A Study to Evaluate Ferumoxytol for the Treatment of Iron Deficiency Anemia (IDA) in Pediatric Subjects

Subjects will be randomized to treatment in a 2:1 ratio (ferumoxytol: iron sucrose) and stratified by age group (2 to <6 years; 6 to <12 years; and 12 to <18 years). Subjects will receive one of the following treatment regimens:

• Ferumoxytol: 7 mg Fe/kg IV (maximum 510 mg/dose) x 2 doses, the first dose administered on Day 1 and the second 2 to 8 days later.

OR

• Iron sucrose (Venofer®): 4 mg Fe/kg IV (maximum 200 mg/dose) x 5 doses, the first dose on Day 1 and subsequent doses administered at least once per week and up to 3 times/week. All subjects will be monitored at the study site through at least 1 hour after the completion of each infusion of study drug. Assessment of blood Hgb concentrations, adverse events, and other safety assessments will be performed through study Week 5.

• ferumoxytol (Drug), also known as Feraheme: 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
• Iron sucrose (Drug), also known as Venofer: 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).

Primary outcomes

• Change in Hemoglobin from Baseline to Week 5 [35 days]: Proportion of subjects achieving a change in hemoglobin from Baseline to Week 5

Secondary outcomes

• Incidence of Treatment Emergent Adverse Events [49 days]: Incidence of Treatment Emergent Adverse Events
• Incidence of adverse events of special interest (AESI) [49 days]: Incidence of adverse events of special interest (AESI) (hypotension and hypersensitivity)

Other outcomes

• Area Under the Curve (AUC) [35 days]: Pharmacokinetic parameter: Area Under the Curve (AUC)
• Clearance [35 days]: Pharmacokinetic parameter: Clearance
• Distribution [35 days]: Pharmacokinetic parameter: Distribution
• Elimination half-lives [35 days]: Pharmacokinetic parameter: Elimination half-lives

Sex: All, ages: 2 Years to 17 Years

Inclusion Criteria:

1. Male or female 2 years to <18 years of age at time of consent
2. Has IDA defined as:

   1. Hemoglobin (Hgb) <11.0 g/dL AND
   2. Any one or more of the following:

      * Transferrin saturation (TSAT) <20%
      * ferritin <100 ng/mL
3. Documented history of unsatisfactory oral iron therapy or in whom oral iron cannot be tolerated, or for whom oral iron is considered medically inappropriate

Exclusion Criteria:

1. Known hypersensitivity reaction to any component of ferumoxytol or iron sucrose
2. History of allergy to intravenous (IV) iron
3. History of ≥2 clinically significant drug allergies
4. Subjects with CKD (defined as eGFR of <60 mL/min/1.73 m2 or a requirement for chronic hemodialysis or peritoneal dialysis during Screening)
5. Low systolic blood pressure (BP) (age 1 to 9 years <70 + \[age in years x 2\] mmHg, age 10 to 17 years <90 mmHg)
6. Hgb ≤7.0 g/dL
7. Serum ferritin level >600 ng/mL