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.

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.

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 <3.0 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.