Overview
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.
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
Eligibility
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.