KRX-0502 (Ferric Citrate) in Subjects With NDD-CKD and IDA (The COMPASS Trial)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Study of KRX-0502 (Ferric Citrate) Dose Regimens in Subjects With Non-Dialysis Dependent Chronic Kidney Disease and Iron-Deficiency Anemia

Conditions
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Chronic Kidney Diseases, Iron Deficiency Anemia

Intervention / Treatment
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* Drug: KRX-0502


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>KRX-0502 1 tablet thrice daily (TID) with meals | Drug: KRX-0502<br>* Oral ferric citrate with meals<br>* Other names: ferric citrate;|
| Experimental: Group 2<br>KRX-0502 2 tablets twice daily (BID) with the largest 2 daily meals | Drug: KRX-0502<br>* Oral ferric citrate with meals<br>* Other names: ferric citrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline; Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline; Week 48 | 
| 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. | from Randomization to Week 24 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; up to Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| 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. | Baseline; Week 24 | 
| 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. | Baseline; Week 48 | 
| Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period | A hospitalization is defined as admission to the hospital. | up to Week 48 | 
| Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period | A hospitalization is defined as admission to the hospital. | up to Week 48 | 
| 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. | up to Week 48 |