Multicenter Randomized Active-controlled Study to Investigate Efficacy & Safety of IV FCM in Pediatric Patients With IDA

Lead Sponsor: American Regent, Inc.

The primary objective of this study is to demonstrate the efficacy and safety of intravenous ferric carboxymaltose (FCM), compared to oral iron, in pediatric participants who have iron deficiency anemia.

This is a Phase III, multicenter, randomized, active-controlled study that compares the efficacy and safety of FCM to oral iron in pediatric participants with IDA and a documented history of an inadequate response to oral iron therapy at least 8 weeks (56 days) prior to randomization.

Participants who satisfy the inclusion requirements and no exclusion criteria will be eligible to participate in this study and enter into a screening phase to confirm eligibility. Randomization will occur via the Interactive Response Technology (IRT) system in a 1:1 ratio to either Group A, participants receiving FCM, or Group B, participants receiving oral iron (oral solution drops, elixir or oral tablets). Randomization will be stratified by baseline Hgb (<10, ≥10 g/dL) and age (1 to <12 years and ≥12 to 17 years).

The oral ferrous sulfate formulation received will be based on the participant's age, such that infants and children (1 to <4 years of age) will receive ferrous sulfate drops, children (≥4 to <12 years of age) will receive ferrous sulfate elixir, and adolescents (≥12 to 17 years of age) will receive ferrous sulfate tablets. Participants who experience adverse clinical symptoms due to the oral iron during the treatment phase may have a weight-based dose of ferrous sulfate reduced from 6 mg/kg to 3 mg/kg. If the participant is receiving tablets, the dose will be reduced from one tablet taken twice daily to one tablet per day.

Once randomized, all participants will return for efficacy and safety evaluations, including adverse events and laboratory assessments, on Days 7, 14, 28, and 35. Additional pharmacokinetic sampling and analyses will be performed for participants receiving FCM on Days 0 and 7.

• Iron Deficiency Anemia

Intervention Type: Drug

Intervention Name: Ferric carboxymaltose

Description: Intravenous iron

Arm Group Label: Ferric Caroboxymaltose

Intervention Type: Drug

Intervention Name: Ferrous Sulfate

Description: oral iron therapy

Arm Group Label: Oral Ferrous Sulfate

Other Name: oral iron

Criteria:

Inclusion Criteria:

1. Male or female participants 1 to 17 years of age with assent to participation and his/her parent or guardian is willing and able to sign the informed consent approved by the Independent Review Board / Ethics Committee.

2. Screening Hgb <11 g/dL.

3. Screening ferritin ≤300 ng/mL and transferrin saturation (TSAT) <30%.

4. Participants must have a documented history of an inadequate response to any oral iron therapy for at least 8 weeks (56 days) prior to randomization.

5. For participants who are receiving an erythropoietin stimulating agent (ESA): stable ESA therapy (+/- 20% of current dose) for at least 8 weeks prior to the qualifying screening visit and no ESA dosing or product changes anticipated for the length of the trial.

6. Participants undergoing treatment for inflammatory bowel disease (IBD) must be on stable therapy for at least 8 weeks prior to consent.

Exclusion Criteria:

1. Known history of hypersensitivity reaction to any component of FCM.

2. Previous randomization and treatment in this study or any other clinical study of FCM or VIT-45.

3. History of acquired iron overload, hemochromatosis, or other iron accumulation disorders.

4. Chronic kidney disease participants on hemodialysis.

5. History of significant diseases of the liver, hematopoietic system, cardiovascular system, psychiatric disorder, or other conditions which, on the opinion of the investigator, may place a subject at added risk for participation in the study.

6. Any existing non-viral infection.

7. Known history of positive hepatitis B antigen (HBsAg) or hepatitis C viral antibody (HCV) with evidence of active hepatitis.

8. Known history of positive HIV-1/HIV-2 antibodies (anti-HIV).

9. Anemia due to reasons other than iron deficiency (e.g., hemoglobinopathy and vitamin B12 or folic acid deficiency) that has not been corrected.

10. Intravenous iron and /or blood transfusion in the 4 weeks prior to consent.

11. Administration and / or use of an investigational product (drug or device) within 30 days of screening.

12. Alcohol or drug abuse within the past six months.

13. Female participant who is pregnant or lactating, or sexually active female who are of childbearing potential not willing to use an acceptable form of contraceptive precautions during the study.

14. Unable to comply with study procedures and assessments

Gender: All

Minimum Age: 1 Year

Maximum Age: 17 Years

Healthy Volunteers: No

Last Name: James Bambrick, BS

Phone: 6317723518

Phone Ext.: 61818

Email: [email protected]

United States

February 2020

Type: Sponsor

• Anemia
• Anemia, Iron-Deficiency

Label: Ferric Caroboxymaltose

Type: Active Comparator

Description: Ferric Carboxymaltose - 2 doses (day 0 and day 7) at 15 mg/kg to a maximum single dose of 750 mg (whichever is smaller) up to a maximum of total dose of 1500 mg administered as either an undiluted IV push at a rate of 100 mg (2mL)/minute OR in no more than 250 mL of normal saline and infused over 15 minutes.

Label: Oral Ferrous Sulfate

Type: Active Comparator

Description: Oral Ferrous Sulfate - will receive an age-dependent formulation of oral ferrous sulfate daily for 28 days as follows: participants <12 years of age will receive 6 mg (elemental iron)/kg/day divided into 2 daily doses of an oral liquid formulation, either drops or elixir, and participants ≥12 will receive 2 daily doses of oral tablets. Infants and children (ages 1 to <4 years) will receive oral ferrous sulfate drops, while children (ages ≥4 to <12 years) will receive oral ferrous sulfate elixir. Adolescents (ages ≥12 to 17 years) will receive an oral ferrous sulfate tablet (65 mg of elemental iron/tablet/dose) twice a day (BID). The maximum daily dose for all participants is 130 mg of elemental iron.

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)