Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis

Study Overview
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Brief Summary
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The purpose of the parent study is to assess the short-term safety and tolerability of soluble ferric pyrophosphate (SFP) in dialysate administered to a large number of representative adult chronic kidney disease patients on hemodialysis (CKD-HD). The purpose of the extension study is to assess the long-term safety and tolerability of SFP.

Detailed Description
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Parent Study: randomized, double-blinded, crossover, up to 6 weeks, 700 patients. Patients were randomized to receive SFP 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate or placebo (standard liquid bicarbonate concentrate) x 2 weeks, then a 1 week washout, then crossed over to the alternate treatment x 2 weeks. Extension Study: open-label, single active arm, uncontrolled study, up to 53 weeks, 300 patients. Following completion of the RMTI-SFP-6 parent study, patients could enter the extension study, where they received SFP 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate for up to 52 weeks.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Crossover, Multicenter Phase III Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in Chronic Kidney Disease Patients Receiving Chronic Hemodialysis

Conditions
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End Stage Renal Disease, Chronic Kidney Disease

Intervention / Treatment
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* Drug: SFP
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Parent Study, Double Blinded, Crossover: Key Inclusion Criteria: Adult ≥ 18 years of age. Has chronic kidney disease (CKD) receiving maintenance hemodialysis (HD) (CKD-HD subjects) and regularly undergoing 2 or more dialysis sessions per week. Stable pre-dialysis Hgb ≥ 9.0 to ≤ 12.5 g/dL. Stable pre-dialysis TSAT ≥ 15% to ≤ 45%. Stable pre-dialysis ferritin ≥ 100 to ≤ 1200 µg/L (1200 ng/mL). Key Exclusion Criteria: Any previous exposure to SFP. Therapy with intravenous, intramuscular or oral iron at any time between the first/screening visit and the randomization visit, or anticipated requirement for iron supplementation during the study period. Non-tunneled vascular catheter for dialysis. Scheduled for kidney transplant within the next 8 weeks. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to screening, or during screening period prior to randomization. Hospitalization within 1 month prior to screening (except for vascular access surgery). Extension Study, Open Label, Single Active Arm: Key Inclusion Criteria: Participated in Parent Study RMTI-SFP-6 and completed the follow-up/early term visit. Hemoglobin ≤12.0 g/dL at screening. TSAT ≤45% at screening. (Excursion of TSAT by ≤10% outside this range permitted only if all other inclusion/exclusion criteria are met). Serum ferritin ≤1000 µg/L at screening. (Excursion of ferritin by ≤10% outside this range permitted only if all other inclusion/exclusion criteria are met). Key Exclusion Criteria: Had a serious adverse event attributable (i.e., probably, possibly, or definitely related) to study drug or had an adverse event attributable to study drug that necessitated premature withdrawal from the double-blind, placebo-controlled crossover phase of the parent study RMTI-SFP-6. Non-tunneled vascular catheter for dialysis. Scheduled for kidney transplant within 12 weeks after entry into extension phase. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to dosing. Pregnancy or intention to become pregnant during the study.

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: SFP/Placebo<br>Soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks, then 1 week washout, then standard liquid bicarbonate concentrate without SFP x 2 weeks | Drug: SFP<br>* Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate<br>* Other names: Soluble ferric pyrophosphate;Other: Placebo<br>* Dialysis with standard liquid bicarbonate concentrate without iron<br>* Other names: Standard liquid bicarbonate concentrate;|
| Other: Placebo/SFP<br>Standard liquid bicarbonate concentrate without SFP x 2 weeks, then 1 week washout, then soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks. | Drug: SFP<br>* Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate<br>* Other names: Soluble ferric pyrophosphate;Other: Placebo<br>* Dialysis with standard liquid bicarbonate concentrate without iron<br>* Other names: Standard liquid bicarbonate concentrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent Adverse Events | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 
| Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met the protocol criteria for intradialytic hypotension. Intradialytic hypotension events were only to have been reported as adverse events if they exceeded the individual subject's baseline pattern of intradialytic hypotension. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 
| Incidence of Related Suspected Hypersensitivity Reactions | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met protocol criteria for suspected hypersensitivity reactions. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Composite Cardiovascular Events | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for composite cardiovascular events were pre-specified in the statistical analysis plan for the study. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 
| Incidence of Hemodialysis Vascular Access Thrombotic Events | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for hemodialysis vascular access thrombotic events were pre-specified in the statistical analysis plan for the study. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 
| Incidence of Other Thrombotic Events | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for other thrombotic events were pre-specified in the statistical analysis plan for the study. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 
| Incidence of Systemic/Serious Infections | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse events of systemic/serious infections were defined in the statistical analysis plan for the study to include infections for which the subject was administered at least 3 doses of an IV antibiotic, and infections for which the subject was hospitalized. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 
| Incidence of Serious Adverse Events | Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met seriousness criteria. | Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease, Chronic hemodialysis, Ferric pyrophosphate citrate, Soluble ferric pyrophosphate