Assess the Safety and Efficacy of Nephoxil® in Subjects With End Stage Renal Disease (ESRD) on Dialysis

A Long-Term, Open-Label, Prospective Phase IV Study to Assess the Safety and Efficacy of Nephoxil® in Subjects With End Stage Renal Disease (ESRD) on Dialysis

To assess the long-term safety and effectiveness of Nephoxil® for the treatment of hyperphosphatemia in patients with ESRD undergoing dialysis.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic; Hyperphosphatemia; Phosphorus Metabolism Disorders; End-stage Renal Disease
• Intervention / Treatment: Drug: Ferric Citrate

Detailed Description

This study is an open-label, prospective, long term, Phase IV study to assess the safety and efficacy of Nephoxil® in subjects with ESRD on dialysis.

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan, 83301
    • Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital
  • Keelung, Taiwan, 20401
    • Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital
  • New Taipei City, Taiwan, 22060
    • Division of Nephrology, Department of Internal Medicine, Far East Memorial Hospital
  • Taichung, Taiwan, 40705
    • Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • Division of Nephrology, Department of Internal medicine, National Taiwan University Hospital
  • Taipei, Taiwan, 11042
    • Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital
  • Taipei, Taiwan, 11101
    • Division of Nephrology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital
  • Taipei, Taiwan, 11217
    • Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital

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. Is ≧ 18 years of age on the day of signing informed consent or other age required by local regulation
2. Willing and able to provide written informed consent
3. ESRD patients who is undergoing hemodialysis 3 times per week and is considered necessary to receive medication for hyperphosphatemia by his/her treating physician
4. Serum ferritin <1000 ng/mL and transferrin saturation (TSAT) < 50% at the Enrollment Visit
5. Women of child-bearing potential (WOCBP [defined as women ≤ 50 years of age with a history of amenorrhea for < 12 months prior to study entry]) who is willing to use an effective form of contraception during study participation

Exclusion Criteria:

1. Has any known contraindication to ferric citrate according to locally approved prescribing information, include but not limited to the following criteria:

   i. Is allergic to ferric citrate ii. Has hypophosphatemia iii. Has hemochromatosis or iron overload syndromes iv. Has active severe GI disorders

2. Has parathyroidectomy (PTx) or percutaneous ethanol injection therapy (PEIT) within 3 months prior to Enrollment Visit or serum calcium < 7 mg/dL at the Enrollment Visit
3. Has participated in another interventional study for any investigational agent or device within 30 days prior to enrollment
4. Is currently pregnant or breastfeeding
5. Other unstable medical condition or psychiatric conditions that is considered unsuitable for this study per Investigator's clinical judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferric citrate; Ferric Citrate (Nephoxil® Capsules) will be dosed three times a day (with meals).	Drug: Ferric Citrate; Ferric citrate will be provided as a 500mg capsule. All intervention doses will be based on serum phosphorus levels.; Other Names: Nephoxil® Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment-emergent adverse events (TEAEs)	Number of subjects with treatment-emergent adverse events (TEAEs)	13 months
Percentage of subjects with treatment-emergent adverse events (TEAEs)	Percentage of subjects with treatment-emergent adverse events (TEAEs)	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Phosphorus	Serum Phosphorus will be assessed by time-course changes of serum phosphorus levels and proportion of subjects achieved target range of serum phosphorus (>=3.5 mg/dL and <=5.5. mg/dL) from baseline to the end-of-treatment.	13 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum calcium	Time-course changes of serum calcium from baseline.	13 months
Intact plasma parathyroid hormone (iPTH)	Time-course changes of intact plasma parathyroid hormone (iPTH) from baseline.	13 months
Ferritin	Time-course changes of ferritin from baseline.	13 months
Transferring saturation (TSAT) percentage	Time-course changes of transferring saturation (TSAT) percentage from baseline.	13 months
Serum iron	Time-course changes of serum iron from baseline.	13 months
Total iron-binding capacity (TIBC)	Time-course changes of total iron-binding capacity (TIBC) from baseline.	13 months
Hemoglobin	Time-course changes of hemoglobin from baseline.	13 months
Dose of IV iron	Time-course changes of dose of IV iron from baseline.	13 months
Dose of erythropoiesis stimulating agents (ESA)	Time-course changes of dose of erythropoiesis stimulating agents (ESA) from baseline.	13 months
Treatment adherence	Prescribed dose and the dose actually taken at each time point will be calculated.	13 months

Collaborators and Investigators

• Sponsor: Panion & BF Biotech Inc.
• Investigators: Principal Investigator: Mai-Szu Wu, M.D., Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital

Publications and helpful links

General Publications

• Lee CT, Lee CC, Wu MJ, Chiu YW, Leu JG, Wu MS, Peng YS, Wu MS, Tarng DC. Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial. PLoS One. 2022 Mar 3;17(3):e0264727. doi: 10.1371/journal.pone.0264727. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 12, 2017
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ACTUAL): May 31, 2019

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: August 20, 2017
• First Posted (ACTUAL): August 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Dialysis; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Hemodialysis; Renal Failure; Kidney Failure; Metabolic Disease; Anticoagulants; Citric Acid; Ferric Compounds; Calcium Chelating Agents; Chelating Agents; Sequestering Agents
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency; Metabolic Diseases; Hyperphosphatemia; Phosphorus Metabolism Disorders
• Other Study ID Numbers: PBB00501

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No