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

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Iron Deficiency Anemia
• Intervention / Treatment: Drug: KRX-0502

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.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Arizona Kidney Disease and Hypertension center: AKDHC Medical Research Services, LLC
  • California
    • Chula Vista, California, United States, 91910
      • California Institute of Renal Research
    • El Centro, California, United States, 92243
      • California Institute of Renal Research
    • Poway, California, United States, 92064
      • California Institute of Renal Research
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Nephrologists, P.C.
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Kidney Group
    • Miami, Florida, United States, 33150
      • Kidney and Hypertension Specialists of Miami, P.A.
  • Georgia
    • Augusta, Georgia, United States, 30904
      • Southeastern Clinical Research Institute, LLC
    • Columbus, Georgia, United States, 31904
      • Renal Associates, LLC
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
  • Mississippi
    • Gulfport, Mississippi, United States, 39501
      • South Mississippi Medical Research, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants
  • Nevada
    • Reno, Nevada, United States, 89511
      • Sierra Nevada Nephrology Consultants
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Hypertension and Nephrology Association
  • New York
    • Great Neck, New York, United States, 11021
      • Division of Kidney/HTN Research
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney & Hypertension Associates
    • Charlotte, North Carolina, United States, 28207
      • Metrolina Nephrology Associates, PA
    • Greenville, North Carolina, United States, 27834
      • Eastern Nephrology Associates
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Nephrology Associates
    • New Bern, North Carolina, United States, 28562
      • Eastern Nephrology Associates
    • Wilmington, North Carolina, United States, 28401
      • Southeastern Nephrology
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, PA
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology & Hypertension Center, Inc
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates, P.C.
  • Texas
    • Austin, Texas, United States, 78758
      • Research Management, Inc.
    • Austin, Texas, United States, 78751
      • Research Management, Inc.
    • Lufkin, Texas, United States, 75904
      • P & I Clinical Research, LLC
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Keryx Biopharmaceuticals
• Investigators: Study Director: Medical Director, Keryx Biopharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2017
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): September 27, 2019

Study Registration Dates

• First Submitted: July 26, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (Actual): August 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Anemia, Hypochromic; Iron Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Anemia, Iron-Deficiency; Anemia
• Other Study ID Numbers: KRX-0502-402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No