A Study to Evaluate the Safety (Compared to Iron Sucrose), Efficacy and Pharmacokinetics of Ferumoxytol for the Treatment of Iron Deficiency Anemia (IDA) in Pediatric Subjects With Chronic Kidney Disease (CKD)

Study Overview
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Brief Summary
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Primary Objectives: To evaluate the safety (compared to iron sucrose) and efficacy of ferumoxytol in pediatric CKD subjects with iron deficiency anemia (IDA) or who are at risk of development of IDA Secondary Objective: To determine the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) profile of ferumoxytol in pediatric subjects.

Detailed Description
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This is a Phase 3, randomized, open-label, multicenter, study of the safety (compared to iron sucrose), efficacy, and PK/PD of ferumoxytol (7.0 mg Fe/kg x 2 [max 510 mg/dose]) in pediatric subjects with iron deficiency anemia (IDA) and CKD. There will be a total of approximately 125 subjects randomized to treatment in a 2:1 ratio to either ferumoxytol or iron sucrose. Total subject participation in the study will be up to 7 weeks, which includes a 2-week Screening Period and a 5-week Treatment Period. Subjects receive the following: • Two IV infusions of ferumoxytol 7.0 mg Fe/kg (max 510 mg/dose), the first administered on Day 1 and the second 2-8 days later OR • Iron sucrose (Venofer®): For Hemodialysis Dependent (HDD) patients: 2 mg Fe/kg, administered on consecutive dialysis sessions, for 10 doses (max 100mg/dose with a total max treatment course of 1000mg) For Non-hemodialysis Dependent (NDD) or Peritoneal Dialysis De pendent(PDD) patients: 4 mg Fe/kg, administered up to 3 times/week, for 5 doses (max 200mg/dose with a total max treatment course of 1000mg).

Official Title
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A Phase 3, Randomized, Open-Label, Multicenter Study to Evaluate the Safety (Compared to Iron Sucrose), Efficacy and Pharmacokinetics of Ferumoxytol for the Treatment of Iron Deficiency Anemia (IDA) in Pediatric Subjects With Chronic Kidney Disease (CKD)

Conditions
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Chronic Kidney Disease; Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Ferumoxytol
* Drug: Iron sucrose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 2 years to <18 years of age at time of consent Has IDA defined as: a) hemoglobin <12.0 g/dL and b) with either transferrin saturation (TSAT) <40% or ferritin <100 ng/mL; or considered to be at risk of development of IDA, i.e., TSAT<20% with falling hemoglobin during the preceding 2 months and a history of hemoglobin <12 g/dL Has Chronic Kidney Disease defined as one of the following: on chronic hemodialysis; receiving chronic peritoneal dialysis; estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2; has evidence of structural and/or functional abnormalities e.g., persistent albuminuria, abnormal urine sediment, electrolyte and other abnormalities due to tubular disorders for > 3 months. For patients other than hemodialysis dependent CKD patients, documented history of unsatisfactory oral iron therapy or in whom oral iron cannot be tolerated, or for whom oral iron is considered medically inappropriate All subjects (female and male) of childbearing potential who are sexually active must be on an effective method of birth control for at least 1 month prior to Day 1 Dosing and agree to remain on birth control until completion of the study Exclusion Criteria: Known hypersensitivity reaction to any component of ferumoxytol and iron sucrose History of allergy to intravenous (IV) iron History of multiple drug allergies (>2) Low systolic blood pressure (Age 1-9 years <70 + [age in years x 2] mmHg, Age 10-17 years <90 mmHg) Hemoglobin ≤7.0 g/dL Serum ferritin level >600 ng/mL

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferumoxytol<br> | Drug: Ferumoxytol<br>* Each 20 mL single-use vial contains 17 mL of ferumoxytol that consists of iron at a concentration of 30 mg Fe/mL, coated with polyglucose sorbitol carboxymethylether and formulated with mannitol, at a concentration of 44 mg/mL, in a black to reddish brown sterile, aqueous, colloidal, isotonic solution.<br>* Other names: Feraheme;|
| Active Comparator: Iron sucrose<br> | Drug: Iron sucrose<br>* Each mL contains 20 mg of elemental iron as iron sucrose in water for injection. The 5 mL single-use vial contains 100 mg of iron per 5 mL. The drug product contains approximately 30% sucrose (300 mg/mL).<br>* Other names: Venofer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin change of at least 0.5 g/dL from Baseline to Week 5 | Proportion of patients achieving a hemoglobin change of at least 0.5 g/dL during the period from Baseline to Week 5 | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events | Incidence of Treatment Emergent Adverse Events | 49 days | 
| Incidence of adverse events of special interest (AESI) | Incidence of adverse events of special interest (AESI) (hypotension and hypersensitivity) | 49 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron deficiency anemia (IDA), chronic kidney disease (CKD), pediatrics, ferumoxytol, iron sucrose, Feraheme, Venofer