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

Anemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00436748
• Other study ID #: 20050256
• Status: Terminated
• Phase: Phase 3
• Start date: September 16, 2008
• Est. completion date: March 3, 2014

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 116
• Est. completion date: March 3, 2014
• Est. primary completion date: March 3, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Darbepoetin Alfa
Administered by subcutaneous or intravenous injection
• Placebo
Matching placebo solution for subcutaneous or intravenous injection to maintain the blind in the Q2W arm.

Locations

Country	Name	City	State
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Latvia	Research Site	Jurmala
Lithuania	Research Site	Vilnius
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Chihuahua
Mexico	Research Site	Mexico	Distrito Federal
Mexico	Research Site	Puebla
Poland	Research Site	Gdansk
Poland	Research Site	Lodz
Poland	Research Site	Szczecin
Puerto Rico	Research Site	San Juan
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Orenburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Samara
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United States	Research Site	Akron	Ohio
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Baltimore	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Gainesville	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Iowa City	Iowa
United States	Research Site	Kansas City	Missouri
United States	Research Site	Livingston	New Jersey
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Miami	Florida
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New Hyde Park	New York
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	Norfolk	Virginia
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Richmond	Virginia
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Francisco	California
United States	Research Site	Seattle	Washington
United States	Research Site	Stanford	California
United States	Research Site	Valhalla	New York
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  Latvia,  Lithuania,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Slovakia,  United Kingdom, 

References & Publications (1)

Warady BA, Barcia J, Benador N, Jankauskiene A, Olson K, Podracka L, Shavkin A, Srivaths P, Wong CJ, Petersen J. De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease. Pediatr Nephrol. 2018 Jan;33(1):125-137. doi: 10.1007/s00467-017-3758-5. Epub 2017 Aug 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Achieving Hemoglobin = 10.0 g/dL	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.	24 weeks
Secondary	Time to First Hemoglobin Value = 10.0 g/dL	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.	24 weeks
Secondary	Hemoglobin Concentration Over Time		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.
Secondary	Weight-adjusted Darbepoetin Alfa Dose at Time of Achieving First Hemoglobin = 10.0 g/dL	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.	24 weeks
Secondary	Darbepoetin Alfa Weight-Adjusted Dose Over Time	Arithmetic means are provided; Withheld doses are counted as 0 µg.	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.
Secondary	Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores	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).	Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25)
Secondary	Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores	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).	Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25)
Secondary	Number of Participants With Treatment-emergent Adverse Events	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.	25 weeks
Secondary	Hemoglobin Serial Rate of Change (ROC) Over Time	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.	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.
Secondary	Number of Participants With Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study		25 weeks
Secondary	Maximum Increase in Hemoglobin Over Any 2 Week Period	The maximum increase between any 2 non-missing hemoglobin measurements over any 2-week period from Day 1.	25 weeks
Secondary	Change From Baseline in Systolic Blood Pressure Over Time		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.
Secondary	Change From Baseline in Diastolic Blood Pressure Over Time		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.
Secondary	Number of Participants Who Developed Anti-erythropoiesis Antibodies	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.	25 weeks
Secondary	Darbepoetin Alfa Serum Concentrations for Participants Less Than 6 Years of Age	Serum concentrations of darbepoetin alfa were measured by an enzyme-linked immunosorbent assay (ELISA).	Weeks 1, 2, and 3 before the investigational product dose and 2 days after the first investigational product dose

External Links

•   AmgenTrials clinical trials website