Research study to evaluate the experimental drug ferumoxytol, to see how well it works for children with chronic kidney disease (CKD) and iron deficiency anemia (IDA) or who are at risk of developing IDA, and to see how safe it is compared to another marketed iron product – iron sucrose

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amag Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

25 Jun 2018 → ongoing

Decision date (initial)

2024-09-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AMAG Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-516263-92-00

EudraCT number

2017-004026-15

ClinicalTrials.gov

NCT03619850

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

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.

Secondary objectives 1

1. To determine the single-dose PK and PD profile of ferumoxytol (7.0 mg Fe/kg, max 510 mg/dose) in pediatric subjects.

Conditions and MedDRA coding

Iron Deficiency Anemia (IDA) in Pediatric Subjects with Chronic Kidney Disease (CKD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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.

Exclusion criteria 15

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 (e.g., 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 (e.g., 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 16

1. 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.
2. 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.
3. Proportion of patients achieving a TSAT increase of at least 10% during the period from Baseline to Week 5.
4. Change in hemoglobin from Baseline to Week 5.
5. Whether or not the subject had an increase in hemoglobin ≥1.0 g/dL during the period from Baseline to Week 5.
6. Change in TSAT from Baseline to Week 5.
7. Whether or not the subject required initiation of ESA or a >20% increase in dose during the study.
8. Whether or not the subject received blood transfusions during the study.
9. Change in other markers of iron stores (e.g., serum ferritin and serum iron) from Baseline to Week 5.
10. Safety Endpoints: Incidence of adverse events of special interest (AESI) (hypotension and hypersensitivity).
11. Incidence of SAEs.
12. Incidence of Severe AEs.
13. Incidence of Cardiovascular AEs (myocardial infarction, heart failure, moderate to severe hypertension, and hospitalization due to any cardiovascular cause).
14. Incidence of AEs leading to study drug discontinuation.
15. Incidence of treatment emergent AEs.
16. Change in vital signs (blood pressure, heart rate, respiration rate) and body temperature, and routine laboratory parameters (hematology, chemistry, and iron panel).

Secondary endpoints 3

1. Pharmacokinetic Endpoints: Area Under the Curve (AUC).
2. Clearance
3. Distribution and elimination half-lives.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amag Pharmaceuticals Inc.

Sponsor organisation

Amag Pharmaceuticals Inc.

Address

1100 Winter Street Floor 2

City

Waltham

Postcode

02451-1427

Country

United States

Scientific contact point

Organisation

Amag Pharmaceuticals Inc.

Contact name

Medical Information

Public contact point

Organisation

Amag Pharmaceuticals Inc.

Contact name

Medical Information

Third parties 2

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications