A Randomized, Open-Label, Active-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of Ferumoxytol Compared with Oral Iron for the Treatment of Iron Deficiency Anemia in Pediatric Subjects with Nondialysis-dependent Chronic Kidney Disease

INTERVENTION: Trade Name: Feraheme (TM) Product Name: ferumoxytol Pharmaceutical Form: Solution for injection CAS Number: 722492‐56‐0 Current Sponsor code: 7228; ferumoxytol drug substance Other descriptive name: polyglucose sorbitol carboxymethylether (PCS) superparamagnetic iron oxide Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 30‐ Product Name: ferrous sulfate Product Code: ‐ Pharmaceutical Form: Oral liquid Other descriptive name: ferrous sulfate Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ CONDITION: Nondialysis dependent Chronic Kidney Disease ; MedDRA version: 13.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 ‐ Renal and urinary disorders INCLUSION CRITERIA: 1. Male or female 6 months to <18 years of age 2. Nondialysis dependent CKD, including kidney transplant recipients 3. Has IDA defined as: a) hemoglobin <11.0 g/dL and b) TSAT <20% 4. Female subjects of childbearing potential who are sexually active must be on an effective method of birth control for at least 1 month prior to Screening and agree to remain on birth control until completion of the study 5. Subject and/or legal guardian is capable of understanding and complying with the protocol requirements and is available for the duration of the study 6. Subject and/or legal guardian has been informed of the investigational nature of this study and has given voluntary written informed consent and, if appropriate, child/adolescent has provided ‘assent’ and Health Insurance Portability and Accountability Act (HIPAA) or patient protection authorization in accordance with institutional, local, and national personal health data protection guidelines< PRIMARY OUTCOME: Main Objective: •To evaluate the safety of two dose regimens of ferumoxytol [3.5 mg Fe/kg x 4 doses (max 255 mg/dose) and 7 mg Fe/kg x 2 doses (max 510 mg/dose)] compared with oral iron [2.5 mg/kg per dose twice daily (max 100 mg/dose) for 5 weeks]; •To evaluate the efficacy of ferumoxytol [cumulative dose of 14 mg Fe/kg; max. 1.02 g] compared with oral iron (max 100 mg/dose for 5 weeks) as assessed by changes in hemoglobin from Baseline to Week 5; Primary end point(s): PRIMARY ENDPOINT: Mean change in hemoglobin from Baseline to Week 5; ADDITIONAL EFFICACY ENDPOINTS:; Mean change in hemoglobin from Baseline to Week 7,; Proportion of subjects with an increase in hemoglobin =1.0 g/dL during the period from Baseline to Week 5 and Week 7,; Proportion of subjects with an increase in hemoglobin to =12.0 g/dL during the period from Baseline to Week 5 and to Week 7,; Mean change in TSAT from Baseline to Week 5 and Week 7,; Time to an increase in hemoglobin of =1.0 g/dL from Baseline,; Proportion of subjects requiring initiation of ESA or >20% increase in dose during the study,; Proportion of subjects receiving blood transfusions during the study,; Mean change in other markers of iron stores (eg, serum ferritin and serum iron) from Baseline to Week 5 and Week 7,; SAFETY ENDPOINTS:; Adverse events of special interest (AESI) (hypotension and hypersensitivity),; SAEs,; Severe AEs,; Cardiovascular AEs (nonfatal myocardial infarction, heart failure, moderate to severe hypertension, and hospitalization due to any cardiovascular cause),; AEs leading to study drug discontinuation,; All AEs, vital signs (blood pressure, heart rate, respiration rate) and body temperature, and routine laboratory parameters (hematology, chemistry, iron panel, and urinalysis).; PHARMACOKINETIC ENDPOINT:; Maximum concentration (Cmax),; Area under the curve (AUC), ; Half life (t1/2) Secondary Objective: •To determine the single dose PK profile of ferumoxytol (3.5 mg Fe/kg, max 255 mg/dose; 7.0 mg Fe/kg, max 510 mg/dose)