Ferric Citrate for Chronic Kidney Disease

(FRONTIER Trial)

Recruiting at 19 trial locations

Overseen By Mary Mouracade, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: USRC Kidney Research

Disqualifiers: Acute kidney injury, Iron overload, Active malignancy, others

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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

289 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an iron supplement in patients with severe kidney disease who are not yet on dialysis. The aim is to see if it can delay dialysis or reduce death risk. Participants will take the supplement with meals and be monitored over several months. The supplement has been shown to effectively manage certain health markers in patients with chronic kidney disease.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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 5}

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 6}

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 7}

Research Team

Geoff Block, MD

Principal Investigator

USRC Kidney Research

Eligibility Criteria

Adults over 18 with advanced chronic kidney disease (eGFR ≤20 ml/min/1.73m2), high phosphate levels, and iron deficiency can join this trial. They must not be pregnant or planning pregnancy, have a life expectancy of more than 6 months, and no recent drug abuse or hypersensitivity to oral iron therapy.

Inclusion Criteria

Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure

Women who could become pregnant must have a negative pregnancy test within 28 days before starting the study.

My kidney function is severely reduced, with an eGFR of 20 ml/min/1.73m2 or less.

Exclusion Criteria

I am currently taking antibiotics for an active infection.

Use of an investigational medication or participation in an investigational study within 30 days prior to Day 1

I am expected to start regular dialysis soon, within the next 8 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ferric citrate or placebo for 9 months to assess the effect on time to initiation of maintenance dialysis or all-cause mortality

9 months

Routine scheduled clinical encounters

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ferric Citrate
• Placebo

Trial Overview The study tests if ferric citrate tablets can prevent renal failure better than a placebo in adults with severe chronic kidney disease. It's a randomized, double-blind trial lasting for 9 months to see if it delays the need for dialysis or impacts mortality.

Participant Groups

Group I: Ferric citrate Experimental Treatment 1 Intervention

Supplied as tablets for oral administration containing 1 gram ferric citrate (210 milligrams of ferric iron). Administered orally with meals or snacks.

Group II: Placebo Placebo Group 1 Intervention

Tablets, matching in color and size to ferric citrate.

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?

USRC Kidney Research

Lead Sponsor

Trials

5

Recruited

3,000+

Akebia Therapeutics

Industry Sponsor

Trials

35

Recruited

12,400+

Findings from Research

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 (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]

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® (Ferric Citrate). Ganz, T., Bino, A., Salusky, IB.[2021]

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]

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]

References

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

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

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

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate). [2021]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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]