Back to resultsSafety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis
Primary Purpose
End Stage Renal Disease, Chronic Kidney Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SFP
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for End Stage Renal Disease focused on measuring Soluble ferric pyrophosphate, Chronic kidney disease, Chronic hemodialysis, Ferric pyrophosphate citrate
Eligibility Criteria
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.
Sites / Locations
- Research Across America
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
SFP/Placebo
Placebo/SFP
Arm Description
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
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01503021
First Posted
December 29, 2011
Last Updated
September 14, 2016
Sponsor
Rockwell Medical Technologies, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01503021
Brief Title
Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rockwell Medical Technologies, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease, Chronic Kidney Disease
Keywords
Soluble ferric pyrophosphate, Chronic kidney disease, Chronic hemodialysis, Ferric pyrophosphate citrate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
718 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SFP/Placebo
Arm Type
Other
Arm Description
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
Arm Title
Placebo/SFP
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
SFP
Other Intervention Name(s)
Soluble ferric pyrophosphate
Intervention Description
Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Standard liquid bicarbonate concentrate
Intervention Description
Dialysis with standard liquid bicarbonate concentrate without iron
Primary Outcome Measure Information:
Title
Incidence of Treatment-emergent Adverse Events
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Title
Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Title
Incidence of Related Suspected Hypersensitivity Reactions
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Secondary Outcome Measure Information:
Title
Incidence of Composite Cardiovascular Events
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Title
Incidence of Hemodialysis Vascular Access Thrombotic Events
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Title
Incidence of Other Thrombotic Events
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Title
Incidence of Systemic/Serious Infections
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Title
Incidence of Serious Adverse Events
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Other Pre-specified Outcome Measures:
Title
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2
Description
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.
Time Frame
Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study
Title
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5
Description
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.
Time Frame
Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study
Title
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2
Description
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.
Time Frame
Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study
Title
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5
Description
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.
Time Frame
Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study
Title
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2
Description
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.
Time Frame
Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study
Title
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5
Description
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.
Time Frame
Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study
Title
Ferritin
Description
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.
Time Frame
Baseline, up to 53 weeks for Extension Study
Title
Serum Iron
Description
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.
Time Frame
Baseline, up to 53 weeks for Extension Study
Title
Transferrin Saturation
Description
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.
Time Frame
Baseline, up to 53 weeks for Extension Study
Title
Incidence of Patients Meeting Hy's Law Criteria
Description
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.
Time Frame
Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ray Pratt, MD
Organizational Affiliation
Rockwell Medical, Inc
Official's Role
Study Director
Facility Information:
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36688
Country
United States
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
City
Arvada
State/Province
Colorado
ZIP/Postal Code
80002
Country
United States
City
Westminster
State/Province
Colorado
ZIP/Postal Code
80031
Country
United States
City
Lauderhill
State/Province
Florida
ZIP/Postal Code
33319
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60616
Country
United States
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61603
Country
United States
City
Columbus
State/Province
Indiana
ZIP/Postal Code
47201
Country
United States
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
City
Camp Springs
State/Province
Maryland
ZIP/Postal Code
20748
Country
United States
City
Gulfport
State/Province
Mississippi
ZIP/Postal Code
39501
Country
United States
City
McComb
State/Province
Mississippi
ZIP/Postal Code
39648
Country
United States
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
City
St. Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
City
Reno
State/Province
Nevada
ZIP/Postal Code
89511
Country
United States
City
Rocky Mount
State/Province
North Carolina
ZIP/Postal Code
27804
Country
United States
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45428
Country
United States
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29209
Country
United States
Facility Name
Research Across America
City
Houston
State/Province
Texas
ZIP/Postal Code
75234
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77051
Country
United States
City
Irving
State/Province
Texas
ZIP/Postal Code
75061
Country
United States
City
Mission
State/Province
Texas
ZIP/Postal Code
78572
Country
United States
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
City
Courtice
State/Province
Ontario
ZIP/Postal Code
L1E 3C3
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
54P 0W5
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis
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