E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Iron Deficiency Anemia (IDA) in Pediatric Subjects with Chronic Kidney Disease (CKD) |
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E.1.1.1 | Medical condition in easily understood language |
Iron Deficiency Anemia (IDA) in Pediatric Subjects with Chronic Kidney Disease (CKD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022974 |
E.1.2 | Term | Iron deficiency anemia |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety (compared to iron sucrose) and efficacy of ferumoxytol (7.0 mg Fe/kg x 2 [max 510 mg/dose]) in pediatric CKD subjects with iron deficiency anemia (IDA) or who are at risk of development of IDA. |
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E.2.2 | Secondary objectives of the trial |
To determine the single-dose PK and PD profile of ferumoxytol (7.0 mg Fe/kg, max 510 mg/dose) in pediatric subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female 2 years to <18 years of age at time of consent
2. Has IDA defined as: a) hemoglobin <12.0 g/dL and b) with either 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
3. Has Chronic Kidney Disease defined as one of the following:
a. on chronic hemodialysis;
b. receiving chronic peritoneal dialysis;
c. eGFR of <60 mL/min/1.73 m2;
d. 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
4. 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
5. 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
6. Subject and/or legal guardian is capable of understanding and complying with the protocol requirements and is available for the duration of the study
7. 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, the child/adolescent has provided ‘assent’ and Health Insurance Portability and Accountability Act (HIPAA) or patient protection authorization had been adhered to in accordance with institutional, local, and national personal health data protection guidelines
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity reaction to any component of ferumoxytol and iron sucrose
2. History of allergy to intravenous (IV) iron
3. History of multiple drug allergies (>2)
4. Low systolic blood pressure (Age 1-9 years <70 + [age in years x 2] mmHg, Age 10-17 years <90 mmHg)
5. Hemoglobin ≤7.0 g/dL
6. Serum ferritin level >600 ng/mL
7. Parenteral iron therapy within 4 weeks prior to Day 1 Dosing; or blood transfusion within 4 weeks prior to Day 1 Dosing or planned at the time of Screening
8. Erythropoiesis-stimulating agent (ESA) therapy initiated, stopped or dose changed by >25% within 4 weeks prior to Screening, or anticipated ESA dose change of >20% during the study
9. Known causes of anemia other than iron deficiency (eg, vitamin B12 or folate deficiency, hemolytic anemia, etc)
10. Major surgery or invasive intervention within 4 weeks prior to Screening, or any planned major surgery or intervention during the course of the study
11. Active malignancy within 2 years prior to Screening (except non-melanoma skin cancer or carcinoma in situ that has been excised)
12. Active clinically significant infection (eg, systemic bacterial infection) or acute serious medical illness requiring treatment or intervention within 2 weeks prior to Screening
13. Received another investigational agent within 4 weeks prior to Screening, or planned receipt of an investigational agent not specified by this protocol during the study period
14. Female subjects who are pregnant or intend to become pregnant, or are breastfeeding, are within 3 months postpartum, or have a positive pregnancy test
15. Any other clinically significant medical or psychiatric disease or condition or subject responsibility that, in the Investigator’s opinion, may interfere with a subject’s (and/or legal guardian’s) ability to adhere to the protocol, interfere with assessment of the investigational product, or serve as a contraindication to the subject’s participation in the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints:
● Primary endpoint: Proportion of patients achieving a hemoglobin increase of at least 0.5 g/dL during the period from Baseline to Week 5
● Proportion of patients achieving a hemoglobin increase of at least 0.5 g/dL or TSAT increase of at least 10% during the period from Baseline to Week 5
● Proportion of patients achieving a TSAT increase of at least 10% during the period from Baseline to Week 5
● Change in hemoglobin from Baseline to Week 5
●Whether or not the subject had an increase in hemoglobin ≥1.0 g/dL during the period from Baseline to Week 5
● Change in TSAT from Baseline to Week 5
● Whether or not the subject required initiation of ESA or a >20% increase in dose during the study
● Whether or not the subject received blood transfusions during the study
● Change in other markers of iron stores (e.g., serum ferritin and serum iron) from Baseline to Week 5
Safety Endpoints:
● Incidence of adverse events of special interest (AESI) (hypotension and hypersensitivity)
● Incidence of SAEs
● Incidence of Severe AEs
● Incidence of Cardiovascular AEs (myocardial infarction, heart failure, moderate to severe hypertension, and hospitalization due to any cardiovascular cause)
● Incidence of AEs leading to study drug discontinuation
● Incidence of treatment emergent AEs
● Change in vital signs (blood pressure, heart rate, respiration rate) and body temperature, and routine laboratory parameters (hematology, chemistry, and iron panel) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints: Week 5
Safety endpoints: ongoing during the study duration |
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E.5.2 | Secondary end point(s) |
Pharmacokinetic Endpoints:
• Area Under the Curve (AUC)
• Clearance
• Distribution and elimination half-lives
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood samples for PK will be collected 10 minutes prior to administering the first dose; at 18 minutes (not before infusion ends and no later than 10 minutes after infusion ends), 1 hour (±15 minutes), 3 hours (±30 minutes), 5 hours (±30 minutes), 24 hours (±2 hours) and 48 hours (±4 hours) post the start of the infusion |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Mexico |
United States |
Lithuania |
Poland |
Hungary |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 3 |