Anemia of Chronic Kidney Disease
Conditions
Keywords
ferric citrate, Chronic kidney disease, Anemia
Brief summary
a 24-week phase 3, multi-center clinical trial, comprised of a 16-week, randomized, double-blind, placebo-controlled period (Randomized Period), followed by an 8-week open-label safety extension period, where all subjects receive KRX-0502 (ferric citrate) (Extension Period).
Detailed description
a 24-week phase 3, multi-center clinical trial, comprised of a 16-week, randomized, double-blind, placebo-controlled period (Randomized Period), followed by an 8-week open-label safety extension period, where all subjects receive KRX-0502 (ferric citrate) (Extension Period). The study will consist of 14 clinic visits over a period of 24 weeks. There will be a screening period of up to 14 days; Approximately 230 subjects will be randomized into the Randomized Period in a 1:1 ratio to receive either KRX-0502 or matching placebo, at baseline
Interventions
DRUGferric citrate
1 g ferric citrate containing approximately 210 mg of ferric iron
DRUGPlacebo
Matching placebo
Sponsors
Keryx Biopharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and non-lactating women with negative serum pregnancy test (for women of child-bearing potential) at Screening 2. Age ≥18 years 3. CKD with Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min at Screening using the 4-variable Modification of Diet in Renal Disease (MDRD) equation (with a limit of up to 20% of the target randomization of 230 subjects with eGFR \<15 mL/min) 4. Patients who were intolerant of or have had an inadequate therapeutic response to oral iron supplements (in the opinion of the investigator) 5. Hgb ≥ 9.0 g/dL and ≤11.5 g/dL at Screening 6. Serum ferritin ≤200 ng/mL and Transferrin Saturation (TSAT) ≤25% at Screening 7. Serum Intact Parathyroid Hormone (iPTH) ≤600 pg/mL at Screening 8. Must consume a minimum of 2 meals per day 9. Willing and able to give written informed consent
Exclusion criteria
1. Serum phosphate \<3.5 mg/dL at Screening 2. Liver enzymes (ALT/AST) \>X3 times upper limit of normal at Screening 3. Symptomatic gastrointestinal bleeding or inflammatory bowel disease within 12 weeks prior to Screening 4. Evidence of acute kidney injury or requirement for dialysis within 12 weeks prior to Screening 5. Scheduled kidney transplant or initiation of dialysis planned within 24 weeks of Screening 6. IV iron administered within 4 weeks prior to Screening 7. Erythropoiesis-stimulating agent (ESA) administered within 4 weeks prior to Screening 8. Blood transfusion within 4 weeks prior to Screening 9. Receipt of any investigational drug within 4 weeks prior to Screening 10. Cause of anemia other than iron deficiency or chronic kidney disease 11. Malignancy (except non-melanoma skin cancer or disease-free for ≥2 years after curative therapy) 12. History of hemochromatosis 13. Active drug or alcohol dependence or abuse (excluding tobacco use or medicinal marijuana) within the 12 months prior to Screening or evidence of such abuse (in the opinion of the PI) 14. Subjects with known allergic reaction to previous oral iron therapy 15. Previous intolerance to oral ferric citrate 16. Psychiatric disorder that interferes with the subject's ability to comply with the study protocol 17. Planned surgery or hospitalization (anticipated to last \>72 hours) during the randomized period of the trial other than dialysis access related surgery. 18. Any other medical condition that, in the opinion of the PI, renders the subject unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the subject 19. Inability to cooperate with study personnel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving an Increase in Hemoglobin of ≥1.0 g/dL at Any Time Point Between Baseline and the End of the 16-week Randomized Period | Week 16 | Efficacy analyses were performed for the Intention-to-treat (ITT) population, the population consisted of all subjects who were randomized, had a baseline laboratory value, took at least 1 dose of study drug, and had at least 1 post-baseline laboratory assessment during the randomized period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Serum Phosphate at the End of 16 Weeks Minus Baseline | Baseline and week 16 | The difference of serum phosphate at 16 weeks compared to the serum phosphate value at the time of study entry. |
| Mean Change in Ferritin at the End of 16 Weeks Minus Baseline | Baseline and week 16 | The difference of ferritin at 16 weeks compared to the ferritin value at the time of study entry. |
| Percentage of Subjects Experiencing a Sustained Treatment Effect on Hemoglobin (Hgb) | Week 16 | Proportion of subjects that continued to maintain an increase in Hgb over a 4 week period, provided they had an increase of at least 1.0 g/dL during that 4-week period |
| Mean Change in Hemoglobin (Hgb) at the End of 16 Weeks Minus Baseline | Baseline and week 16 | The difference of Hgb at 16 weeks compared to the Hgb value at the time of study entry. |
| Mean Change in Transferrin Saturation (TSAT) at the End of 16 Weeks Minus Baseline | Baseline and week 16 | The difference of TSAT at 16 weeks compared to the TSAT value at the time of study entry was averaged. |
Countries
United States
Participant flow
Pre-assignment details
1 randomized subject was excluded because they did not receive study drug and were excluded from the safety population.
Participants by arm
| Arm | Count |
|---|---|
| KRX-0502 (Ferric Citrate) 1 g of KRX-0502 (ferric citrate) containing approximately 210 mg of ferric iron
ferric citrate: 1 g ferric citrate containing approximately 210 mg of ferric iron | 117 |
| Placebo Matching Placebo
Placebo: Matching placebo | 116 |
| Total | 233 |
Baseline characteristics
| Characteristic | KRX-0502 (Ferric Citrate) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 69 Participants | 68 Participants | 137 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 48 Participants | 96 Participants |
| Age, Continuous | 65.6 years STANDARD_DEVIATION 11.15 | 65.2 years STANDARD_DEVIATION 13.08 | 65.4 years STANDARD_DEVIATION 12.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 24 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 92 Participants | 180 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 31 Participants | 69 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 78 Participants | 82 Participants | 160 Participants |
| Sex: Female, Male Female | 76 Participants | 71 Participants | 147 Participants |
| Sex: Female, Male Male | 41 Participants | 45 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 117 | 0 / 116 |
| other Total, other adverse events | 61 / 117 | 41 / 116 |
| serious Total, serious adverse events | 14 / 117 | 13 / 116 |
Outcome results
Primary
Percentage of Subjects Achieving an Increase in Hemoglobin of ≥1.0 g/dL at Any Time Point Between Baseline and the End of the 16-week Randomized Period
Efficacy analyses were performed for the Intention-to-treat (ITT) population, the population consisted of all subjects who were randomized, had a baseline laboratory value, took at least 1 dose of study drug, and had at least 1 post-baseline laboratory assessment during the randomized period.
Time frame: Week 16
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KRX-0502 (Ferric Citrate) | Percentage of Subjects Achieving an Increase in Hemoglobin of ≥1.0 g/dL at Any Time Point Between Baseline and the End of the 16-week Randomized Period | 61 Participants |
| Placebo | Percentage of Subjects Achieving an Increase in Hemoglobin of ≥1.0 g/dL at Any Time Point Between Baseline and the End of the 16-week Randomized Period | 22 Participants |
Secondary
Mean Change in Ferritin at the End of 16 Weeks Minus Baseline
The difference of ferritin at 16 weeks compared to the ferritin value at the time of study entry.
Time frame: Baseline and week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 (Ferric Citrate) | Mean Change in Ferritin at the End of 16 Weeks Minus Baseline | 68.1 ng/mL | Standard Error 3.99 |
| Placebo | Mean Change in Ferritin at the End of 16 Weeks Minus Baseline | -6.1 ng/mL | Standard Error 4.1 |
Secondary
Mean Change in Hemoglobin (Hgb) at the End of 16 Weeks Minus Baseline
The difference of Hgb at 16 weeks compared to the Hgb value at the time of study entry.
Time frame: Baseline and week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 (Ferric Citrate) | Mean Change in Hemoglobin (Hgb) at the End of 16 Weeks Minus Baseline | 0.39 g/dL | Standard Error 0.054 |
| Placebo | Mean Change in Hemoglobin (Hgb) at the End of 16 Weeks Minus Baseline | -0.14 g/dL | Standard Error 0.056 |
Secondary
Mean Change in Serum Phosphate at the End of 16 Weeks Minus Baseline
The difference of serum phosphate at 16 weeks compared to the serum phosphate value at the time of study entry.
Time frame: Baseline and week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 (Ferric Citrate) | Mean Change in Serum Phosphate at the End of 16 Weeks Minus Baseline | -0.28 mg/dL | Standard Error 0.036 |
| Placebo | Mean Change in Serum Phosphate at the End of 16 Weeks Minus Baseline | -0.14 mg/dL | Standard Error 0.037 |
Secondary
Mean Change in Transferrin Saturation (TSAT) at the End of 16 Weeks Minus Baseline
The difference of TSAT at 16 weeks compared to the TSAT value at the time of study entry was averaged.
Time frame: Baseline and week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 (Ferric Citrate) | Mean Change in Transferrin Saturation (TSAT) at the End of 16 Weeks Minus Baseline | 10.9 % saturation | Standard Error 0.65 |
| Placebo | Mean Change in Transferrin Saturation (TSAT) at the End of 16 Weeks Minus Baseline | -1.3 % saturation | Standard Error 0.67 |
Secondary
Percentage of Subjects Experiencing a Sustained Treatment Effect on Hemoglobin (Hgb)
Proportion of subjects that continued to maintain an increase in Hgb over a 4 week period, provided they had an increase of at least 1.0 g/dL during that 4-week period
Time frame: Week 16
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KRX-0502 (Ferric Citrate) | Percentage of Subjects Experiencing a Sustained Treatment Effect on Hemoglobin (Hgb) | 57 Participants |
| Placebo | Percentage of Subjects Experiencing a Sustained Treatment Effect on Hemoglobin (Hgb) | 17 Participants |