Chronic Kidney Diseases
Conditions
Keywords
Pediatric, CKD, Phosphate Binder
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
Interventions
DRUGFerric Citrate
Auryxia® 210 mg ferric iron tablets equivalent to 1 g of FC will be supplied as 200 tablets in 400cc high-density polyethylene bottles.
DRUGPlacebo
Placebo to match Ferric Citrate tablets
Sponsors
University of California, Los Angeles
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 6 to 18 years (inclusive); 2. 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 3. Serum phosphate \<=5.9 mg/dl; 4. Serum ferritin \<500 ng/ml and TSAT \<50%; 5. 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; 6. Able to swallow tablets; 7. Able to eat at least two meals a day; 8. 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
1. Patients currently treated with phosphate binders. 2. History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo) 3. Current intestinal malabsorption, documented in the medical record; disease, inflammatory bowel syndrome, and/or Crohn's Disease. 4. Anticipated initiation of dialysis or kidney transplantation within 6 months 5. Current or planned future systemic immunosuppressive therapy 6. Prior solid organ transplantation 7. Receipt of bone marrow transplant within two years of screening 8. Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol 9. Patients participating in other interventional study (observational study participation permitted) 10. Poor adherence to medical treatments in the opinion of the investigator 11. Cystinosis 12. Fanconi syndrome 13. Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada, United States
Contacts
CONTACTJENNY BROOK, MS
CONTACTBarbara Gales, RN
PRINCIPAL_INVESTIGATORIsidro B Salusky, MD
University of California, Los Angeles
Outcome results
None listed