Clinical trial NCT01503021: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: End Stage Renal Disease
Chronic Kidney Disease
Keywords: Soluble ferric pyrophosphate
Chronic kidney disease
Chronic hemodialysis
Ferric pyrophosphate citrate
Lead sponsor: Rockwell Medical Technologies, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-02
Enrollment: 718
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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/exclusion criteria are met).
4. 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:

1. 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.
2. Non-tunneled vascular catheter for dialysis.
3. Scheduled for kidney transplant within 12 weeks after entry into extension phase.
4. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to dosing.
5. Pregnancy or intention to become pregnant during the study.

Primary outcomes:
measure: Incidence of Treatment-emergent Adverse Events
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
measure: Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
measure: Incidence of Related Suspected Hypersensitivity Reactions
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Secondary outcomes:
measure: Incidence of Composite Cardiovascular Events
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
measure: Incidence of Hemodialysis Vascular Access Thrombotic Events
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
measure: Incidence of Other Thrombotic Events
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
measure: Incidence of Systemic/Serious Infections
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
measure: Incidence of Serious Adverse Events
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Other outcomes:
measure: Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2
timeFrame: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study
measure: Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5
timeFrame: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study
measure: Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2
timeFrame: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study
measure: Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5
timeFrame: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study
measure: Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2
timeFrame: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study
measure: Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5
timeFrame: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study
measure: Ferritin
timeFrame: Baseline, up to 53 weeks for Extension Study
measure: Serum Iron
timeFrame: Baseline, up to 53 weeks for Extension Study
measure: Transferrin Saturation
timeFrame: Baseline, up to 53 weeks for Extension Study
measure: Incidence of Patients Meeting Hy's Law Criteria
timeFrame: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
Locations:
city: Mobile
country: United States
state: Alabama
city: Northridge
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Westminster
country: United States
state: Colorado
city: Lauderhill
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Columbus
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Baton Rouge
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Camp Springs
country: United States
state: Maryland
city: Gulfport
country: United States
state: Mississippi
city: McComb
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: St. Peters
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Reno
country: United States
state: Nevada
city: Rocky Mount
country: United States
state: North Carolina
city: Dayton
country: United States
state: Ohio
city: Columbia
country: United States
state: South Carolina
city: Houston
country: United States
facility: Research Across America
state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: Mission
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Courtice
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Regina
country: Canada
state: Saskatchewan
Study officials:
affiliation: Rockwell Medical, Inc
name: Ray Pratt, MD
role: STUDY_DIRECTOR
References: