Study to Evaluate the Safety and Tolerability of Ferric Citrate in Children With Hyperphosphatemia Related to Chronic Kidney Disease

Study Overview
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Brief Summary
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This study will be conducted to assess the safety and tolerability of ferric citrate in pediatric participants with hyperphosphatemia related to chronic kidney disease (CKD).

Official Title
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A 36-week, Single-Arm, Open-label Study to Evaluate the Safety and Tolerability of Ferric Citrate in Children With Hyperphosphatemia Related to Chronic Kidney Disease

Conditions
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Hyperphosphatemia Related to Chronic Kidney Disease

Intervention / Treatment
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* Drug: ferric citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight ≥ 40 kilograms (kg) (dry weight for dialysis participants) at Screening Chronic kidney disease (CKD) requiring chronic dialysis (i.e., hemodialysis or peritoneal dialysis), or CKD not on dialysis with an estimated glomerular filtration rate (eGFR) <30 milliliters per minute (mL/min)/1.73 meters squared (m^2) at Screening Documented history of CKD-related hyperphosphatemia for at least 3 months prior to the screening visit. If participant is on phosphate binder(s) after at least 1 week of washout (i.e., at Visit 1a or Visit 1b) or if participant is not on phosphate binder(s) at Visit 1, serum phosphorus must be: 12 years: >5.8 milligrams per deciliter (mg/dL). 13 to <17 years: >4.5 mg/dL. Transferrin saturation (TSAT) <50%. Serum ferritin <500 nanograms per milliliter (ng/mL). Parent/legal guardian must be willing and able to give written informed consent, and child (participant) willing and able to give age-appropriate assent according to local regulatory requirements. Female participants of childbearing potential, defined as post menarche and not surgically sterile, must have a negative serum pregnancy test. Dialysis adequacy stable for at least 2 months prior to screening and agree to maintain dialysis prescription for the duration of the pharmacodynamic assessment period unless changes are needed for safety. A minimum dialysis adequacy (dialysis clearance of urea-dialysis time/volume of distribution of urea [Kt/V]), defined by the following: Hemodialysis adequacy: single-pool Kt/V ≥1.2 for at least 1 hemodialysis session within 2 months. Peritoneal dialysis: Kt/V ≥1.8 (or per local guidance) within 4 months. Exclusion Criteria: Active significant gastrointestinal (GI) disorder, including overt GI bleeding or active inflammatory bowel disease Liver transaminases (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) >3× the upper limit of normal at Screening Unable to swallow pills, if participant requires tube feeding, ferric citrate must be taken orally and not administered via feeding tube). Non-renal cause of hyperphosphatemia Active drug or alcohol dependence or abuse (excluding tobacco use or medicinal marijuana) within the 12 months prior to Screening or evidence of such abuse (in the opinion of the Investigator) Malignancy, except for participants who have been disease-free for at least 2 years after curative therapy Participants with a functioning organ transplant A known allergy or intolerance to ferric citrate or any of its constituents Participants who do not agree to remain abstinent or assent to use a combination of 2 of the following highly effective birth control methods for at least 28 days before the first dose, during the study (including during dose interruptions), and for at least 30 days after the last dose: Barrier method of contraception: condoms (female or male) with or without a spermicidal agent, diaphragm, or cervical cap with spermicide. Intrauterine device (IUD). Hormone-based contraceptives which are associated with inhibition of ovulation Females who are pregnant or breast-feeding. Any other medical condition that, in the opinion of the Investigator, renders the participant unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the participant The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study Receipt of any investigational drug within 4 weeks before Screening History of hemochromatosis or iron overload syndrome (e.g., hereditary sideroblastic anemia, thalassemia)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferric citrate<br>Participants aged 12 to < 17 years will receive ferric citrate for 36 weeks at a starting dose based on body weight categories. | Drug: ferric citrate<br>* oral tablets<br>* Other names: KRX-0502;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with serious and non-serious treatment-emergent adverse events (AEs) including gastrointestinal (GI) AEs of special interest |  | up to Week 40 | 
| Number of participants with clinically significant laboratory abnormalities |  | up to Week 40 | 
| Number of participants with treatment-emergent adverse events leading to the discontinuation of ferric citrate |  | up to Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum phosphorus to Week 12/early termination (ET) |  | Baseline; up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperphosphatemia, chronic kidney disease, CKD, ferric citrate, pediatric, dialysis