A 58-Week Safety and Efficacy Trial of Ferric Citrate in Patients With ESRD on Dialysis

Study Overview
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Brief Summary
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This is up to a 58 week study comparing ferric citrate to active control for 52 weeks in ESRD dialysis patients, and subsequently comparing ferric citrate to placebo for 4 weeks.

Detailed Description
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This trial is a three-period, multicenter, safety and efficacy clinical trial. The first period is a two-week Washout Period, the second period is a 52-week randomized, open-label, active control Safety Assessment Period, and the third period is a four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period in only the patients who were randomized to treatment with ferric citrate during the Safety Assessment Period. The primary objectives of this trial are to determine the long-term safety over 52 weeks of up to twelve (12) caplets/day of KRX-0502 (ferric citrate) in patients with ESRD undergoing either hemodialysis or peritoneal dialysis and to determine the efficacy of KRX-0502 (ferric citrate) in the four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period.

Official Title
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A Three-Period, 58-Week Safety and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD) on Dialysis

Conditions
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Hyperphosphatemia, Kidney Failure

Intervention / Treatment
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* Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or non-pregnant, non-breast-feeding females Age ≥18 years On thrice-weekly hemodialysis or on peritoneal dialysis for at least the previous three months prior to Screening Serum phosphorus ≥6.0 mg/dL for study entry Taking less than 3-18 pills/day of current phosphate binder Willing to be discontinued from current phosphate binder(s) and initiated on ferric citrate Willing and able to give informed consent Life expectancy >1 year Exclusion Criteria: Parathyroidectomy within six months prior to Screening Actively symptomatic gastrointestinal bleeding or inflammatory bowel disease History of multiple drug allergies or intolerances History of malignancy in the last five years (treated cervical or non-melanomatous skin cancer may be permitted if approved by CCC) Previous intolerance to oral ferric citrate Intolerance to oral iron-containing products Psychiatric disorder that interferes with the patient's ability to comply with the study protocol Inability to tolerate oral drug intake Intolerance to calcium acetate and sevelamer carbonate Any other medical condition that renders the patient unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the patient Receipt of any investigational drug within 30 days of Screening Visit (Visit 0) Inability to cooperate with study personnel or history of noncompliance Unsuitable for this trial per Investigator's clinical judgment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Control<br>PhosLo (calcium acetate) Renvela (sevelamer carbonate) | Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo<br>* All intervention doses will be based on serum phosphorus levels and/or drug label requirements<br>* Other names: Zerenex;|
| Placebo Comparator: Placebo<br>Placebo | Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo<br>* All intervention doses will be based on serum phosphorus levels and/or drug label requirements<br>* Other names: Zerenex;|
| Experimental: KRX-0502 (Ferric Citrate)<br>ferric citrate | Drug: ferric citrate, ca acetate, sevelamer carbonate, placebo<br>* All intervention doses will be based on serum phosphorus levels and/or drug label requirements<br>* Other names: Zerenex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Serum Phosphorus From Baseline (Week 52) to the End of the Efficacy Assessment Period (EAP; Week 56) | Patients who completed the 52-week Safety Assessment Period (SAP) on KRX-0502 (ferric citrate) were randomized in a 1:1 ratio to receive either KRX-0502 (ferric citrate) or Placebo for 4 weeks. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Serum Ferritin From Baseline to Week 52 |  | 52 weeks | 
| Change in Mean Serum Transferrin Saturation (TSAT) From Baseline to the End of the Safety Assessment Period (Week 52) |  | 52 weeks | 
| IV Iron Analysis | Full Analysis Population, cumulative IV Iron administration from Baseline to the end of the Safety Assessment Period (Week 52) | 52 weeks | 
| ESA Analysis | Full analysis population, cumulative Erythropoiesis-stimulating agent (ESA) administration from baseline to the end of the Safety Assessment Period (Week 52) | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESRD, end-stage renal disease, dialysis, hemodialysis, peritoneal dialysis, hemodialysis (HD), peritoneal dialysis (PD), chronic renal insufficiency, phosphate binder, kidney failure, renal failure