Ferric Citrate for Chronic Kidney Disease

(FRONTIER Trial)

No longer recruiting at 20 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ferric citrate can help individuals with advanced chronic kidney disease (CKD) delay dialysis or reduce the risk of death. Participants will take either ferric citrate, an iron tablet, or a placebo, which looks like the treatment but contains no active ingredient, to compare outcomes. This study suits those with advanced CKD, a recent eGFR of 20 or less, not currently on dialysis, and specific iron levels in their blood. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that ferric citrate is likely to be safe for humans?

Research has shown that ferric citrate is generally safe for people with chronic kidney disease. It treats high phosphate levels in these patients and also helps with iron deficiency anemia. Studies have found that ferric citrate is well-tolerated, even with long-term use.

Some patients might experience mild side effects like an upset stomach or diarrhea, but these are uncommon and usually not serious. This study tests whether ferric citrate can delay the need for dialysis or lower the risk of death in people with advanced kidney disease. Since ferric citrate is already used for other kidney-related issues, it suggests a good safety record for these patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic kidney disease?

Unlike standard treatments for chronic kidney disease, which often focus on managing symptoms or slowing disease progression, ferric citrate offers a dual benefit by also addressing iron deficiency. Researchers are excited about ferric citrate because it not only helps manage phosphorus levels, a common issue in kidney disease, but also provides a source of iron to help combat anemia. This dual action makes it a promising option that could simplify treatment regimens for patients by tackling two problems with one medication.

What evidence suggests that ferric citrate might be an effective treatment for chronic kidney disease?

Research has shown that ferric citrate, which participants in this trial may receive, can help manage symptoms of chronic kidney disease (CKD). Studies have found that it controls phosphorus levels in the blood of CKD patients on dialysis, which is crucial for preventing bone and heart issues. Ferric citrate also treats iron deficiency anemia in CKD patients not on dialysis, increasing red blood cell counts and boosting energy. Additionally, ferric citrate acts as a phosphate binder, lowering high phosphate levels in the blood, a common problem in CKD. These findings suggest that ferric citrate could benefit patients with advanced CKD. ^{1 2 3 6 7}

Who Is on the Research Team?

Geoff Block, MD

Principal Investigator

USRC Kidney Research

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9203387/

Safety and effectiveness of ferric citrate hydrate in serum ... Ferric citrate hydrate (FC) is an oral iron-based phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease (CKD).

2. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1285012/full

Ferric citrate for the treatment of hyperphosphatemia and ... The application of ferric citrate therapy has yielded unexpected benefits in recent years for CKD patients suffering from hyperphosphatemia ...

3. auryxiahcp.com auryxiahcp.com/iron-deficiency-anemia/efficacy/

Efficacy | AURYXIA® (ferric citrate) tablets For HCPs This trial evaluated the efficacy and safety of AURYXIA for the treatment of iron deficiency anemia in adult patients with CKD not on dialysis.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05085275

NCT05085275 | Ferric Citrate for the Prevention of Renal ... A 9-month randomized, double-blind, placebo-controlled study to compare the effect of fixed dose ferric citrate versus placebo in patients with advanced ...

5. ir.akebia.com ir.akebia.com/news-releases/news-release-details/akebia-therapeutics-announces-positive-top-line-results-phase-4

Press Release AURYXIA® (ferric citrate) is indicated for: The control of serum phosphorus levels in adult patients with chronic kidney disease on dialysis ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35258721/

Safety and effectiveness of ferric citrate hydrate in serum ... Ferric citrate hydrate (FC) is an oral iron-based phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease (CKD).

7. ajkd.org ajkd.org/article/S0272-6386(14)01357-2/fulltext

A 12-Week, Double-Blind, Placebo-Controlled Trial of ... These results demonstrate that short-term use of ferric citrate effectively repleted iron stores, increased hemoglobin levels, and reduced serum phosphate and ...