Continuous Soluble Ferric Pyrophosphate (SFP) Iron Delivery Via Dialysate in Hemodialysis Patients

Phase 3

Completed

Conditions: Renal Failure Chronic Requiring Hemodialysis

Interventions: Drug: Soluble Ferric Pyrophosphate (SFP)
Device: Standard dialysate

Registration Number: NCT01320202

Lead Sponsor: Rockwell Medical Technologies, Inc.

Brief Summary: The purpose of this study is to confirm the safety and efficacy of Soluble Ferric Pyrophosphate (SFP) dialysate solution in maintaining iron delivery for erythropoiesis in anemic adult patients with chronic kidney disease (CKD) receiving hemodialysis. Efficacy will be measured primarily by the change from baseline in hemoglobin (Hgb).

Detailed Description: Screening: 2-3 weeks prior to enrollment in Stage 1.

Stage 1 (Run-In): 1-4 weeks depending on qualification for Stage 2.

Stage 2 (Randomized Blinded Treatment): 12 months unless withdrawn prematurely.

Stage 3 (Open-Label Treatment): The duration of Stage 2 plus Stage 3 is intended to be 18 months regardless of treatment assignment in Stage 2.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 305

Inclusion Criteria

Adult subject ≥ 18 years of age undergoing chronic hemodialysis three or four times per week for chronic kidney disease (CKD) for at least 4 months, and expected to remain on hemodialysis three to four times weekly and be able to complete the duration of the study.
Received IV iron therapy between 6 months and 2 weeks prior to enrollment in order to replace iron losses resulting from hemodialysis procedure.
Mean Screening Hgb ≥ 9.5 to ≤ 11.5 grams per deciliter (g/dL).
Mean Screening Transferrin Saturation (TSAT) ≥ 15% to ≤ 40%.
Mean Screening serum ferritin ≥ 200 to ≤ 800 micrograms per liter (µg/L).
If being administered epoetin, darbepoetin, or CERA, epoetin dose ≤ 45,000 Units (U)/week, darbepoetin dose ≤ 200 micrograms (µg)/week, or CERA dose ≤ 400 micrograms (µg)/month during the four weeks prior to enrollment.

Main

Exclusion Criteria

Patient has living kidney donor identified or living-donor kidney transplant scheduled. (Note: Patients awaiting deceased-donor transplant need not be excluded.)
Vascular access for dialysis with femoral catheter or non-tunneled catheter.
Received a total of > 800 milligrams (mg) IV iron during the 8 weeks prior to enrollment
If being administered an ESA, route of administration change or ESA dose change > 35% (i.e., [max - min dose]/max dose > 0.35) over the 2 weeks prior to screening.
Serum albumin < 3.0 grams per deciliter (g/dL) any time over the 8 weeks prior to enrollment.
Red Blood Cell (RBC) or whole blood transfusion within 12 weeks prior to enrollment.

Stage 2:

Main Inclusion Criteria:

Patient currently enrolled in the Stage 1 run-in period of study.
Undergoing chronic hemodialysis three or four times per week for chronic kidney disease (CKD), and expected to remain on hemodialysis three to four times weekly and be able to complete duration of the study.
Mean Hgb ≥ 9.5 to ≤ 11.5 g/dL over the three most recent consecutive every-week measurements prior to randomization.
Stable Hgb defined as ≤ 1.0 g/dL difference between the maximum and minimum Hgb values over the 3 weeks immediately prior to randomization.
Mean TSAT ≥ 15% to ≤ 40% over the two most recent consecutive every-other-week measurements prior to randomization.
Mean serum ferritin ≥ 200 to ≤ 800 µg/L over the two most recent consecutive every-other-week measurements prior to randomization.
If being administered epoetin, darbepoetin, or CERA, epoetin dose ≤ 45,000 U/week, darbepoetin dose ≤ 200 µg/week, or CERA dose ≤ 400 µg/month during the four weeks prior to randomization.

Main Exclusion Criteria:

Patient has living kidney donor identified or living-donor kidney transplant scheduled. (Note: Patients awaiting deceased-donor transplant need not be excluded.)
Vascular access for dialysis with femoral catheter or non-tunneled catheter.
Received any amount of IV iron during the 4 weeks prior to randomization.
If being administered an (Erythropoietin Stimulating Agent) ESA, change in dose over the 6 weeks immediately prior to randomization.
Serum albumin < 3.0 g/dL any time over the 8 weeks prior to randomization.
RBC or whole blood transfusion during Stage 1.

Stage 3:

Main Inclusion Criteria:

Patient randomized in Stage 2 who has completed the full duration of Stage 2 and less than 4 weeks have elapsed since completion of Stage 2, OR
Patient in Stage 2 who has been prematurely withdrawn from Stage 2 for protocol-defined Protocol-Mandated Change in Anemia Management and less than 4 weeks have elapsed since withdrawal from Stage 2, OR
Patient in Stage 2 who has been prematurely withdrawn from Stage 2 for Hgb >11.5 g/dL over ≥ 1 week confirmed by ≥ 2 consecutive measurements AND an associated increase in Hgb by ≥ 1 g/dL over 4 weeks.

Main Exclusion Criteria:

Patient in Stage 2 who has been prematurely withdrawn from Stage 2 for any reason other than as noted in inclusion criteria above.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Soluble Ferric Pyrophosphate (SFP) in dialysate	Soluble Ferric Pyrophosphate (SFP)	11 micrograms (µg) of iron / deciliter (dL) of dialysate.
Standard Dialysate	Standard dialysate	0 micrograms (µg) of iron / deciliter (dL) of dialysate.

Primary Outcome Measures

Name	Time	Method
Change From Baseline Hemoglobin at End-of-Treatment: Least-Squares Mean	Hgb measured weekly; up to 48 weeks from the date of randomization	Mean change from baseline Hgb (the average of the three most recent Hgb values preceding randomization) assessments during the last one-sixth of the treatment period for patients who prematurely withdraw from study treatment, but will include a minimum of at least the last two Hgb values. Value is expressed as least-squares mean with standard error.
Change From Baseline Hemoglobin at End-of-Treatment: Mean Baseline and End-of-Treatment Hgb	Hgb measured weekly; up to 48 weeks from the date of randomization	Mean change from baseline Hgb (the average of the three most recent Hgb values preceding randomization) assessments during the last one-sixth of the treatment period for patients who prematurely withdraw from study treatment, but will include a minimum of at least the last two Hgb values. Values expressed are mean baseline and end-of-treatment Hgb, along with the mean difference (standard deviation).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr)	Up to 48 weeks from the date of randomization	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Reticulocyte Hemoglobin Content (CHr) will be quantified.
Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Unsaturated Iron-Binding Capacity (UIBC), Serum Iron, and Total Iron-Binding Capacity (TIBC)	Up to 48 weeks from the date of randomization	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Unsaturated Iron-Binding Capacity (UIBC), Pre-Dialysis Serum Iron, and Pre-Dialysis Total Iron-Binding Capacity (TIBC) will be quantified.
Variability of Hemoglobin Concentration: Temporal Trend	Hgb measured weekly; up to 48 weeks from the date of randomization	The mean temporal trend of hemoglobin concentration value changes, as measured weekly from baseline until the end of participation in Stage 2.
Mean Change in Serum Iron From Pre-dialysis to Post-dialysis.	Up to 48 weeks from the date of randomization	The mean difference between the pre-dialysis and post-dialysis serum iron was calculated, using all post-baseline values obtained during Stage 2. Subjects could participate in Stage 2 for up to 48 weeks, provided that they did not complete Stage 2 early due to a protocol-mandated change in anemia management or withdraw from the study entirely for other reasons.
Change From Baseline to End-of-Treatment (EoT) in Ferritin	Up to 48 weeks from the date of randomization	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Ferritin will be quantified.
Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin	Up to 48 weeks from the date of randomization	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin will be quantified.
Red Blood Cell or Whole Blood Transfusion: Number of Patients Receiving Transfusion	up to 48 weeks from the date of randomization	The number of patients requiring red blood cell or whole blood transfusion while in the randomized treatment stage (Stage 2). Patients remained in Stage 2 until they met protocol-defined criteria for Stage 2 completion or until they had participated in Stage 2 for 48 weeks (whichever came sooner). If a patient was transfused, they were withdrawn from Stage 2.
Mean Change in TSAT (Transferrin) From Pre-dialysis to Post-dialysis.	Up to 48 weeks from the date of randomization	The mean difference between the pre-dialysis and post-dialysis TSAT (transferrin) was calculated, using all post-baseline values obtained during Stage 2. Subjects could participate in Stage 2 for up to 48 weeks, provided that they did not complete Stage 2 early due to a protocol-mandated change in anemia management or withdraw from the study entirely for other reasons.
Mean Change in Unsaturated Iron Binding Capacity (UIBC) From Pre- to Post-dialysis.	Up to 48 weeks from the date of randomization	The mean difference between the pre-dialysis and post-dialysis unsaturated iron binding capacity (UIBC) was calculated, using all post-baseline values obtained during Stage 2. Subjects could participate in Stage 2 for up to 48 weeks, provided that they did not complete Stage 2 early due to a protocol-mandated change in anemia management or withdraw from the study entirely for other reasons.
Red Blood Cell or Whole Blood Transfusion: Number of Units Transfused	up to 48 weeks from the date of randomization	The total number of units of red blood cells or whole blood that were received by patients while in the randomized treatment stage (Stage 2). This number is the total number of units received across all randomized patients in each treatment group (it is not the average number of units received per patient). Patients remained in Stage 2 until they met protocol-defined criteria for Stage 2 completion or until they had participated in Stage 2 for 48 weeks (whichever came sooner). If a patient was transfused, they were withdrawn from Stage 2.
Change From Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT)	Up to 48 weeks from the date of randomization	The Mean Change from Stage 2 Baseline to End-of-Treatment (EoT) in Pre-Dialysis Transferrin Saturation (TSAT) will be quantified.
Percentage of Change From Baseline to End-of-Treatment (EoT) for: Reticulocyte Hemoglobin Content (CHr), Ferritin, and Pre-Dialysis Serum Iron Panel	Up to 48 weeks from the date of randomization	A comparison of the lab values at the end-of-treatment (EoT) to baseline was performed, and the percentage of change from baseline was calculated for the following lab parameters: reticulocyte hemoglobin content (CHr), Ferritin, pre-dialysis unbound iron-binding capacity (UIBC), pre-dialysis serum iron, pre-dialysis transferrin, pre-dialysis total iron-binding capacity TIBC), and transferrin saturation (TSAT).
Variability of Hemoglobin Concentration: Residual Standard Deviation	Hgb measured weekly; up to 48 weeks from the date of randomization	The mean residual standard deviation of hemoglobin concentration value changes, as measured weekly from baseline until the end of participation in Stage 2.