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

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

• Men or women ≥18 years of age at screening.
• 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.
• Hgb ≥9.0 g/dL and ≤11.5 g/dL at screening.
• Serum ferritin <300 ng/mL and TSAT <30% at screening.
• Serum iPTH ≤600 pg/mL at screening.
• Must consume minimally 2 meals per day.
• Willing to give written informed consent.
• Women may be enrolled if they are:

• Documented to be surgically sterile or postmenopausal (amenorrhea >1 year and follicle-stimulating hormone ≥30 mU/mL), or
• 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
• 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

• Cause of anemia other than iron deficiency.
• Serum phosphate <3.0 mg/dL at screening.
• IV iron administered within 4 weeks of the start of screening.
• ESA administered within 4 weeks of the start of screening.
• Blood transfusion within 4 weeks of the start of screening.
• Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) >3 times upper limit of normal (ULN) at screening.
• Symptomatic GI bleeding or symptomatic inflammatory bowel disease within 12 weeks of the start of screening.
• Concurrent GI diseases assessed by Investigators to be inappropriate for the study, eg, acute peptic ulcer, chronic ulcerative colitis, and regional enteritis.
• Active infection requiring systemic antimicrobial treatment such as antibiotics, antiviral, or antifungals at screening.
• Concomitant or prior malignancy, except non-melanoma skin cancer or disease-free for ≥2 years after curative therapy.
• Subjects with known allergic reaction to previous oral iron therapy.
• Subjects who were intolerant to oral iron therapy.
• History of hemochromatosis.
• Scheduled kidney transplant or initiation of dialysis planned within 24 weeks of the start of screening.
• Planned surgery or hospitalization (anticipated to last >72 hours) during the Randomized Period of the study other than dialysis access-related surgery.
• 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.