Chronic Kidney Diseases, Iron Deficiency Anemia
Conditions
Brief summary
The objectives of this study are to assess the long-term efficacy and safety of different dose regimens of KRX-0502 in the treatment of iron deficiency anemia (IDA) in adult subjects with non-dialysis dependent chronic kidney disease (CKD).
Detailed description
This is a Phase 4, 48-week, randomized, open-label, multicenter clinical study comprised of 2 periods: a 24-week Dose Titration Period, followed by a 24-week Dose Maintenance Period. The study will consist of 12 scheduled clinic visits over a period of 48 weeks and additional visits as needed.
Interventions
DRUGKRX-0502
Oral ferric citrate with meals
Sponsors
Keryx Biopharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Estimated glomerular filtration rate ≥20 mL/min and \<60 mL/min * Hgb ≥8.5 g/dL and ≤11.5 g/dL * Serum ferritin ≤500 ng/mL and transferrin saturation (TSAT) ≤25% * Serum intact parathyroid hormone ≤600 pg/mL
Exclusion criteria
* Serum phosphate \<3.0 mg/dL * Intravenous (IV) iron administered within 4 weeks prior to Screening * Erythropoiesis-stimulating agents (ESA) administered within 4 weeks prior to Screening * Blood transfusion within 4 weeks prior to Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin (Hgb) at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from a mixed model of repeated measures (MMRM), including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to the First Increase From Baseline Hgb of at Least 0.5 Grams Per Deciliter (g/dL) During the Dose Titration Period | from Randomization to Week 24 | The Kaplan-Meier estimator of the survival function of time from randomization to the first increase from Baseline Hgb of at least 0.5 g/dL for each of the two starting dose treatment groups were obtained. |
| Change From Baseline in Transferrin Saturation (TSAT) at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in TSAT at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Ferritin at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Ferritin at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Serum Phosphate at Week 24 | Baseline; up to Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Serum Phosphate at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in eGFR at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Bicarbonate at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Bicarbonate at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in Intact Parathyroid Hormone (iPTH) at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using a common slope analysis of covariance (ANCOVA) model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, and a random error term. |
| Change From Baseline in iPTH at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term. |
| Change From Baseline in Hgb at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix. |
| Change From Baseline in C-terminal FGF23 at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term. |
| Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using a common slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, and a random error term. |
| Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term. |
| Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact. |
| Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact. |
| Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 24: Activity Impairment | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact. |
| Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Activity Impairment | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Score at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Participants were asked to respond to 13 statements (as they apply to the last 7 days) that other people with the same illness said are important with one of the following: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. All individual items were summed to create a single fatigue score ranging from 0 to 52. Higher scores indicate greater fatigue. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue Scale Score at Week 48 | Baseline; Week 48 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Participants were asked to respond to 13 statements (as they apply to the last 7 days) that other people with the same illness said are important with one of the following: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. All individual items were summed to create a single fatigue score ranging from 0 to 52. Higher scores indicate greater fatigue. |
| Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period | up to Week 48 | A hospitalization is defined as admission to the hospital. |
| Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period | up to Week 48 | A hospitalization is defined as admission to the hospital. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) for Participants Who Entered the Dose Maintenance Period | up to Week 48 | Treatment-emergent adverse events are defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication. |
| Change From Baseline in C-terminal Fibroblast Growth Factor 23 (FGF23) at Week 24 | Baseline; Week 24 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KRX-0502 3 g/Day Participants were randomized to receive KRX-0502 3 grams per day (g/day), administered as 1 tablet 3 times daily (TID) (total of 3 tablets/day) with meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the hemoglobin (Hgb) increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12. | 104 |
| KRX-0502 4 g/Day Participants were randomized to receive KRX-0502 4 g/day, administered as 2 tablets twice daily (BID) with the larger of 2 daily meals, in the 24-week Dose Titration Period. Scheduled study drug dose adjustment occurred at Week 12 and was based upon the Hgb increase relative to Baseline and an Hgb threshold. Participants who completed the 24-week Dose Titration Period were eligible to enter the 24-week Dose Maintenance Period. During the Dose Maintenance Period, participants continued on the dose determined during the Dose Titration Period. The maximum dose was the dose determined at Week 12. | 101 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 24-Week Dose Maintenance Period | Adverse Event | 0 | 1 |
| 24-Week Dose Maintenance Period | Death | 0 | 1 |
| 24-Week Dose Maintenance Period | Lost to Follow-up | 1 | 1 |
| 24-Week Dose Maintenance Period | Prohibited Therapy | 1 | 0 |
| 24-Week Dose Maintenance Period | Withdrawal by Subject | 1 | 3 |
| 24-Week Dose Titration Period | Adverse Event | 7 | 8 |
| 24-Week Dose Titration Period | Captured as Other | 1 | 2 |
| 24-Week Dose Titration Period | Death | 3 | 1 |
| 24-Week Dose Titration Period | Investigator Judgement | 1 | 1 |
| 24-Week Dose Titration Period | Lost to Follow-up | 0 | 2 |
| 24-Week Dose Titration Period | Prohibited Therapy | 1 | 1 |
| 24-Week Dose Titration Period | Protocol Violation | 0 | 2 |
| 24-Week Dose Titration Period | Start Chronic Dialysis/Kidney Transplant | 0 | 1 |
| 24-Week Dose Titration Period | Study Drug Non-Compliance | 3 | 2 |
| 24-Week Dose Titration Period | Withdrawal by Subject | 8 | 7 |
Baseline characteristics
| Characteristic | KRX-0502 3 g/Day | KRX-0502 4 g/Day | Total |
|---|---|---|---|
| Age, Continous: Dose Maintenance Period | 67.6 years STANDARD_DEVIATION 11.57 | 69.6 years STANDARD_DEVIATION 8.94 | 68.6 years STANDARD_DEVIATION 10.38 |
| Age, Continuous | 68.3 years STANDARD_DEVIATION 11.22 | 69.9 years STANDARD_DEVIATION 9.81 | 69.1 years STANDARD_DEVIATION 10.55 |
| Hemoglobin | 10.40 grams per deciliter (g/dL) STANDARD_DEVIATION 0.749 | 10.51 grams per deciliter (g/dL) STANDARD_DEVIATION 0.739 | 10.45 grams per deciliter (g/dL) STANDARD_DEVIATION 0.744 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 40 Participants | 72 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 | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 68 Participants | 57 Participants | 125 Participants |
| Race (NIH/OMB): Dose Maintenance Period American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB): Dose Maintenance Period Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB): Dose Maintenance Period Black or African American | 26 Participants | 29 Participants | 55 Participants |
| Race (NIH/OMB): Dose Maintenance Period Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB): Dose Maintenance Period Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB): Dose Maintenance Period White | 48 Participants | 40 Participants | 88 Participants |
| Sex: Female, Male Female | 67 Participants | 69 Participants | 136 Participants |
| Sex: Female, Male Male | 37 Participants | 32 Participants | 69 Participants |
| Sex: Female, Male: Dose Maintenance Period Female | 46 Participants | 48 Participants | 94 Participants |
| Sex: Female, Male: Dose Maintenance Period Male | 30 Participants | 24 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 104 | 2 / 101 |
| other Total, other adverse events | 58 / 104 | 59 / 101 |
| serious Total, serious adverse events | 26 / 104 | 25 / 101 |
Outcome results
Primary
Change From Baseline in Hemoglobin (Hgb) at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from a mixed model of repeated measures (MMRM), including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set: participants in the Full Analysis Set (FAS) (randomized par. who took \>=1 dose of study medication and had \>=1 post-randomization efficacy measurement) who met the study eligibility requirements and had no major protocol deviations that affected the validity of the efficacy measurements. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Hemoglobin (Hgb) at Week 24 | 0.73 grams per deciliter (g/dL) | Standard Error 0.101 |
| KRX-0502 4 g/Day | Change From Baseline in Hemoglobin (Hgb) at Week 24 | 0.70 grams per deciliter (g/dL) | Standard Error 0.104 |
Secondary
Change From Baseline in Bicarbonate at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Bicarbonate at Week 24 | -0.15 milliquivalent (mEq)/Liter (L) | Standard Error 0.296 |
| KRX-0502 4 g/Day | Change From Baseline in Bicarbonate at Week 24 | -0.05 milliquivalent (mEq)/Liter (L) | Standard Error 0.312 |
Secondary
Change From Baseline in Bicarbonate at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Bicarbonate at Week 48 | 0.03 mEq/L | Standard Error 0.328 |
| KRX-0502 4 g/Day | Change From Baseline in Bicarbonate at Week 48 | -0.51 mEq/L | Standard Error 0.345 |
Secondary
Change From Baseline in C-terminal FGF23 at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants who completed their Week 48 Visit were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in C-terminal FGF23 at Week 48 | -85.70 RU/mL | Standard Error 23.029 |
| KRX-0502 4 g/Day | Change From Baseline in C-terminal FGF23 at Week 48 | -80.34 RU/mL | Standard Error 24.37 |
Secondary
Change From Baseline in C-terminal Fibroblast Growth Factor 23 (FGF23) at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in C-terminal Fibroblast Growth Factor 23 (FGF23) at Week 24 | -94.78 relative units (RU)/mL | Standard Error 26.393 |
| KRX-0502 4 g/Day | Change From Baseline in C-terminal Fibroblast Growth Factor 23 (FGF23) at Week 24 | -63.22 relative units (RU)/mL | Standard Error 26.392 |
Secondary
Change From Baseline in eGFR at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in eGFR at Week 48 | -1.85 ml/minute/1.73 m^3 | Standard Error 0.977 |
| KRX-0502 4 g/Day | Change From Baseline in eGFR at Week 48 | -2.20 ml/minute/1.73 m^3 | Standard Error 1.035 |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | -1.08 ml/minute/1.73 meters cubed (m^3) | Standard Error 0.836 |
| KRX-0502 4 g/Day | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24 | -1.53 ml/minute/1.73 meters cubed (m^3) | Standard Error 0.0882 |
Secondary
Change From Baseline in Ferritin at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Ferritin at Week 24 | 136.63 nanograms per millilier (ng/mL) | Standard Error 13.315 |
| KRX-0502 4 g/Day | Change From Baseline in Ferritin at Week 24 | 155.28 nanograms per millilier (ng/mL) | Standard Error 14.037 |
Secondary
Change From Baseline in Ferritin at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Ferritin at Week 48 | 251.44 ng/mL | Standard Error 29.417 |
| KRX-0502 4 g/Day | Change From Baseline in Ferritin at Week 48 | 343.27 ng/mL | Standard Error 31.148 |
Secondary
Change From Baseline in Hgb at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Hgb at Week 48 | 0.61 g/dL | Standard Error 0.114 |
| KRX-0502 4 g/Day | Change From Baseline in Hgb at Week 48 | 0.58 g/dL | Standard Error 0.119 |
Secondary
Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using a common slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, and a random error term.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 24 | -0.23 pg/mL | Standard Error 8.106 |
| KRX-0502 4 g/Day | Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 24 | -2.01 pg/mL | Standard Error 8.286 |
Secondary
Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants who completed their Week 48 Visit are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 48 | 18.52 pg/mL | Standard Error 14.741 |
| KRX-0502 4 g/Day | Change From Baseline in Intact Fibroblast Growth Factor 23 at Week 48 | 10.15 pg/mL | Standard Error 16.086 |
Secondary
Change From Baseline in Intact Parathyroid Hormone (iPTH) at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using a common slope analysis of covariance (ANCOVA) model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, and a random error term.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Intact Parathyroid Hormone (iPTH) at Week 24 | 1.64 picograms per milliliter (pg/mL) | Standard Error 4.547 |
| KRX-0502 4 g/Day | Change From Baseline in Intact Parathyroid Hormone (iPTH) at Week 24 | 0.39 picograms per milliliter (pg/mL) | Standard Error 4.647 |
Secondary
Change From Baseline in iPTH at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates obtained using an uncommon slope ANCOVA model which includes the Baseline laboratory parameter as a covariate, randomized treatment group, randomized treatment group by Baseline interaction, and a random error term.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants who completed their Week 48 Visit were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in iPTH at Week 48 | -1.49 pg/mL | Standard Error 5.385 |
| KRX-0502 4 g/Day | Change From Baseline in iPTH at Week 48 | 5.74 pg/mL | Standard Error 5.824 |
Secondary
Change From Baseline in Serum Phosphate at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; up to Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Serum Phosphate at Week 24 | -0.19 milligrams per deciliter (mg/dL) | Standard Error 0.065 |
| KRX-0502 4 g/Day | Change From Baseline in Serum Phosphate at Week 24 | -0.25 milligrams per deciliter (mg/dL) | Standard Error 0.069 |
Secondary
Change From Baseline in Serum Phosphate at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Serum Phosphate at Week 48 | -0.07 mg/dL | Standard Error 0.075 |
| KRX-0502 4 g/Day | Change From Baseline in Serum Phosphate at Week 48 | -0.20 mg/dL | Standard Error 0.079 |
Secondary
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Score at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Participants were asked to respond to 13 statements (as they apply to the last 7 days) that other people with the same illness said are important with one of the following: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. All individual items were summed to create a single fatigue score ranging from 0 to 52. Higher scores indicate greater fatigue.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Score at Week 24 | 7.22 score on a scale | Standard Deviation 10.986 |
| KRX-0502 4 g/Day | Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Score at Week 24 | 4.35 score on a scale | Standard Deviation 10.047 |
Secondary
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue Scale Score at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Participants were asked to respond to 13 statements (as they apply to the last 7 days) that other people with the same illness said are important with one of the following: 0, not at all; 1, a little bit; 2, somewhat; 3, quite a bit; 4, very much. All individual items were summed to create a single fatigue score ranging from 0 to 52. Higher scores indicate greater fatigue.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue Scale Score at Week 48 | 7.49 score on a scale | Standard Deviation 11.817 |
| KRX-0502 4 g/Day | Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue Scale Score at Week 48 | 3.68 score on a scale | Standard Deviation 9.954 |
Secondary
Change From Baseline in Transferrin Saturation (TSAT) at Week 24
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in Transferrin Saturation (TSAT) at Week 24 | 6.30 percentage of transferrin saturation | Standard Error 1.023 |
| KRX-0502 4 g/Day | Change From Baseline in Transferrin Saturation (TSAT) at Week 24 | 6.85 percentage of transferrin saturation | Standard Error 1.073 |
Secondary
Change From Baseline in TSAT at Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Estimates are from an MMRM, including an intercept term and covariates for randomized treatment, visit, treatment by visit interaction, Baseline value, and Baseline value by visit interaction. The Kenward-Roger method was used along with an unstructured covariance matrix.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline in TSAT at Week 48 | 7.97 percentage of transferrin saturation | Standard Error 1.053 |
| KRX-0502 4 g/Day | Change From Baseline in TSAT at Week 48 | 10.63 percentage of transferrin saturation | Standard Error 1.113 |
Secondary
Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data who were currently employed (working for pay) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Percent Work Time Missed | 0.00 percentage of score | Standard Deviation 0 |
| KRX-0502 3 g/Day | Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Percent Impairment while Working | -15.00 percentage of score | Standard Deviation 25.884 |
| KRX-0502 3 g/Day | Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Percent Overall Work Impairment | -15.00 percentage of score | Standard Deviation 25.884 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Percent Work Time Missed | -3.19 percentage of score | Standard Deviation 9.222 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Percent Impairment while Working | 4.00 percentage of score | Standard Deviation 30.258 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the Work Productivity and Activity Impairment (WPAI) Questionnaire Adapted for Anemia Associated With Chronic Kidney Disease (CKD) at Week 24: Work-associated Measures | Percent Overall Work Impairment | 1.40 percentage of score | Standard Deviation 26.842 |
Secondary
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 24: Activity Impairment
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact.
Time frame: Baseline; Week 24
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 24: Activity Impairment | -18.03 percentage of score | Standard Deviation 28.753 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 24: Activity Impairment | -6.34 percentage of score | Standard Deviation 31.769 |
Secondary
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Activity Impairment
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Activity Impairment | -16.71 percentage of score | Standard Deviation 36.859 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Activity Impairment | -6.72 percentage of score | Standard Deviation 36.227 |
Secondary
Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The WPAI is a questionnaire to evaluate the effect of anemia associated with Chronic Kidney Disease on the ability to work and perform regular activities. Scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact and 100% representing complete impact.
Time frame: Baseline; Week 48
Population: Per-Protocol Analysis Set. Only participants with available data who were currently employed (working for pay) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KRX-0502 3 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Percent Work Time Missed | 0.00 percentage of score | Standard Deviation 0 |
| KRX-0502 3 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Percent Impairment while Working | -11.43 percentage of score | Standard Deviation 16.762 |
| KRX-0502 3 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Percent Overall Work Impairment | -11.43 percentage of score | Standard Deviation 16.762 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Percent Work Time Missed | -3.48 percentage of score | Standard Deviation 7.412 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Percent Impairment while Working | 7.78 percentage of score | Standard Deviation 29.486 |
| KRX-0502 4 g/Day | Change From Baseline Scores for the WPAI Questionnaire Adapted for Anemia Associated With CKD at Week 48: Work-associated Measures | Percent Overall Work Impairment | 4.71 percentage of score | Standard Deviation 24.601 |
Secondary
Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period
A hospitalization is defined as admission to the hospital.
Time frame: up to Week 48
Population: Per-Protocol Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KRX-0502 3 g/Day | Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period | 4.08 days | Standard Deviation 2.499 |
| KRX-0502 4 g/Day | Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period | 3.91 days | Standard Deviation 0.98 |
Secondary
Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period
A hospitalization is defined as admission to the hospital.
Time frame: up to Week 48
Population: Per-Protocol Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KRX-0502 3 g/Day | Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period | 13 hospitalizations |
| KRX-0502 4 g/Day | Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period | 10 hospitalizations |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) for Participants Who Entered the Dose Maintenance Period
Treatment-emergent adverse events are defined as adverse events that began after the first administration of study medication or pre-existing conditions that worsened after the first dose of study medication.
Time frame: up to Week 48
Population: Safety Analysis Set: all participants who took at least 1 dose of study medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KRX-0502 3 g/Day | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) for Participants Who Entered the Dose Maintenance Period | 89 Participants |
| KRX-0502 4 g/Day | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) for Participants Who Entered the Dose Maintenance Period | 89 Participants |
Secondary
Time From Randomization to the First Increase From Baseline Hgb of at Least 0.5 Grams Per Deciliter (g/dL) During the Dose Titration Period
The Kaplan-Meier estimator of the survival function of time from randomization to the first increase from Baseline Hgb of at least 0.5 g/dL for each of the two starting dose treatment groups were obtained.
Time frame: from Randomization to Week 24
Population: Per-Protocol Analysis Set. Only participants with data available at Week 24 were analyzed. A participant's time to first hemoglobin value \>= 0.5 above the Baseline value was censored at the study day of the participant's last hemoglobin assessment on or before the Week 24 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KRX-0502 3 g/Day | Time From Randomization to the First Increase From Baseline Hgb of at Least 0.5 Grams Per Deciliter (g/dL) During the Dose Titration Period | 84.0 days |
| KRX-0502 4 g/Day | Time From Randomization to the First Increase From Baseline Hgb of at Least 0.5 Grams Per Deciliter (g/dL) During the Dose Titration Period | 57.0 days |