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.
Brief Title
Ferric Citrate and Chronic Kidney Disease in Children
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
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
Central Contacts
Central Contact Role
Contact
Central Contact Phone
310-7943144
Central Contact Email
jbrook@mednet.ucla.edu
Central Contact Role
Contact
Central Contact Phone
310-206-0799
Central Contact Email
bgales@mednet.ucla.edu
Completion Date
Completion Date Type
Estimated
Conditions
Chronic Kidney Diseases
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
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
Inclusion 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.
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.
Gender
All
Gender Based
false
Keywords
Pediatric
CKD
Phosphate Binder
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
18 Years
Minimum Age
6 Years
NCT Id
NCT04741646
Org Class
Other
Org Full Name
University of California, Los Angeles
Org Study Id
U01DK122013
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Phosphate Binder Therapy and Chronic Kidney Disease in Children
Primary Outcomes
Outcome Description
Compared to placebo, active treatment with FC will lower iFGF23 levels
Outcome Measure
iFGF23 levels
Outcome Time Frame
12 months
Outcome Description
Comparing proportion of subjects with AE and SAE between arms
Outcome Measure
Safety of Ferric Citrate
Outcome Time Frame
12 months
Outcome Description
Compared with placebo, active treatment will be tolerable
Outcome Measure
Tolerability of Ferric Citrate
Outcome Time Frame
12 months
Secondary Ids
Secondary Id
1U01DK122013
Secondary Id
22-001133
Secondary Outcomes
Outcome Description
Compared with placebo, active treatment with FC will be associated with larger increase in hemoglobin, higher TSAT and higher Ferritin from baseline
Outcome Time Frame
12 months
Outcome Measure
Effects on Transferrin Saturation (TSAT)
Outcome Description
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
Outcome Time Frame
12 months
Outcome Measure
Effects on PTH and 1,25 D
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
18
Minimum Age Number (converted to Years and rounded down)
6
Investigators
Investigator Type
Principal Investigator
Investigator Name
Frederick Kaskel
Investigator Email
FKASKEL@montefiore.org
Investigator Phone
718-655-1120