PBF-1681 (Ferric Citrate) for the Treatment of IDA in Patients With NDD-CKD
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
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Outcome Measures
Primary Outcome Measures
- 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. [16 weeks]
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.
Secondary Outcome Measures
- Hemoglobin (Hgb) [16 weeks]
The mean change from baseline to the end of the Randomized Period in Hgb.
- Transferring saturation (TSAT) [16 weeks]
The mean change from baseline to the end of the Randomized Period in TSAT.
- Ferritin [16 weeks]
The mean change from baseline to the end of the Randomized Period in ferritin.
- Serum Phosphate [16 weeks]
The mean change from baseline to the end of the Randomized Period in serum phosphate.
- Sustained increase in Hgb of ≥0.75 g/dL [16 weeks]
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.
Other Outcome Measures
- Serum calcium [16 weeks]
The mean change from baseline to the end of the Randomized Period in serum calcium.
- Serum bicarbonate [16 weeks]
The mean change from baseline to the end of the Randomized Period in serum bicarbonate.
- Serum iron [16 weeks]
The mean change from baseline to the end of the Randomized Period in serum iron.
- Unsaturated iron binding capacity (UIBC) [16 weeks]
The mean change from baseline to the end of the Randomized Period in UIBC.
- Total iron binding capacity (TIBC) [16 weeks]
The mean change from baseline to the end of the Randomized Period in TIBC.
- Hematocrit [16 weeks]
The mean change from baseline to the end of the Randomized Period in hematocrit.
- Intact parathyroid hormone (iPTH) [16 weeks]
The mean change from baseline to the end of the Randomized Period in iPTH.
- Fibroblast growth factor 23 (intact and C-terminal) [16 weeks]
The mean change from baseline to the end of the Randomized Period in FGF23 (intact and C-terminal).
- Serum aluminum [16 weeks]
The mean change from baseline to the end of the Randomized Period in serum aluminum.
- Sustained increase in Hgb [16 weeks]
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
- Increase in Hgb of ≥1.0 g/dL [16 weeks]
Time (in days) to first increase in Hgb of ≥1.0 g/dL from baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men or women ≥18 years of age at screening.
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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.
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Hgb ≥9.0 g/dL and ≤11.5 g/dL at screening.
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Serum ferritin <300 ng/mL and TSAT <30% at screening.
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Serum iPTH ≤600 pg/mL at screening.
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Must consume minimally 2 meals per day.
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Willing to give written informed consent.
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Women may be enrolled if they are:
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Documented to be surgically sterile or postmenopausal (amenorrhea >1 year and follicle-stimulating hormone ≥30 mU/mL), or
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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
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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:
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Cause of anemia other than iron deficiency.
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Serum phosphate <3.5 mg/dL at screening.
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IV iron administered within 4 weeks of the start of screening.
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ESA administered within 4 weeks of the start of screening.
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Blood transfusion within 4 weeks of the start of screening.
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Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) >3 times upper limit of normal (ULN) at screening.
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Symptomatic GI bleeding or symptomatic inflammatory bowel disease within 12 weeks of the start of screening.
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Concurrent GI diseases assessed by Investigators to be inappropriate for the study, eg, acute peptic ulcer, chronic ulcerative colitis, and regional enteritis.
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Active infection requiring systemic antimicrobial treatment such as antibiotics, antiviral, or antifungals at screening.
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Concomitant or prior malignancy, except non-melanoma skin cancer or disease-free for ≥2 years after curative therapy.
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Subjects with known allergic reaction to previous oral iron therapy.
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Subjects who were intolerant to oral iron therapy.
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History of hemochromatosis.
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Scheduled kidney transplant or initiation of dialysis planned within 24 weeks of the start of screening.
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Planned surgery or hospitalization (anticipated to last >72 hours) during the Randomized Period of the study other than dialysis access-related surgery.
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung | Taiwan | 80756 | |
2 | Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital | Kaohsiung | Taiwan | 83301 | |
3 | Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital | Keelung | Taiwan | 20401 | |
4 | Division of Nephrology, Department of Internal Medicine, Far East Memorial Hospital | New Taipei City | Taiwan | 22060 | |
5 | Division of Nephrology, Department of Internal Medicine, China Medical University Hospital | Taichung | Taiwan | 40433 | |
6 | Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital | Taipei county | Taiwan | 23561 | |
7 | Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital | Taipei | Taiwan | 10002 | |
8 | Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital | Taipei | Taiwan | 11217 |
Sponsors and Collaborators
- Panion & BF Biotech Inc.
Investigators
- Principal Investigator: Der-Cherng Tarng, MD, PhD, Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PBB00601