Anemia, Iron Deficiency, Cardiovascular, Disease Progression, Hyperphosphatemia, Iron, Renal Anemia, Renal Insufficiency, Chronic
Conditions
Keywords
ferric citrate
Brief summary
A 9-month randomized, double-blind, placebo-controlled study to compare the effect of fixed dose ferric citrate versus placebo in patients with advanced chronic kidney disease (eGFR ≤20 ml/min/1.73m2) on the composite endpoint of time to initiation of maintenance dialysis or all-cause mortality.
Detailed description
This multicenter, randomized, double-blind, placebo-controlled clinical trial is being conducted to determine the effect of ferric citrate on the time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality in patients with non-dialysis dependent, advanced CKD. Up to 400 subjects will be randomized in 1:1 ratio to receive either ferric citrate or matching placebo. All subjects will initiate dosing at 2 tablets per meal or snacks, up to 3 times per day (maximum of 6 tablets per day). The dose of ferric citrate/placebo will only be adjusted based on safety and/or tolerability. Given the double-blind design of this trial, investigators will be instructed to not prescribe commercial Auryxia to either study arm. Study visits during the treatment period are to be conducted as part of routine scheduled clinical encounters. Standard of care local laboratory results will be collected however no study specific laboratory tests other than a pregnancy test in women of child-bearing potential will be required.
Interventions
DRUGFerric Citrate 1 GM Oral Tablet [AURYXIA]
All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.
DRUGPlacebo
All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.
Sponsors
Akebia Therapeutics
USRC Kidney Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, placebo controlled, double-blind, parallel assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients greater or equal to 18 years old. 2. Diagnosis of NDD advanced CKD, regardless of etiology. Advanced CKD is defined as at least one local laboratory determined estimated glomerular filtration rate (eGFR) ≤20 ml/min/1.73m2 (calculated per any commonly used method or equation for estimating eGFR) within 90 days of Day 1. 3. Most recent transferrin saturation (TSAT) less than or equal to 45% within 45 days of Day 1. 4. Most recent serum phosphate is greater or equal to 3.0 mg per dL within 45 days of Day 1. 5. Most recent ferritin is less than or equal to 500 ng per mL within 45 days of Day 1. 6. Women of child-bearing potential must have a negative serum or urine pregnancy test within 28 days prior to Day 1. 7. Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.
Exclusion criteria
1. Patients who, in the opinion of the Investigator, have acute kidney injury rather than CKD. 2. Patients with planned/imminent maintenance dialysis, or that are anticipated to begin maintenance dialysis within 8 weeks from Screening, in the opinion of the Investigator. 3. A known allergy or intolerance to ferric citrate or any of its constituents. 4. Hypersensitivity reaction to previous oral iron therapy. 5. History of hemochromatosis or iron overload syndrome (e.g., hereditary sideroblastic anemia, thalassemia, polycythemia vera). 6. Active malignancy requiring current treatment except for non-melanoma skin cancer regardless of treatment. 7. Active drug or alcohol dependence or abuse (excluding tobacco use or use of medical or recreational marijuana) within the 12 months prior to Screening or evidence of such abuse, in the opinion of the Investigator. 8. Limited life expectancy (less than 6 months) in the opinion of the Investigator. 9. Females who are known to be pregnant or are breast-feeding during Screening or are planning to become pregnant and breastfeeding during the study period. 10. Evidence of a clinically active infection requiring antibiotics at Randomization. 11. Unable to comply with study requirements or in the opinion of the Investigator, not clinically stable to participate in the study. 12. Use of an investigational medication or participation in an investigational study within 30 days prior to Day 1. 13. Patients with a scheduled date for receipt of living donor kidney transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality | 9 months | Number of participants achieving a composite endpoint of initiation of maintenance dialysis or all-cause mortality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization Events Reported as a Serious Adverse Event (SAE) (Excluding Disease-related Hospitalization [e.g., Dialysis Access Placement, Dialysis Initiation, Kidney Transplant] and Elective Procedures) | 9 months | Number of hospitalization events reported as a serious adverse event (SAE) (excluding disease-related hospitalization \[e.g., dialysis access placement, dialysis initiation, kidney transplant\] and elective procedures) |
| Component of Primary - Initiation of Maintenance Dialysis | 9 months | Component of Primary - Number of participants initiating maintenance dialysis |
| Component of Primary - All-Cause Mortality | 9 months | Component of Primary - Number of patients reaching endpoint of all-cause mortality. |
Countries
United States
Participant flow
Recruitment details
This was a randomized, double-blind, placebo-controlled clinical trial to assess the effect of ferric citrate on the time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality compared with placebo in adults with advanced chronic kidney disease.
Pre-assignment details
A total of 289 patients were randomized 1:1 to receive ferric citrate (n=144) or placebo (n=145).
Participants by arm
| Arm | Count |
|---|---|
| Ferric Citrate Supplied as tablets for oral administration containing 1 gram ferric citrate (210 milligrams of ferric iron). Administered orally with meals or snacks. | 138 |
| Placebo Tablets, matching in color and size to ferric citrate. | 136 |
| Total | 274 |
Baseline characteristics
| Characteristic | Ferric Citrate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 13.1 | 68.2 years STANDARD_DEVIATION 12.9 | 67 years STANDARD_DEVIATION 13 |
| Comorbid conditions at baseline Atherosclerotic cardiovascular disease | 41 Participants | 55 Participants | 96 Participants |
| Comorbid conditions at baseline Congestive heart failure | 20 Participants | 30 Participants | 50 Participants |
| Comorbid conditions at baseline Diabetes | 92 Participants | 86 Participants | 178 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 21 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants | 18 Participants | 38 Participants |
| Race (NIH/OMB) White | 94 Participants | 97 Participants | 191 Participants |
| Sex: Female, Male Female | 79 Participants | 71 Participants | 150 Participants |
| Sex: Female, Male Male | 59 Participants | 65 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 138 | 6 / 136 |
| other Total, other adverse events | 0 / 138 | 0 / 136 |
| serious Total, serious adverse events | 33 / 138 | 43 / 136 |
Outcome results
Primary
Number of Participants Achieving a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality
Number of participants achieving a composite endpoint of initiation of maintenance dialysis or all-cause mortality
Time frame: 9 months
Population: Full analysis set which consists of randomized patients who received one or more doses of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ferric Citrate | Number of Participants Achieving a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality | 35 Participants |
| Placebo | Number of Participants Achieving a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality | 46 Participants |
p-value: 0.160295% CI: [0.46, 1.14]Regression, Cox
Secondary
Component of Primary - All-Cause Mortality
Component of Primary - Number of patients reaching endpoint of all-cause mortality.
Time frame: 9 months
Population: Full analysis set population which consists of all randomized patients who received one or more doses of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ferric Citrate | Component of Primary - All-Cause Mortality | 1 Participants |
| Placebo | Component of Primary - All-Cause Mortality | 4 Participants |
p-value: 0.17Regression, Cox
Secondary
Component of Primary - Initiation of Maintenance Dialysis
Component of Primary - Number of participants initiating maintenance dialysis
Time frame: 9 months
Population: Full analysis set population which consists of all randomized patients who received one or more doses of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ferric Citrate | Component of Primary - Initiation of Maintenance Dialysis | 24 Participants |
| Placebo | Component of Primary - Initiation of Maintenance Dialysis | 29 Participants |
p-value: 0.3Regression, Cox
Secondary
Hospitalization Events Reported as a Serious Adverse Event (SAE) (Excluding Disease-related Hospitalization [e.g., Dialysis Access Placement, Dialysis Initiation, Kidney Transplant] and Elective Procedures)
Number of hospitalization events reported as a serious adverse event (SAE) (excluding disease-related hospitalization \[e.g., dialysis access placement, dialysis initiation, kidney transplant\] and elective procedures)
Time frame: 9 months
Population: Full analysis set population which consists of all randomized patients who received one or more doses of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Citrate | Hospitalization Events Reported as a Serious Adverse Event (SAE) (Excluding Disease-related Hospitalization [e.g., Dialysis Access Placement, Dialysis Initiation, Kidney Transplant] and Elective Procedures) | 1.1 Number of hospitalizations per patient | Standard Deviation 2.4 |
| Placebo | Hospitalization Events Reported as a Serious Adverse Event (SAE) (Excluding Disease-related Hospitalization [e.g., Dialysis Access Placement, Dialysis Initiation, Kidney Transplant] and Elective Procedures) | 2.5 Number of hospitalizations per patient | Standard Deviation 9.4 |