Ferric Derisomaltose for Iron Deficiency Anemia in Children

Overseen By Pharmacosmos A/S Clinical and Non-clinical Research

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Pharmacosmos A/S

Must not be taking: IV iron, Chemotherapy

Disqualifiers: Pregnancy, Iron overload, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Several clinical trials have been reported for ferric derisomaltose where it has been shown to be well tolerated and to improve markers of IDA. All clinical trials with ferric derisomaltose have been performed in adults, however, IDA is not specific to the adult population. In fact, children are likely to develop IDA due to their rapid growth. The aim in this trial is to evaluate the efficacy and safety of intravenous (IV) ferric derisomaltose in children 0 to \<18 years of age with IDA due to NDD-CKD or with IDA who are intolerant or unresponsive to oral iron . The subjects will receive ferric derisomaltose/iron isomaltoside 1000 (Monoferric®/Monofer®), at single doses of 10 mg/kg or 20 mg/kg with a maximal dose of 1000 mg. 24 subjects will be part of a PK assessment, meaning that more blood samples will be drawn within the first week after treatment. The blood samples will be used for analysis of the amount of total iron in the blood from treatment is given to day 7. For the individual subject, duration of the trial will be approximately 10 weeks (including a 14-day screening period) and each subject will attend 6-9 visits. Subjects who will be included in the PK assessments will attend 8 (subjects age 6 to \<12 years old and 0 to \<6 years old) or 9 (subjects age 12 to \<18 years old) visits, while the other subjects will attend 6 visits.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received IV iron within 10 days before screening or certain treatments like blood transfusions or chemotherapy within 30 days before screening.

What data supports the effectiveness of the drug Ferric Derisomaltose for treating iron deficiency anemia in children?

Research shows that Ferric Derisomaltose is effective in rapidly replenishing iron levels in patients with iron deficiency anemia, including those with chronic conditions like kidney disease and heart failure. It has been shown to improve symptoms such as fatigue and has a good safety profile with rare serious side effects. ^{1 2 3 4 5}

Is ferric derisomaltose safe for use in humans?

Ferric derisomaltose is generally safe for use in humans, with studies showing a low incidence of serious allergic reactions and cardiovascular events. It has been used safely in various conditions, including iron deficiency anemia and chronic kidney disease, with rare occurrences of severe side effects. ^{3 4 6 7 8}

How is the drug Ferric Derisomaltose different from other treatments for iron deficiency anemia in children?

Ferric Derisomaltose is unique because it can provide complete iron repletion in a single high-dose intravenous infusion, unlike other iron treatments that often require multiple doses. It also has a good safety profile with fewer side effects like hypophosphatemia (low phosphate levels in the blood) compared to other intravenous iron compounds. ^{2 3 4 5 9}

Eligibility Criteria

This trial is for children under 18 with Iron Deficiency Anemia (IDA) who haven't responded to or can't tolerate oral iron. It includes those with non-dialysis-dependent chronic kidney disease (NDD-CKD), provided they have specific blood test results and are not on certain treatments like IV iron, blood transfusions, or chemotherapy recently.

Inclusion Criteria

I am under 18 and have both my consent and child assent for trial participation.

I have iron deficiency anemia due to conditions like stomach issues or kidney disease.

I have a history of not responding well to oral iron treatments.

Exclusion Criteria

I am currently pregnant or nursing.

Your hemoglobin level is less than 5.0 grams per deciliter.

You had a bad allergic reaction to IV iron treatments in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive intravenous ferric derisomaltose at single doses of 10 mg/kg or 20 mg/kg

8 weeks

6-9 visits (in-person)

Pharmacokinetic Assessment

24 subjects undergo additional blood sampling for PK analysis within the first week after treatment

1 week

2-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Ferric Derisomaltose

Trial Overview The trial tests the safety and effectiveness of Ferric Derisomaltose, an intravenous iron treatment for IDA in kids. Participants will receive a single dose based on weight, up to a maximum of 1000 mg. Some will have additional blood tests to measure how much iron stays in their system over a week.

Participant Groups

Group I: Ferric Derisomaltose Experimental Treatment 1 Intervention

All subjects (a total of 200) will be treated with Ferric Derisomaltose. 12 subjects (half of the 24 subjects participating in the PK-part of the trial) will be treated with 10mg/kg while the remaining subjects will be treated with 20 mg/kg. .

Ferric Derisomaltose is already approved in United States, European Union for the following indications:

Approved in United States as Monoferric for:

• Iron deficiency anemia in adults with intolerance to oral iron or unsatisfactory response to oral iron or non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Approved in European Union as Monofer for:

• Iron deficiency anemia in adults with intolerance to oral iron or unsatisfactory response to oral iron or non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Who Is Running the Clinical Trial?

Pharmacosmos A/S

Lead Sponsor

Trials

45

Recruited

9,700+

Findings from Research

In a study of 72 children with iron deficiency anemia (IDA) who did not respond to oral iron, intravenous ferric carboxymaltose (FCM) significantly increased hemoglobin levels from a median of 9.1 g/dL to 12.3 g/dL within 4-12 weeks after infusion.

The treatment was found to be safe, with 84% of patients experiencing no adverse effects, and only minor transient complications reported in 7 infusions, indicating a favorable risk profile for FCM in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Who Respond Poorly to Oral Iron. Powers, JM., Shamoun, M., McCavit, TL., et al.[2018]

In a study involving 771 patients with heart failure and iron deficiency anemia, intravenous ferric derisomaltose (FDI) was associated with a reduction in recurrent hospitalizations for heart failure and cardiovascular death, suggesting it may improve patient outcomes.

Patients receiving FDI reported significant improvements in quality of life, particularly in physical health, indicating that FDI not only addresses iron deficiency but also enhances overall well-being in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of ferric derisomaltose on cardiovascular and non-cardiovascular events in patients with anemia, iron deficiency and heart failure with reduced ejection fraction. Ray, R., Ford, I., Cleland, JGF., et al.[2023]

Ferric derisomaltose is an effective intravenous iron treatment that allows for complete iron repletion in a single high-dose infusion, making it a rapid and cost-effective option for patients with iron deficiency.

It has a good safety profile, with rare occurrences of serious reactions like anaphylaxis and lower rates of hypophosphatemia compared to older intravenous iron formulations, indicating its suitability for a wide range of patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of ferric derisomaltose as a treatment for anemia. Kassianides, X., Bodington, R., Bhandari, S.[2021]

In a large study of 7354 patients receiving ferric derisomaltose (FDI) for iron deficiency, the incidence of adverse reactions was very low, with only 1.7% experiencing any reactions and less than 0.1% having anaphylaxis, indicating that FDI is a safe treatment option.

Significant improvements in hemoglobin and ferritin levels were observed by Month 4 post-infusion, particularly in patients from surgical specialties, suggesting that FDI is effective in increasing iron levels in diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of intravenous ferric derisomaltose evaluated through safety and efficacy reporting in the UK. Sinclair, RCF., Nadaraja, S., Kennedy, NA., et al.[2023]

High-dose intravenous ferric derisomaltose (Monofer®) infusions of 500 and 1000 mg effectively corrected iron deficiency and iron deficiency anemia in elderly patients, leading to rapid improvements in laboratory parameters and symptoms like fatigue.

Intravenous iron administration is a viable treatment option for patients who cannot tolerate oral iron or have poor absorption, potentially reducing morbidity and mortality associated with untreated iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients. Khiatani, D., Tay, HS., Cushway, TR.[2022]

Ferric derisomaltose (FDI) is a safe and effective treatment for iron deficiency anemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD), showing a lower rate of cardiovascular adverse events compared to iron sucrose (IS).

Patients receiving a single infusion of FDI experienced a faster hematological response, with significant improvements in hemoglobin and ferritin levels, compared to those receiving multiple doses of IS, regardless of their history of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravenous Ferric Derisomaltose Compared to Iron Sucrose for Iron Deficiency Anemia in Patients with Chronic Kidney Disease With and Without Heart Failure. Ambrosy, AP., von Haehling, S., Kalra, PR., et al.[2021]

Ferric derisomaltose (FDI) significantly increased hemoglobin levels in Japanese patients with iron-deficiency anemia (IDA) related to gastrointestinal diseases, with an average increase of 4.33 g/dL across all participants in a phase III study involving 40 patients.

The treatment was found to be safe, with 60% of patients experiencing treatment-emergent adverse events, but no serious or unexpected safety issues were reported, indicating a favorable safety profile for both intravenous bolus injection and drip infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose for iron-deficiency anemia associated with gastrointestinal diseases: a single-arm, randomized, uncontrolled, open-label study. Kawabata, H., Tamura, T., Tamai, S., et al.[2022]

In a trial involving 1512 patients with iron deficiency anemia, a single dose of 1000 mg iron isomaltoside (IIM) was found to be as safe as iron sucrose (IS), with very low rates of serious hypersensitivity reactions (0.3% for IIM vs 0.4% for IS).

IIM not only met the non-inferiority criteria for hemoglobin change but also resulted in a significantly faster hematological response within the first two weeks compared to IS, which requires multiple doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. Auerbach, M., Henry, D., Derman, RJ., et al.[2021]

Ferric derisomaltose (FDI) is effective for treating iron deficiency anemia in patients with non-dialysis-dependent chronic kidney disease (CKD) and those undergoing peritoneal dialysis, showing significant improvements in hemoglobin, transferrin saturation, and ferritin levels after administration.

The treatment was found to be safe, with only three adverse reactions reported among 52 infusions given to 35 patients, and a majority of Canadian renal pharmacists indicated that FDI is funded or available in their hospitals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis. England, E., Sheffield, M., Poyah, P., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Who Respond Poorly to Oral Iron. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

The impact of ferric derisomaltose on cardiovascular and non-cardiovascular events in patients with anemia, iron deficiency and heart failure with reduced ejection fraction. [2023]

3. England pubmed.ncbi.nlm.nih.gov

An evaluation of ferric derisomaltose as a treatment for anemia. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Real-world experience of intravenous ferric derisomaltose evaluated through safety and efficacy reporting in the UK. [2023]

5. Malaysia pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravenous Ferric Derisomaltose Compared to Iron Sucrose for Iron Deficiency Anemia in Patients with Chronic Kidney Disease With and Without Heart Failure. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose for iron-deficiency anemia associated with gastrointestinal diseases: a single-arm, randomized, uncontrolled, open-label study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. [2021]

9. Canada pubmed.ncbi.nlm.nih.gov

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis. [2023]