Ferric Citrate and Chronic Kidney Disease in Children
- Registration Number
- NCT04741646
- Lead Sponsor
- University of California, Los Angeles
- 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 6-18 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 20 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 6-18 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 20 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 3, 6, 9, 12. Blood for safety assessments will be collected at the the months 1, 2, 3, 6, 9, 12.
The primary analyses for this 2-arm trial will compare log-transformed iFGF23 values over 12 months between the treatment and the placebo arms. The analysis will use a linear mixed-effects model, including stratification factors CKD stage and urine protein to creatinine ratio, with random participant effects accounting for repeated measurements, and a fixed treatment effect, which interacts with a time indicator (Months 3-12 vs. Baseline/Screening).
Primary objectives:
* To assess the effects of therapy with FC on 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:
• iFGF23 level
Safety and Tolerability Endpoints:
• Ability to safely tolerate FC
Secondary Endpoints:
* Anemia
* Indices of mineral and bone metabolism
This is a Phase 2 study with participation from 20 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
- Ages 6 to 18 years (inclusive);
- Estimated Glomerular Filtration Rate (GFR) of 15-59 ml/min per 1.73 m2 by modified Chronic Kidney disease in Children (CKiD) under 25 (U25) formula;56
- Serum phosphate <=5.9 mg/dl;
- Serum ferritin <500 ng/ml and TSAT <50%;
- For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or erythropoiesis-stimulating agents (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.
- Patients currently treated with phosphate binders.
- History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
- Current intestinal malabsorption, documented in the medical record; disease, inflammatory bowel syndrome, and/or Crohn's Disease.
- Anticipated initiation of dialysis or kidney transplantation within 6 months
- Current or planned future systemic immunosuppressive therapy
- Prior solid organ transplantation
- Receipt of bone marrow transplant within two years of screening
- Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
- Patients participating in other interventional study (observational study participation permitted)
- Poor adherence to medical treatments in the opinion of the investigator
- Cystinosis
- Fanconi syndrome
- Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm Ferric Citrate 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. Control Arm Placebo 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.
- Primary Outcome Measures
Name Time Method iFGF23 levels 12 months Compared to placebo, active treatment with FC will lower iFGF23 levels
Safety of Ferric Citrate 12 months Comparing proportion of subjects with AE and SAE between arms
Tolerability of Ferric Citrate 12 months Compared with placebo, active treatment will be tolerable
- Secondary Outcome Measures
Name Time Method Effects on Transferrin Saturation (TSAT) 12 months Compared with placebo, active treatment with FC will be associated with larger increase in hemoglobin, higher TSAT and higher Ferritin from baseline
Effects on PTH and 1,25 D 12 months Compared to placebo, active treatment with FC will be associated with a larger decrease in PTH and larger increase in 1,25 D from baseline
Trial Locations
- Locations (20)
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Indiana U
🇺🇸Indianapolis, Indiana, United States
Children's Mercy Hospital, Kansas City
🇺🇸Kansas City, Missouri, United States
Washington U
🇺🇸Saint Louis, Missouri, United States
Cohen's Childrens
🇺🇸New York, New York, United States
Children's Hospital at Montefiore
🇺🇸The Bronx, New York, United States
Duke
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Nationwide Children's
🇺🇸Columbus, Ohio, United States
OHSU
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Medical Center, Dallas
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
UTH
🇺🇸Houston, Texas, United States
BC Children's Hospital Research Institute
🇨🇦Vancouver, British Columbia, Canada
SickKids
🇨🇦Toronto, Ontario, Canada