Ferric Citrate and Chronic Kidney Disease in Children

Phase 2RecruitingNCT04741646

University of California, Los Angeles160 enrolled

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 6-18 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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Conditions

Chronic Kidney Diseases

Interventions

Ferric CitrateDRUG

Auryxia® 210 mg ferric iron tablets equivalent to 1 g of FC will be supplied as 200 tablets in 400cc high-density polyethylene bottles.

PlaceboDRUG

Placebo to match Ferric Citrate tablets

Eligibility

Sex: ALLMin age: 6 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

University of California, Los Angeles

Los Angeles, California, United States

Outcomes

Primary Outcomes

iFGF23 levels

Compared to placebo, active treatment with FC will lower iFGF23 levels

Time frame: 12 months

Safety of Ferric Citrate

Comparing proportion of subjects with AE and SAE between arms

Time frame: 12 months

Tolerability of Ferric Citrate

Compared with placebo, active treatment will be tolerable

Time frame: 12 months

Secondary Outcomes

Effects on Transferrin Saturation (TSAT)

Compared with placebo, active treatment with FC will be associated with larger increase in hemoglobin, higher TSAT and higher Ferritin from baseline

Time frame: 12 months

Effects on PTH and 1,25 D

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

Time frame: 12 months

Central Contacts

JENNY BROOK, MS

CONTACT

310-7943144 jbrook@mednet.ucla.edu

Barbara Gales, RN

CONTACT

310-206-0799 bgales@mednet.ucla.edu

Data from ClinicalTrials.gov

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