Ferric Citrate and Chronic Kidney Disease in Children (FIT4KID)

University of California, Los Angeles (UCLA)

Status and phase: Enrolling; Phase 2

Conditions: Chronic Kidney Diseases

Treatments: Drug: Ferric Citrate; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04741646

U01DK122013 (U.S. NIH Grant/Contract)

22-001133 (Other Identifier)

1U01DK122013 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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

Enrollment: 160 estimated patients

Sex: All

Ages: 6 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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160 participants in 2 patient groups, including a placebo group

Treatment Arm

Experimental group

Description:

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.

Treatment:

Drug: Ferric Citrate

Control Arm

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo