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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Anemia of Chronic Kidney Disease

Intervention / Treatment
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* Drug: Ferric citrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 <3.5 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PBF-1681 (ferric citrate)<br>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<br>* Ferric citrate will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.<br>|
| Placebo Comparator: Placebo<br>Matching placebo will be dosed two times a day with the 2 largest meals (preferred) or three times a day with meals. | Drug: Placebo<br>* Matching placebo will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ferric Citrate, Anemia, Chronic Kidney Disease