KRX-0502 (Ferric Citrate) for the Treatment of IDA in Adult Subjects With NDD-CKD

A Phase 3 Study of KRX-0502 (Ferric Citrate) for the Treatment of Iron Deficiency Anemia (IDA) in Adult Subjects With Non-Dialysis Dependent (NDD) Chronic Kidney Disease

a 24-week phase 3, multi-center clinical trial, comprised of a 16-week, randomized, double-blind, placebo-controlled period ("Randomized Period"), followed by an 8-week open-label safety extension period, where all subjects receive KRX-0502 (ferric citrate) ("Extension Period").

Study Overview

• Status: Completed
• Conditions: Anemia of Chronic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: ferric citrate

Detailed Description

a 24-week phase 3, multi-center clinical trial, comprised of a 16-week, randomized, double-blind, placebo-controlled period ("Randomized Period"), followed by an 8-week open-label safety extension period, where all subjects receive KRX-0502 (ferric citrate) ("Extension Period"). The study will consist of 14 clinic visits over a period of 24 weeks. There will be a screening period of up to 14 days; Approximately 230 subjects will be randomized into the Randomized Period in a 1:1 ratio to receive either KRX-0502 or matching placebo, at baseline

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85027
      • AKDHC Medical Research Services, LLC
    • Tempe, Arizona, United States, 85284
      • Southwest Kidney Institute
  • California
    • Glendale, California, United States, 91204
      • California Renal Research
    • La Palma, California, United States, 90623
      • Southern California Medical Research Center
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute, Inc
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • Sacramento, California, United States, 95825
      • Capital Nephrology Medical Group
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
    • San Diego, California, United States, 92103
      • La Jolla Clinical Research, Inc
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Nephrology
  • Florida
    • DeLand, Florida, United States, 32123
      • Creekside Medical Research
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research, Inc
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Kidney Care Associates, LLC
    • Macon, Georgia, United States, 31217
      • Renal Physicians of Georgia, PC
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Pacific Renal Research Institute
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Advanced Renal Care
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Research Institute
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Renal Associates of Baton Rouge
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Western new England Renal & Transplant Associates
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Renaissance Renal Research
    • Pontiac, Michigan, United States, 48341
      • Michigan Kidney Consultants, PC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants
  • Nebraska
    • Lincoln, Nebraska, United States, 68105
      • Lincoln Nephrology & Hypertension
  • Nevada
    • Reno, Nevada, United States, 89519
      • Sierra Nevada Nephrology Asoociates
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney & Hypertension Associates
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Nephrology
  • Texas
    • Austin, Texas, United States, 78758
      • Research Management, Inc.
    • Austin, Texas, United States, 78732
      • Research Management, Inc
    • Lufkin, Texas, United States, 75904
      • TAD Clinical Research
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center
    • San Antonio, Texas, United States, 78215
      • Clinical Advancement Center
    • San Antonio, Texas, United States, 78207
      • Kidney & Hypertension Specialists
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Mendez Center for Clinical Research
    • Fairfax, Virginia, United States, 22033
      • Nephrology Associates of Northern VA, Inc.
    • Hampton, Virginia, United States, 23666
      • Peninsula Kidney Associates

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:

1. Men and non-lactating women with negative serum pregnancy test (for women of child-bearing potential) at Screening
2. Age ≥18 years
3. CKD with Estimated Glomerular Filtration Rate (eGFR) <60 mL/min at Screening using the 4-variable Modification of Diet in Renal Disease (MDRD) equation (with a limit of up to 20% of the target randomization of 230 subjects with eGFR <15 mL/min)
4. Patients who were intolerant of or have had an inadequate therapeutic response to oral iron supplements (in the opinion of the investigator)
5. Hgb ≥ 9.0 g/dL and ≤11.5 g/dL at Screening
6. Serum ferritin ≤200 ng/mL and Transferrin Saturation (TSAT) ≤25% at Screening
7. Serum Intact Parathyroid Hormone (iPTH) ≤600 pg/mL at Screening
8. Must consume a minimum of 2 meals per day
9. Willing and able to give written informed consent

Exclusion Criteria:

1. Serum phosphate <3.5 mg/dL at Screening
2. Liver enzymes (ALT/AST) >X3 times upper limit of normal at Screening
3. Symptomatic gastrointestinal bleeding or inflammatory bowel disease within 12 weeks prior to Screening
4. Evidence of acute kidney injury or requirement for dialysis within 12 weeks prior to Screening
5. Scheduled kidney transplant or initiation of dialysis planned within 24 weeks of Screening
6. IV iron administered within 4 weeks prior to Screening
7. Erythropoiesis-stimulating agent (ESA) administered within 4 weeks prior to Screening
8. Blood transfusion within 4 weeks prior to Screening
9. Receipt of any investigational drug within 4 weeks prior to Screening
10. Cause of anemia other than iron deficiency or chronic kidney disease
11. Malignancy (except non-melanoma skin cancer or disease-free for ≥2 years after curative therapy)
12. History of hemochromatosis
13. Active drug or alcohol dependence or abuse (excluding tobacco use or medicinal marijuana) within the 12 months prior to Screening or evidence of such abuse (in the opinion of the PI)
14. Subjects with known allergic reaction to previous oral iron therapy
15. Previous intolerance to oral ferric citrate
16. Psychiatric disorder that interferes with the subject's ability to comply with the study protocol
17. Planned surgery or hospitalization (anticipated to last >72 hours) during the randomized period of the trial other than dialysis access related surgery.
18. Any other medical condition that, in the opinion of the PI, renders the subject unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the subject
19. Inability to cooperate with study personnel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching Placebo	Drug: Placebo; Matching placebo
Experimental: KRX-0502 (ferric citrate); 1 g of KRX-0502 (ferric citrate) containing approximately 210 mg of ferric iron	Drug: ferric citrate; 1 g ferric citrate containing approximately 210 mg of ferric iron; Other Names: KRX-0502

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving an Increase in Hemoglobin of ≥1.0 g/dL at Any Time Point Between Baseline and the End of the 16-week Randomized Period	Efficacy analyses were performed for the Intention-to-treat (ITT) population, the population consisted of all subjects who were randomized, had a baseline laboratory value, took at least 1 dose of study drug, and had at least 1 post-baseline laboratory assessment during the randomized period.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Hemoglobin (Hgb) at the End of 16 Weeks Minus Baseline	The difference of Hgb at 16 weeks compared to the Hgb value at the time of study entry.	Baseline and week 16
Mean Change in Transferrin Saturation (TSAT) at the End of 16 Weeks Minus Baseline	The difference of TSAT at 16 weeks compared to the TSAT value at the time of study entry was averaged.	Baseline and week 16
Mean Change in Ferritin at the End of 16 Weeks Minus Baseline	The difference of ferritin at 16 weeks compared to the ferritin value at the time of study entry.	Baseline and week 16
Percentage of Subjects Experiencing a Sustained Treatment Effect on Hemoglobin (Hgb)	Proportion of subjects that continued to maintain an increase in Hgb over a 4 week period, provided they had an increase of at least 1.0 g/dL during that 4-week period	Week 16
Mean Change in Serum Phosphate at the End of 16 Weeks Minus Baseline	The difference of serum phosphate at 16 weeks compared to the serum phosphate value at the time of study entry.	Baseline and week 16

Collaborators and Investigators

• Sponsor: Keryx Biopharmaceuticals
• Investigators: Study Chair: Geoffrey Block, MD, Denver Nephrology; Study Chair: Glenn Chertow, MD, Division of Nephrology at Stanford University School of Medicine; Study Chair: Steven Fishbane, MD, Kidney Disease and Hypertension at North Shore University Hospital/Long Island Jewish Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 11, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 20, 2014

Study Record Updates

• Last Update Posted (Actual): March 22, 2018
• Last Update Submitted That Met QC Criteria: February 22, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Anemia; Chronic kidney disease; ferric citrate
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: KRX-0502-306