E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dialysis dependent Chronic Kidney Disease |
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E.1.1.1 | Medical condition in easily understood language |
kidney disease that requires dialysis |
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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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 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
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E.2.2 | Secondary objectives of the trial |
•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) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female 6 months to <18 years of age
2.On peritoneal dialysis or hemodialysis for ≥3 months prior to Screening
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 one 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 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
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E.4 | Principal exclusion criteria |
1.History of allergy to either oral or IV iron
2.Allergy to two or more classes of drugs
3.Hemoglobin ≤7.0 g/dL
4.Serum ferritin level >600 ng/mL
5.Parenteral iron therapy within 4 weeks prior to Screening; oral iron therapy within 2 weeks prior to Screening; or RBC or whole blood transfusion within 2 weeks prior to Screening, or planned during the study
6.Erythropoiesis-stimulating agent therapy initiated, stopped, or dose changed by >20% within 4 weeks prior to Screening, or an anticipated ESA dose change of >20% during the study
7.Known causes of anemia other than iron deficiency (eg, vitamin B12 or folate deficiency, etc)
8.Major surgery or invasive intervention within 4 weeks prior to Screening, organ transplant within 6 months prior to Screening, or any planned surgery or intervention during the course of the study
9.Active malignancy within 2 years (except nonmelanoma skin cancer or carcinoma in situ that has been excised)
10.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
11.Female subjects who are pregnant or intend to become pregnant, or are breastfeeding, are within three months postpartum, or have a positive serum pregnancy test
12.Any other clinically significant medical disease or condition (eg, uncontrolled hypertension) 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) |
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 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 RBC or whole blood transfusions during the study,
Mean change in markers of iron stores (eg, serum ferritin, TSAT, 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, serum chemistry, and iron panel)
PHARMACOKINETIC ENDPOINTS:
Maximum concentration (Cmax),
Area under the curve (AUC),
Half-life (t1/2). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Proportion of subjects with an increase in hemoglobin ≥1.0 g/dL during the period from Baseline; Proportion of subjects with an increase in hemoglobin to ≥12.0 g/dL during the period from Baseline; Mean change in TSAT from Baseline; 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 5 and 7 post initial dose |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
France |
Germany |
Hungary |
Italy |
Lithuania |
Mexico |
Peru |
Poland |
Romania |
Russian Federation |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |