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

Phase 3

Completed

Conditions: End Stage Renal Disease
Chronic Kidney Disease

Interventions: Drug: SFP
Other: Placebo

Registration Number: NCT01503021

Lead Sponsor: Rockwell Medical Technologies, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 718

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
SFP/Placebo	SFP	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
SFP/Placebo	Placebo	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
Placebo/SFP	Placebo	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.
Placebo/SFP	SFP	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-emergent Adverse Events	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.
Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.
Incidence of Related Suspected Hypersensitivity Reactions	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of Hemodialysis Vascular Access Thrombotic Events	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.
Incidence of Composite Cardiovascular Events	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.
Incidence of Other Thrombotic Events	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.
Incidence of Systemic/Serious Infections	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.
Incidence of Serious Adverse Events	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	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.