Clinical trial NCT04741646: Ferric Citrate and Chronic Kidney Disease in Children
Official title: Phosphate Binder Therapy and Chronic Kidney Disease in Children
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Diseases
Keywords: Pediatric
CKD
Phosphate Binder
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-02-05
Enrollment: 160
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: iFGF23 levels
timeFrame: 12 months
measure: Safety of Ferric Citrate
timeFrame: 12 months
measure: Tolerability of Ferric Citrate
timeFrame: 12 months
Secondary outcomes:
measure: Effects on Transferrin Saturation (TSAT)
timeFrame: 12 months
measure: Effects on PTH and 1,25 D
timeFrame: 12 months
Other outcomes:
measure: GFR
timeFrame: 12 months
measure: Osteoid thickness
timeFrame: 12 months
measure: Effects on bone expression
timeFrame: 12 months
measure: Effects on phosphate
timeFrame: 12 months
measure: Effects on calcium
timeFrame: 12 months
measure: Effects on 1,25 (OH) D levels
timeFrame: 12 months
measure: Effects on bone biomarkers
timeFrame: 12 months
measure: Effects on Klotho
timeFrame: 12 months
measure: Effects on cFGF23
timeFrame: 12 months
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana U
state: Indiana
city: Kansas City
country: United States
facility: Children's Mercy Hospital, Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington U
state: Missouri
city: New York
country: United States
facility: Cohen's Childrens
state: New York
city: The Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Durham
country: United States
facility: Duke
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's
state: Ohio
city: Portland
country: United States
facility: OHSU
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center, Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: UTH
state: Texas
city: Vancouver
country: Canada
facility: BC Children's Hospital Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: SickKids
state: Ontario
Study officials:
affiliation: University of California, Los Angeles
name: Isidro B Salusky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hanudel MR, Laster ML, Portale AA, Dokras A, Quigley RP, Guzman GAL, Zaritsky JJ, Hayde NA, Kaskel FJ, Mitsnefes MM, Ramirez JA, Imani PD, Srivaths PR, Kogon AJ, Denburg MR, Blydt-Hansen TD, Reyes LZ, Greenbaum LA, Weidemann DK, Warady BA, Elashoff DA, Mendley SR, Isakova T, Salusky IB. A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial. Pediatr Nephrol. 2022 Nov;37(11):2547-2557. doi: 10.1007/s00467-022-05492-7. Epub 2022 Mar 2.