Ferric Citrate and Chronic Kidney Disease in Children

Официальное название

Phosphate Binder Therapy and Chronic Kidney Disease in Children

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат Ferric 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.
• Препарат Placebo
  Placebo to match Ferric Citrate tablets

Первичные конечные точки

• iFGF23 levels [Срок оценки: 12 months]
• Safety of Ferric Citrate [Срок оценки: 12 months]
• Tolerability of Ferric Citrate [Срок оценки: 12 months]

Вторичные конечные точки (2)

• Effects on Transferrin Saturation (TSAT) [Срок оценки: 12 months]
• Effects on PTH and 1,25 D [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Ages 6 to 18 years (inclusive);
• 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
• Serum phosphate <=5.9 mg/dl;
• Serum ferritin <500 ng/ml and TSAT <50%;
• 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;
• Able to swallow tablets;
• Able to eat at least two meals a day;
• In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.

Критерии исключения

• Patients currently treated with phosphate binders.
• History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
• Current intestinal malabsorption, documented in the medical record; disease, inflammatory bowel syndrome, and/or Crohn's Disease.
• Anticipated initiation of dialysis or kidney transplantation within 6 months
• Current or planned future systemic immunosuppressive therapy
• Prior solid organ transplantation
• Receipt of bone marrow transplant within two years of screening
• Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
• Patients participating in other interventional study (observational study participation permitted)
• Poor adherence to medical treatments in the opinion of the investigator
• Cystinosis
• Fanconi syndrome
• Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 18 центров

• University of California, Los Angeles — Los Angeles
• Children's Hospital of Orange County — Orange
• University of California, San Francisco — San Francisco
• Arnold Palmer Hospital for Children — Orlando
• Emory University — Atlanta
• Indiana U — Indianapolis
• Children's Mercy Hospital, Kansas City — Kansas City
• Washington U — St Louis
• … и ещё 10 центров

Канада · 2 центра

• BC Children's Hospital Research Institute — Vancouver
• SickKids — Toronto

Публикации

• 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 Kidn PMID 35237863

Идентификаторы

NCT: NCT04741646 · U01DK122013 · 1U01DK122013 · 22-001133

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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