as safety issue: No ]
    The PedsQL child self-reported questionnaire was used in children > 5 years old. The 23-item PedsQL 4.0 includes physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (5 items). Separate questionnaires for ages 5-7, 8-12, and 13-18 years was used for child self-reporting. The instructions asked how much of a problem each item has been during the past 1 month; each item is answered on a 5-point scale for ages 8 to 18 (0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; 4 = almost always a problem), or simplified to a 3-point scale for ages 5 to 7 (0 = not at all a problem; 2 = sometimes a problem; 4 = a lot of a problem). Scores from the 4 subscales, the total score, and the psychosocial composite score were generated using standard algorithms. Each item's score in the questionnaire was converted to a 0 to 100 scale (with higher scores indicating better HRQOL).

  • Number of Participants With Treatment-emergent Adverse Events [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]
    A serious adverse event (SAE) is defined as an adverse event that meets at least one of the following serious criteria: • is fatal, • is life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • is a congenital anomaly/birth defect, and/or • other significant medical hazard. The investigator assessed whether the adverse event was related to the investigational product (IP). Events of interest included hypertension, ischemic heart disease, cardiac failure, cerebrovascular disorders, convulsions, embolic and thrombotic events, embolic and thrombotic events: venous, embolic and thrombotic events: arterial, embolic and thrombotic events: vessel type unspecified and mixed arterial and venous, dialysis vascular access thrombosis, antibody-mediated pure red cell aplasia, hypersensitivity, lack of efficacy-effect, and malignancies.

  • Hemoglobin Serial Rate of Change (ROC) Over Time [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25. ] [ Designated as safety issue: No ]
    Calculated using the serial method as the change in hemoglobin from the previous non-missing hemoglobin level divided by number of days in between, and then multiplied by 7.

  • Number of Participants With Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]
  • Maximum Increase in Hemoglobin Over Any 2 Week Period [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]
    The maximum increase between any 2 non-missing hemoglobin measurements over any 2-week period from Day 1.

  • Change From Baseline in Systolic Blood Pressure Over Time [ Time Frame: Baseline and Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25. ] [ Designated as safety issue: No ]
  • Change From Baseline in Diastolic Blood Pressure Over Time [ Time Frame: Baseline and Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25. ] [ Designated as safety issue: No ]
  • Number of Participants Who Developed Anti-erythropoiesis Antibodies [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]
    Participants who were negative for anti-erythropoiesis antibodies at Baseline (pre-dose) and who developed anti-erythropoiesis antibodies during the study. Serum samples were tested using Amgen's Surface Plasmon Resonance Immunoassay (SPRIA) method.

  • Darbepoetin Alfa Serum Concentrations for Participants Less Than 6 Years of Age [ Time Frame: Weeks 1, 2, and 3 before the investigational product dose and 2 days after the first investigational product dose ] [ Designated as safety issue: No ]
    Serum concentrations of darbepoetin alfa were measured by an enzyme-linked immunosorbent assay (ELISA).


Enrollment: 116
Study Start Date: September 2008
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Darbepoetin Alfa QW
Participants received darbepoetin alfa once a week (QW) for 24 weeks. The initial dose was 0.45 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.
Drug: Darbepoetin Alfa
Administered by subcutaneous or intravenous injection
Other Name: Aranesp®
Experimental: Darbepoetin Alfa Q2W
Participants received darbepoetin alfa every 2 weeks (Q2W) and a placebo every other 2 weeks to maintain the blind for 24 weeks. The initial dose was 0.75 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.
Drug: Darbepoetin Alfa
Administered by subcutaneous or intravenous injection
Other Name: Aranesp®
Drug: Placebo
Matching placebo solution for subcutaneous or intravenous injection to maintain the blind in the Q2W arm.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Current diagnosis of Chronic Kidney Disease, either receiving or not receiving dialysis
  • Anemic, with two consecutive screening hemoglobin values drawn at least 7 days apart < 11.0 g/dL
  • Transferrin saturation (Tsat) greater than or equal to 20%

Exclusion Criteria:

  • Any erythropoiesis stimulating agent (ESA) use within 12 weeks prior to randomization
  • other hematologic disorders
  • upper or lower gastrointenstinal bleeding within 6 months prior to randomization
  • uncontrolled hypertension
  • prior history (within 12 weeks prior to randomization) of acute myocardial ischemia, hospitalization for congestive heart failure, myocardial infarction, stroke or transient ischemic attack
  • prior history (within 6 months prior to randomization) of thromboembolism
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436748

  Show 67 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00436748     History of Changes
Other Study ID Numbers: 20050256
Study First Received: February 15, 2007
Results First Received: March 4, 2015
Last Updated: March 26, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Chronic Kidney Disease
Dialysis
Anemia
Nephrology
Pediatric
Hemodialysis
Peritoneal Dialysis
Chronic Renal Insufficiency

Additional relevant MeSH terms:
Anemia
Kidney Diseases
Renal Insufficiency, Chronic
Hematologic Diseases
Renal Insufficiency
Urologic Diseases
Darbepoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015