Dose Ranging Study of Dialysate Containing Soluble Iron to Treat Subjects With End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Dialysate containing soluble iron (Soluble Ferric Pyrophosphate) is safe and effective in maintaining physiological iron levels during chronic hemodialysis.

Detailed Description
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The study was designed to evaluate the efficacy of SFP-containing dialysate solution in maintaining physiological iron levels during chronic hemodialysis, as measured by the primary endpoint of the percent of patients whose Hemoglobin (Hgb) decreased by at least 1.0 gram/ deciliter (g/dL) from baseline. The efficacy and safety findings are to be used to determine the optimal concentration of SFP needed to safely maintain iron levels, compensating for iron losses during chronic hemodialysis.

Official Title
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A Dose Ranging Study of Dialysate Containing Soluble Ferric Pyrophosphate (SFP) Versus Control in Subjects With ESRD Receiving Chronic Hemodialysis.

Conditions
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End-Stage Renal Disease (ESRD)

Intervention / Treatment
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* Device: Standard Bicarbonate Solution
* Drug: Soluble Ferric Pyrophosphate
* Drug: Soluble Ferric Pyrophosphate
* Drug: Soluble Ferric Pyrophosphate
* Drug: Soluble Ferric Pyrophosphate


Participation Criteria
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Eligibility Criteria
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Selected Inclusion Criteria: Adult subject ≥ 18 years of age undergoing chronic hemodialysis for end-stage renal disease (ESRD) three times a week Hemoglobin (Hgb) values on two successive screening/baseline measures immediately prior to the start of the study averaging 10.1 to 11.5 grams/ deciliter (g/dL), inclusive Transferrin Saturation (TSAT) values that average 20% or more, but not exceeding 35%, prior to dialysis measured during the screening period Ferritin values that average 200 to 800 micrograms/ liter (µg/L), inclusive, measured during the screening period. An average ferritin above 800 µg/L but no greater than 1200 µg/L is allowed if the average TSAT is 20% to no greater than 25%. Except for vascular access surgery, subject has no hospitalization in previous three months for a significant illness that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of the study. No blood transfusions within the last 4 weeks are allowed. Subject has an adequate dialyzer blood flow rate that is acceptable to the Principal Investigator Exclusion Criteria: Hemoglobin (Hgb) values on two successive baseline/screening measurements that average ≥ 11.6g/dL Subject with a current malignancy involving a site other than skin Subject with a history of drug or alcohol abuse within the last six months Subject believed to be unable to complete the entire study (e.g., due to a concurrent disease, life expectancy of less than a year) Subject who the Principal Investigator considers will be placed at increased risk by the study procedures Subject requiring hemodialysis more than 3 times per week on a regular basis. Subject who is unable to discontinue oral iron or intravenous iron supplements for the duration of the study Subject who is pregnant Subject considered incompetent to give an informed consent Subject with a positive test for Hepatitis B Surface Antigen within the past 30 days or during screening Subject with known HIV infection (if this is not known, no HIV testing will be performed) Subject with cirrhosis of the liver based on histological criteria or clinical criteria (presence of ascites, esophageal varices, spider nevi, or history of hepatic encephalopathy). Subject with hepatitis C, in the absence of cirrhosis, is not excluded from participation in the study if ALT and AST levels are below 2 times the upper limit of normal consistently during the 2 months preceding enrollment Subject with active tuberculosis, fungal, viral, or parasitic infection Subject with active bacterial infection requiring antibiotic therapy Subject with pre-dialysis Corrected Q-wave to T-wave (QTc) interval ≥ 470 milliseconds (ms) Subject with a history of hypokalemia, decompensated heart failure, or family history of Long QT Syndrome that in the Investigator's judgment poses a risk for Torsades de Pointe during the study Subject using concomitant medications known to prolong QT/QTc interval (See Appendix I, TABLE A) Subject receiving more than 60,000 units or 120 micrograms of erythropoietin (Epogen®, Procrit®, or Aranesp®) per week Subject has participated in another clinical trial within 30 days of signing Informed Consent

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 0 µg iron/dL of dialysate<br>Placebo 0 micrograms (µg) of iron/ deciliter (dL) of dialysate | Device: Standard Bicarbonate Solution<br>* Patients received 0 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.<br>* Other names: Placebo;|
| Experimental: 5 µg iron/dL of dialysate<br>5 micrograms (µg) of iron/ deciliter (dL) of dialysate | Drug: Soluble Ferric Pyrophosphate<br>* Patients received 5 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.<br>* Other names: SFP;|
| Experimental: 10 µg iron/dL of dialysate<br>10 micrograms (µg) of iron/ deciliter (dL) of dialysate | Drug: Soluble Ferric Pyrophosphate<br>* Patients received 10 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.<br>* Other names: SFP;|
| Experimental: 12 µg iron/dL of dialysate<br>12 micrograms (µg) of iron/ deciliter (dL) of dialysate | Drug: Soluble Ferric Pyrophosphate<br>* Patients received 12 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.<br>* Other names: SFP;|
| Experimental: 15 µg iron/dL of dialysate<br>15 micrograms (µg) of iron/ deciliter (dL) of dialysate | Drug: Soluble Ferric Pyrophosphate<br>* Patients received 15 micrograms (µg) of iron/ decilited (dL) of dialysate during dialysis 3 times/week for up to 26 weeks.<br>* Other names: SFP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects Whose Hemoglobin (Hgb) Decreases by a Total of 1.0 Grams/ Deciliter (g/dL) (or More) From Baseline on Each of Two Successive Measurements. | Efficacy of a Soluble Ferric Pyrophosphate (SFP)-containing dialysate solution in maintaining physiological iron levels during chronic HD, as measured by the percent of subjects whose hgb decreases by a total of 1.0 g/dL (or more) from baseline on each of two successive measurements. Hemoglobin was obtained weekly at the mid-week dialysis treatments and compared to baseline value (average of two hgb measurements obtained at the two consecutive baseline visits prior to randomization). | up to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin (Hgb) |  | two time points: baseline and final evaluation (last post baseline assessment, up to 26 weeks) | 
| Time in Days for Hgb to Decrease by a Total of > = 1.0 g/dL From Baseline on Each of Two Successive Measurements in Each Treatment Group. | Kaplan-Meier Estimate of Time to First Hgb Decrease by >= 1.0 g/dL | Up to 26 weeks | 
| Reticulocyte Hemoglobin (CHr) Values Every Four Weeks, and at the End of the Subject's Treatment. | Efficacy of SFP administration in dialysate solution as measured by Chr values every four weeks, and at the end of the Subject's Treatment (up to 26 weeks). | Every 4 weeks | 
| Number of Subjects With Infection Episodes Requiring Antibiotic or Anti-fungal Therapy in Each Treatment Group. |  | At each dialysis session for up to 26 weeks | 
| Number of Subjects With a Rise in Hemoglobin (Hgb) to 12.6 g/dL or More on Two Separate Occasions Measured One Week Apart. |  | two separate sessions measured one week apart. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subjects with ESRD receiving chronic Hemodialysis