KRX-0502 (Ferric Citrate) in Subjects With NDD-CKD and IDA (The COMPASS Trial)
- Registration Number
- NCT03236246
- Lead Sponsor
- Keryx Biopharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 206
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 KRX-0502 KRX-0502 1 tablet thrice daily (TID) with meals Group 2 KRX-0502 KRX-0502 2 tablets twice daily (BID) with the largest 2 daily meals
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Number of Hospitalizations for Participants Who Entered the Dose Maintenance Period up to Week 48 A hospitalization is defined as admission to the hospital.
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 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 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 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.
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 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 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 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 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 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 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 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.
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 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 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.
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 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 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.
Duration of Hospitalizations for Participants Who Entered the Dose Maintenance Period up to Week 48 A hospitalization is defined as admission to the hospital.
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 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 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.
Trial Locations
- Locations (24)
Miami Kidney Group
🇺🇸Miami, Florida, United States
Renal Associates, LLC
🇺🇸Columbus, Georgia, United States
Hypertension and Nephrology Association
🇺🇸Eatontown, New Jersey, United States
Southeastern Nephrology Associates
🇺🇸Jacksonville, North Carolina, United States
Metrolina Nephrology Associates, PA
🇺🇸Charlotte, North Carolina, United States
California Institute of Renal Research
🇺🇸Poway, California, United States
South Mississippi Medical Research, LLC
🇺🇸Gulfport, Mississippi, United States
Sierra Nevada Nephrology Consultants
🇺🇸Reno, Nevada, United States
Nephrology Associates, P.C.
🇺🇸Nashville, Tennessee, United States
Southeastern Clinical Research Institute, LLC
🇺🇸Augusta, Georgia, United States
Division of Kidney/HTN Research
🇺🇸Great Neck, New York, United States
Mountain Kidney & Hypertension Associates
🇺🇸Asheville, North Carolina, United States
Research by Design, LLC
🇺🇸Chicago, Illinois, United States
Arizona Kidney Disease and Hypertension center: AKDHC Medical Research Services, LLC
🇺🇸Phoenix, Arizona, United States
Kidney and Hypertension Specialists of Miami, P.A.
🇺🇸Miami, Florida, United States
Eastern Nephrology Associates
🇺🇸New Bern, North Carolina, United States
Columbia Nephrology Associates, PA
🇺🇸Columbia, South Carolina, United States
Research Management, Inc.
🇺🇸Austin, Texas, United States
Southeastern Nephrology
🇺🇸Wilmington, North Carolina, United States
Clinical Advancement Center, PLLC
🇺🇸San Antonio, Texas, United States
P & I Clinical Research, LLC
🇺🇸Lufkin, Texas, United States
Denver Nephrologists, P.C.
🇺🇸Denver, Colorado, United States
South Carolina Nephrology & Hypertension Center, Inc
🇺🇸Orangeburg, South Carolina, United States
Clinical Research Consultants
🇺🇸Kansas City, Missouri, United States