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

Anemia of Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04543812
• Other study ID #: PBB00601
• Status: Completed
• Phase: Phase 3
• Start date: October 14, 2020
• Est. completion date: December 16, 2022

Study information

• Verified date: March 2023
• Source: Panion & BF Biotech Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: December 16, 2022
• Est. primary completion date: October 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia of Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Ferric citrate
Ferric citrate will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.
• Placebo
Matching placebo will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.

Locations

Country	Name	City	State
Taiwan	Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital	Kaohsiung
Taiwan	Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital	Keelung
Taiwan	Division of Nephrology, Department of Internal Medicine, Far East Memorial Hospital	New Taipei City
Taiwan	Division of Nephrology, Department of Internal Medicine, China Medical University Hospital	Taichung
Taiwan	Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital	Taipei
Taiwan	Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital	Taipei
Taiwan	Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital	Taipei county

Sponsors (1)

Lead Sponsor	Collaborator
Panion & BF Biotech Inc.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum calcium	The mean change from baseline to the end of the Randomized Period in serum calcium.	16 weeks
Other	Serum bicarbonate	The mean change from baseline to the end of the Randomized Period in serum bicarbonate.	16 weeks
Other	Serum iron	The mean change from baseline to the end of the Randomized Period in serum iron.	16 weeks
Other	Unsaturated iron binding capacity (UIBC)	The mean change from baseline to the end of the Randomized Period in UIBC.	16 weeks
Other	Total iron binding capacity (TIBC)	The mean change from baseline to the end of the Randomized Period in TIBC.	16 weeks
Other	Hematocrit	The mean change from baseline to the end of the Randomized Period in hematocrit.	16 weeks
Other	Intact parathyroid hormone (iPTH)	The mean change from baseline to the end of the Randomized Period in iPTH.	16 weeks
Other	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
Other	Serum aluminum	The mean change from baseline to the end of the Randomized Period in serum aluminum.	16 weeks
Other	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
Other	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
Primary	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	Hemoglobin (Hgb)	The mean change from baseline to the end of the Randomized Period in Hgb.	16 weeks
Secondary	Transferring saturation (TSAT)	The mean change from baseline to the end of the Randomized Period in TSAT.	16 weeks
Secondary	Ferritin	The mean change from baseline to the end of the Randomized Period in ferritin.	16 weeks
Secondary	Serum Phosphate	The mean change from baseline to the end of the Randomized Period in serum phosphate.	16 weeks
Secondary	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