Ferric Citrate and Chronic Kidney Disease in Children

Study Overview
=================
Brief Summary
-----------------
We will conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6-17 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 12 core clinical sites.

Detailed Description
-----------------
We will conduct a double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) aged 6-17 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 12 core clinical sites. Schedule of Intervention: During the 12-month trial, participants will be given a daily fixed weight-based dose of FC. Schedule for data collection/analyses to be performed: Blood for primary outcome assessments will be collected at screening, baseline and at months 1, 2, 3, 6, 9, 12. Blood for safety assessments will be collected at the same intervals. The primary analyses for this 2-arm trial will evaluate changes from baseline in iFGF23 levels over 12 months between the treatment and the placebo arms. The analysis will use a linear mixed-effects model, with random participant effects accounting for repeated measurements, random site effects accounting for clustering of participants into study sites, and a fixed treatment effect, which interacts with a time indicator (Months 3-12 vs. Months 1-3). Primary objectives: To assess the effects of therapy with FC on changes in iFGF23 levels To determine safety and tolerability of FC. Secondary objectives: • To assess the effects of FC on anemia and indices of mineral and bone metabolism. Primary Endpoint: • Change in iFGF23 level Safety and Tolerability Endpoints: • Ability to safely tolerate FC Secondary Endpoints: Change in anemia Change in the indices of mineral and bone metabolism This is a Phase 2 study with participation from 12 sites that will take 36 months to complete enrollment and a total of 48 months to complete data collection with each participant being part of the study for 12 months. Study website: fit4kid.dgsom.ucla.edu

Official Title
-----------------
Phosphate Binder Therapy and Chronic Kidney Disease in Children

Conditions
-----------------
Chronic Kidney Diseases

Intervention / Treatment
-----------------
* Drug: Ferric Citrate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages 6 to 17 years (inclusive); Estimated GFR of 15-59 ml/min per 1.73 m2 by modified CKiD formula;56 Serum phosphate within age appropriate normal levels; Serum ferritin <500 ng/ml and TSAT <50%; For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or ESAs such treatments must have stable dosing for at least 2 weeks prior to screening; Able to swallow tablets; Able to eat at least two meals a day; In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations. Exclusion Criteria: Perform physical exam and obtain vitals. Check urine pregnancy test in menstruating female participants and administer corresponding questionnaire. Administer GI Symptom questionnaire. Ascertain AEs. Obtain information on concomitant medications. Process 24-hour urine sample for 24 hour urine creatinine and phosphate. Measure run-in adherence using eCAP system and pill count. Administer the Medical Adherence Measure tool. Reinforce adherence. Prepare one month's supply of drug and enter them into eCAP system.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>During the 12-month trial, participants will be given a fixed weight-based dose of Ferric Citrate (FC). The full medication dose will be 3g/day for participants weighing <31 kg, 5g/day for those weighing >31 - <51 kg, and 6g/day for participants >51 kg. These doses will be divided into three doses to be taken with meals. | Drug: Ferric Citrate<br>* Auryxia® 210 mg ferric iron tablets equivalent to 1 g of FC and matching placebo will be supplied as 200 tablets in 400cc high-density polyethylene bottles.<br>* Other names: Auryxia;|
| Placebo Comparator: Control Arm<br>During the 12-month trial, participants will be given a fixed weight-based dose of Placebo. The full medication dose will be 3g/day for participants weighing <31 kg, 5g/day for those weighing >31 - <51 kg, and 6g/day for participants >51 kg. These doses will be divided into three doses to be taken with meals. | Drug: Placebo<br>* Placebo to match Ferric Citrate tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iFGF23 levels | Change in iFGF23 levels | 6 months and 12 months | 
| Safety of Ferric Citrate | Safety of FC will be compared to Placebo through measures of Adverse Events | 12 months | 
| Tolerability of Ferric Citrate | Tolerability of FC will be compared to Placebo through measures of Adverse Events | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects on Hemoglobin | Increase in Hemoglobin will be compared between FC and Placebo | 12 months | 
| Effects on TSAT | Increase in TSAT will be compared between FC and Placebo | 12 months | 
| Effects on Ferritin | Increase in Ferritin will be compared between FC and Placebo | 12 months | 
| Effects on PTH | Increase in PTH will be compared between FC and Placebo | 12 months | 
| Effects on 1,25 D | Decrease in 1,25 D will be compared between FC and Placebo | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pediatric, CKD, Phosphate Binder