Ferric Citrate for Chronic Kidney Disease

(FIT4KID Trial)

Recruiting at 21 trial locations

Overseen By Barbara Gales, RN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must not be taking: Phosphate binders

Disqualifiers: Intestinal malabsorption, GI disorders, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 months

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

We will conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6-18 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 20 core clinical sites.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on growth hormone, calcitriol, nutritional vitamin D, iron, or erythropoiesis-stimulating agents, your doses must be stable for at least 2 weeks before joining. You cannot participate if you are currently treated with phosphate binders.

Is ferric citrate safe for humans?

Ferric citrate has been shown to be generally safe in humans, with studies reporting only mild gastrointestinal side effects. It has been tested in patients with chronic kidney disease and end-stage renal disease, demonstrating good tolerance and safety. ^{1 2 3 4 5}

How is the drug Ferric Citrate unique for treating chronic kidney disease?

Ferric Citrate is unique because it not only helps control high phosphate levels in the blood, which is common in chronic kidney disease, but also improves iron levels and reduces the need for additional iron and anemia treatments. This dual action makes it different from other treatments that typically address only one of these issues. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Ferric Citrate for chronic kidney disease?

Ferric citrate has been shown to effectively control serum phosphorus levels and improve iron parameters in patients with chronic kidney disease, particularly those on dialysis. It also reduces the need for intravenous iron and erythropoietin stimulating agents, which are used to manage anemia, while maintaining hemoglobin levels. ^{1 2 3 4 7}

Who Is on the Research Team?

Isidro Salusky, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for children aged 6-17 with moderate chronic kidney disease (stages 3-4) who have normal phosphate levels and can swallow tablets. They should be on stable doses of certain medications like growth hormone or iron supplements for at least two weeks before the study starts, and they must be able to eat at least two meals a day.

Inclusion Criteria

Your blood ferritin level is less than 500 ng/ml and your transferrin saturation (TSAT) is less than 50%.

Your kidney function, measured by GFR, is between 15-59 ml/min per 1.73 m2.

My blood phosphate levels are normal for my age.

Exclusion Criteria

Reinforce adherence

Administer the Medical Adherence Measure tool

Prepare one month's supply of drug and enter them into eCAP system

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a daily fixed weight-based dose of Ferric Citrate or placebo for 12 months

12 months

Visits at baseline, months 3, 6, 9, 12 (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ferric Citrate
• Placebo

Trial Overview The trial is testing if ferric citrate (FC) affects a hormone called iFGF23 in kids with kidney disease over a year. It's a double-blind study, meaning neither the participants nor the researchers know who gets FC or placebo. Kids are randomly chosen to get either FC or fake pills that look like FC.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

During the 12-month trial, participants will be given a fixed weight-based dose of Ferric Citrate (FC). The full medication dose will be 3g/day for participants weighing \<31 kg, 5g/day for those weighing \>31 - \<51 kg, and 6g/day for participants \>51 kg. These doses will be divided into three doses to be taken with meals.

Group II: Control Arm Placebo Group 1 Intervention

During the 12-month trial, participants will be given a fixed weight-based dose of Placebo. The full medication dose will be 3g/day for participants weighing \<31 kg, 5g/day for those weighing \>31 - \<51 kg, and 6g/day for participants \>51 kg. These doses will be divided into three doses to be taken with meals.

Ferric Citrate is already approved in United States for the following indications:

Approved in United States as Auryxia for:

• Hyperphosphatemia in patients with chronic kidney disease on dialysis
• Iron-deficiency anemia in patients with chronic kidney disease not on dialysis

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Ferric citrate (Zerenex™) has been confirmed as effective and safe in controlling serum phosphorus levels in patients with end-stage renal disease during Phase III trials.

In addition to managing hyperphosphatemia, ferric citrate improves iron levels and reduces the need for intravenous iron and erythropoietin, which may help in treating anemia related to end-stage renal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric citrate spans mineral metabolism and anemia domains in ESRD: a review of efficacy and safety data. Sinsakul, M., Rodby, R., Umanath, K., et al.[2015]

Ferric citrate is a new phosphate-binding agent that works by releasing ferric ions in the bowel to bind dietary phosphorus, which is then excreted, showing promise in treating patients with end-stage renal disease.

Current studies indicate that ferric citrate is effective and safe, with only mild gastrointestinal side effects, and an ongoing Phase III trial is further evaluating its safety and efficacy in dialysis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric citrate: a novel phosphate-binding agent. Umanath, K., Niecestro, R., Lewis, JB., et al.[2019]

Ferric citrate hydrate (JTT-751) effectively reduces phosphorus absorption in normal rats and increases fecal phosphorus excretion, indicating its potential as a treatment for hyperphosphatemia.

In chronic renal failure rats, JTT-751 significantly lowered serum phosphorus levels and prevented complications such as ectopic calcification, secondary hyperparathyroidism, and bone abnormalities, suggesting its efficacy in managing kidney disease-related phosphorus issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification. Iida, A., Kemmochi, Y., Kakimoto, K., et al.[2015]

Auryxia® (ferric citrate) is effective in managing chronic kidney disease (CKD) by lowering serum phosphate levels and improving iron deficiency anemia, making it a dual-purpose treatment for CKD patients.

Clinical studies have shown that Auryxia significantly reduces levels of fibroblast growth factor 23 (FGF23), a key risk factor for cardiovascular issues in CKD, although further long-term studies are needed to assess its cardiovascular effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of Action and Clinical Attributes of Auryxia&#174; (Ferric Citrate). Ganz, T., Bino, A., Salusky, IB.[2021]

Ferric citrate (Auryxia) is effective in treating hyperphosphatemia, a condition characterized by elevated phosphate levels in the blood, particularly in patients with chronic kidney disease.

The treatment works by binding phosphate in the gastrointestinal tract, reducing its absorption and helping to lower phosphate levels safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric citrate (auryxia) for the treatment of hyperphosphatemia. Pennoyer, A., Bridgeman, MB.[2020]

In a study involving 378 patients with chronic kidney disease (CKD) and iron-deficiency anemia (IDA), ferric citrate treatment showed similar effectiveness in increasing hemoglobin levels for patients with and without heart failure (HF), with 43% of HF patients responding positively to treatment.

While ferric citrate was generally safe, adverse events related to HF were more common in patients with HF, suggesting that while it can be used for IDA in CKD patients, careful monitoring is needed for those with concurrent heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of Oral Ferric Citrate in Patients With Iron-Deficiency Anemia and Chronic Kidney Disease With or Without Heart Failure. McCullough, PA., Uhlig, K., Neylan, JF., et al.[2019]

In a phase 3 study involving 90 nondialysis-dependent CKD patients, ferric citrate hydrate significantly reduced serum phosphate levels by an average of 1.29 mg/dl compared to a negligible change in the placebo group, demonstrating its efficacy as a phosphate binder.

Ferric citrate hydrate not only helped achieve target serum phosphate levels in 64.9% of patients but also lowered fibroblast growth factor-23 levels and increased serum iron parameters, indicating a beneficial effect on mineral metabolism in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD. Yokoyama, K., Hirakata, H., Akiba, T., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Ferric citrate spans mineral metabolism and anemia domains in ESRD: a review of efficacy and safety data. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Ferric citrate: a novel phosphate-binding agent. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification. [2015]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Mechanism of Action and Clinical Attributes of Auryxia&#174; (Ferric Citrate). [2021]

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

Ferric citrate (auryxia) for the treatment of hyperphosphatemia. [2020]

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

Usefulness of Oral Ferric Citrate in Patients With Iron-Deficiency Anemia and Chronic Kidney Disease With or Without Heart Failure. [2019]

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

Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD. [2022]