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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01503021

Enrollment

718

Registered

2012-01-02

Start date

2011-11-30

Completion date

2014-01-31

Last updated

2016-10-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Disease, End Stage Renal Disease

Keywords

Soluble ferric pyrophosphate, Chronic kidney disease, Chronic hemodialysis, Ferric pyrophosphate citrate

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.

Interventions

DRUGSFP

Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate

OTHERPlacebo

Dialysis with standard liquid bicarbonate concentrate without iron

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Parent Study, Double Blinded, Crossover: Key Inclusion Criteria: 1. Adult ≥ 18 years of age. 2. Has chronic kidney disease (CKD) receiving maintenance hemodialysis (HD) (CKD-HD subjects) and regularly undergoing 2 or more dialysis sessions per week. 3. Stable pre-dialysis Hgb ≥ 9.0 to ≤ 12.5 g/dL. 4. Stable pre-dialysis TSAT ≥ 15% to ≤ 45%. 5. Stable pre-dialysis ferritin ≥ 100 to ≤ 1200 µg/L (1200 ng/mL). Key

Exclusion criteria

1. Any previous exposure to SFP. 2. 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. 3. Non-tunneled vascular catheter for dialysis. 4. Scheduled for kidney transplant within the next 8 weeks. 5. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to screening, or during screening period prior to randomization. 6. Hospitalization within 1 month prior to screening (except for vascular access surgery). Extension Study, Open Label, Single Active Arm: Key Inclusion Criteria: 1. Participated in Parent Study RMTI-SFP-6 and completed the follow-up/early term visit. 2. Hemoglobin ≤12.0 g/dL at screening. 3. TSAT ≤45% at screening. (Excursion of TSAT by ≤10% outside this range permitted only if all other inclusion/

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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.
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 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.

Other

Measure	Time frame	Description
Transferrin Saturation	Baseline, up to 53 weeks for Extension Study	The baseline and end of treatment predialysis transferrin saturation were evaluated for the 52-week extension study to confirm clearance of iron derived from soluble ferric pyrophosphate.
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2	Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study	Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.
Incidence of Patients Meeting Hy's Law Criteria	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	The peak alanine aminotransferase and the peak total bilirubin levels were evaluated per patient. Laboratory values 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. Patients with alanine aminotransferase more than three times the upper limit of normal and also total bilirubin more than two times the upper limit of normal are counted.
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5	Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study	Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2	Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study	Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5	Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study	Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2	Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study	Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5	Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study	Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.
Ferritin	Baseline, up to 53 weeks for Extension Study	The baseline and end of treatment predialysis ferritin levels were evaluated for the 52-week extension study to determine whether soluble ferric pyrophosphate increases iron stores.
Serum Iron	Baseline, up to 53 weeks for Extension Study	The baseline and end of treatment predialysis serum iron levels were evaluated for the 52-week extension study to determine the effect of soluble ferric pyrophosphate on serum iron.

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
SFP/Placebo Soluble ferric pyrophosphate (SFP) 2 µM (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	351
Placebo/SFP Standard liquid bicarbonate concentrate without SFP x 2 weeks, then 1 week washout, then soluble ferric pyrophosphate (SFP) 2 µM (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks.	352
Total	703

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	7	6
Overall Study	Death	0	2
Overall Study	Lost to Follow-up	2	0
Overall Study	Moved, received transplant, etc.	5	7
Overall Study	Physician Decision	3	0
Overall Study	Protocol Violation	1	3
Overall Study	Withdrawal by Subject	9	8

Baseline characteristics

Characteristic	Placebo/SFP	Total	SFP/Placebo
Age, Continuous	59.5 years STANDARD_DEVIATION 13.3	59.7 years STANDARD_DEVIATION 13.23	59.9 years STANDARD_DEVIATION 13.18
Ethnicity (NIH/OMB) Hispanic or Latino	106 Participants	196 Participants	90 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	246 Participants	507 Participants	261 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	5 Participants	5 Participants
Race (NIH/OMB) Asian	8 Participants	14 Participants	6 Participants
Race (NIH/OMB) Black or African American	145 Participants	299 Participants	154 Participants
Race (NIH/OMB) More than one race	5 Participants	6 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	194 Participants	379 Participants	185 Participants
Sex: Female, Male Female	141 Participants	278 Participants	137 Participants
Sex: Female, Male Male	211 Participants	425 Participants	214 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	123 / 693	131 / 687	253 / 309
serious Total, serious adverse events	30 / 693	35 / 687	144 / 309