PBF-1681 (Ferric Citrate) for the Treatment of IDA in Patients With NDD-CKD

A Phase 3 Study of PBF-1681 Comprising a 16-week, Placebo-controlled, Double-blind Randomized Period and an 8-week, Open-label Extension Period for the Treatment of Iron Deficiency Anemia in Patients With Non-Dialysis Dependent CKD

To assess the safety and effectiveness of PBF-1681 for the treatment of Iron Deficiency Anemia in patients with Non-Dialysis Dependent Chronic Kidney Disease.

Study Overview

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

Detailed Description

This is a Phase 3, 24-week, multicenter study in Taiwan, comprising a 16-week, randomized, double-blind, placebo-controlled period ("Randomized Period"), followed by an 8-week open-label extension period, where all subjects receive PBF-1681 (ferric citrate) ("Extension Period"). The study will consist of 10 visits over a period of 24 weeks. There will be a screening period of up to 14 days. Approximately 200 subjects will be randomized into the Randomized Period in a 1:1 ratio to receive either PBF-1681 or matching placebo, at baseline.

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Cindy Chiang; Phone Number: 302 +886-2-2655-8218; Email: cchiang@pbf.com.tw
• Study Contact Backup: Name: Raymond Chuang, MS, PMP; Phone Number: 303 +886-2-2655-8218; Email: rchuang@pbf.com.tw

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, 40433
    • Division of Nephrology, Department of Internal Medicine, China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital
  • Taipei, Taiwan, 10002
    • Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital
  • Taipei county, Taiwan, 23561
    • Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho 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. Men or women ≥18 years of age at screening.
2. CKD with eGFR <60 mL/min at screening using the 4-variable Modification of Diet in Renal Disease equation, where up to 20% of subjects with eGFR <15 mL/min are allowed.
3. Hgb ≥9.0 g/dL and ≤11.5 g/dL at screening.
4. Serum ferritin <300 ng/mL and TSAT <30% at screening.
5. Serum iPTH ≤600 pg/mL at screening.
6. Must consume minimally 2 meals per day.
7. Willing to give written informed consent.

8. Women may be enrolled if they are:

   1. Documented to be surgically sterile or postmenopausal (amenorrhea >1 year and follicle-stimulating hormone ≥30 mU/mL), or
   2. Practicing true abstinence for at least 28 days prior to study drug administration until 30 days after study drug administration and having a negative serum pregnancy test at screening, or
   3. Using 2 forms of highly effective contraception, out of which 1 should be a physical barrier (condom or diaphragm), and another method such as adequate hormonal method (eg, contraceptive implants, injectables, oral contraceptives) or non-hormonal methods (eg, intrauterine device, spermicidals) from screening or at least 2 weeks prior to study drug administration (whichever is earlier) until 30 days after the study drug administration and having a negative serum pregnancy test at screening.

Exclusion Criteria:

1. Cause of anemia other than iron deficiency.
2. Serum phosphate <3.5 mg/dL at screening.
3. IV iron administered within 4 weeks of the start of screening.
4. ESA administered within 4 weeks of the start of screening.
5. Blood transfusion within 4 weeks of the start of screening.
6. Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) >3 times upper limit of normal (ULN) at screening.
7. Symptomatic GI bleeding or symptomatic inflammatory bowel disease within 12 weeks of the start of screening.
8. Concurrent GI diseases assessed by Investigators to be inappropriate for the study, eg, acute peptic ulcer, chronic ulcerative colitis, and regional enteritis.
9. Active infection requiring systemic antimicrobial treatment such as antibiotics, antiviral, or antifungals at screening.
10. Concomitant or prior malignancy, except non-melanoma skin cancer or disease-free for ≥2 years after curative therapy.
11. Subjects with known allergic reaction to previous oral iron therapy.
12. Subjects who were intolerant to oral iron therapy.
13. History of hemochromatosis.
14. Scheduled kidney transplant or initiation of dialysis planned within 24 weeks of the start of screening.
15. Planned surgery or hospitalization (anticipated to last >72 hours) during the Randomized Period of the study other than dialysis access-related surgery.
16. Any other medical condition that, in the Investigators' opinion, may disturb subject's completion or optimal participation of the study, act as a significant confounding variable, or carry significant risks to a subject.

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
Experimental: PBF-1681 (ferric citrate); PBF-1681 (ferric citrate) will be dosed two times a day with the 2 largest meals (preferred) or three times a day with meals.	Drug: Ferric citrate; Ferric citrate will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.
Placebo Comparator: Placebo; Matching placebo will be dosed two times a day with the 2 largest meals (preferred) or three times a day with meals.	Drug: Placebo; Matching placebo will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects achieving an increase in Hgb 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 population consisted of all subjects who were randomized, had a baseline laboratory value, took at least 1 dose of study drug or placebo, and had at least 1 post-baseline laboratory assessment during the randomized period.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin (Hgb)	The mean change from baseline to the end of the Randomized Period in Hgb.	16 weeks
Transferring saturation (TSAT)	The mean change from baseline to the end of the Randomized Period in TSAT.	16 weeks
Ferritin	The mean change from baseline to the end of the Randomized Period in ferritin.	16 weeks
Serum Phosphate	The mean change from baseline to the end of the Randomized Period in serum phosphate.	16 weeks
Sustained increase in Hgb of ≥0.75 g/dL	The proportion of subjects achieving a sustained increase in Hgb of ≥0.75 g/dL from baseline over any 4-week interval during the Randomization Period.	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum calcium	The mean change from baseline to the end of the Randomized Period in serum calcium.	16 weeks
Serum bicarbonate	The mean change from baseline to the end of the Randomized Period in serum bicarbonate.	16 weeks
Serum iron	The mean change from baseline to the end of the Randomized Period in serum iron.	16 weeks
Unsaturated iron binding capacity (UIBC)	The mean change from baseline to the end of the Randomized Period in UIBC.	16 weeks
Total iron binding capacity (TIBC)	The mean change from baseline to the end of the Randomized Period in TIBC.	16 weeks
Hematocrit	The mean change from baseline to the end of the Randomized Period in hematocrit.	16 weeks
Intact parathyroid hormone (iPTH)	The mean change from baseline to the end of the Randomized Period in iPTH.	16 weeks
Fibroblast growth factor 23 (intact and C-terminal)	The mean change from baseline to the end of the Randomized Period in FGF23 (intact and C-terminal).	16 weeks
Serum aluminum	The mean change from baseline to the end of the Randomized Period in serum aluminum.	16 weeks
Sustained increase in Hgb	The proportion of subjects achieving a sustained increase in Hgb of ≥0.75 g/dL from baseline over any 4-week interval during the Randomized Period, provided that an increase in Hgb of ≥1.0 g/dL had occurred during that 4-week interval	16 weeks
Increase in Hgb of ≥1.0 g/dL	Time (in days) to first increase in Hgb of ≥1.0 g/dL from baseline.	16 weeks

Collaborators and Investigators

• Sponsor: Panion & BF Biotech Inc.
• Investigators: Study Chair: Mei-I Wu, MD, PhD, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2020
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): December 16, 2022

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

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: PBB00601

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