Clinical trial NCT04523727: Study to Evaluate the Safety and Tolerability of Ferric Citrate in Children With Hyperphosphatemia Related to Chronic Kidney Disease
Official title: A 36-week, Single-Arm, Open-label Study to Evaluate the Safety and Tolerability of Ferric Citrate in Children With Hyperphosphatemia Related to Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hyperphosphatemia Related to Chronic Kidney Disease
Keywords: hyperphosphatemia
chronic kidney disease
CKD
ferric citrate
pediatric
dialysis
Lead sponsor: Keryx Biopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-08-24
Enrollment: 45
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will be conducted to assess the safety and tolerability of ferric citrate in pediatric participants with hyperphosphatemia related to chronic kidney disease (CKD).


Eligibility criteria: Inclusion Criteria:

* Age 6 years to \<17 years at Screening.
* Weight ≥ 20 kilograms (kg) (dry weight for dialysis participants) at Screening.
* Chronic kidney disease (CKD) requiring chronic dialysis (i.e., hemodialysis or peritoneal dialysis), or CKD not on dialysis with an estimated glomerular filtration rate (eGFR) \<30 milliliters per minute (mL/min)/1.73 meters squared (m\^2) at Screening.
* Documented history of CKD-related hyperphosphatemia for at least 3 months prior to the screening visit.
* If participant is or is not on phosphate binder(s) at Visit 1, serum phosphorus must be:

  * 6 to \<13 years: \>5.8 milligrams per deciliter (mg/dL).
  * 13 to \<17 years: \>4.5 mg/dL.
* If participant is on phosphate binder(s) at Visit 1, and serum phosphorus is not greater than the above stated age-limit criteria, approximately 1 to 4-weeks of washout period is required and at Visit 1a or Visit 1b, serum phosphorus must be greater than the age above stated age-limit criteria.
* Transferrin saturation (TSAT) \<50%.
* Serum ferritin of \<650 nanograms per milliliter (ng/mL).
* Parent/legal guardian must be willing and able to give written informed consent, and child (participant) willing and able to give age-appropriate assent according to local regulatory requirements.
* Female participants of childbearing potential, defined as post menarche and not surgically sterile, must have a negative serum pregnancy test.
* Dialysis adequacy stable on current mode of dialysis prior to screening and agree to maintain dialysis prescription for the duration of the pharmacodynamic assessment period unless changes are needed for safety. A minimum dialysis adequacy (dialysis clearance of urea-dialysis time/volume of distribution of urea \[Kt/V\]), defined by the following:

  1. Hemodialysis adequacy: single-pool Kt/V ≥1.2 for at least 1 hemodialysis session within 2 months.
  2. Peritoneal dialysis: At least 1Kt/V reading ≥1.8 within 4 months.

Exclusion Criteria:

* Active significant GI disorder, including overt GI bleeding or active inflammatory bowel disease.
* Liver transaminases (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) \>3× the upper limit of normal at Screening.
* Unable to swallow pills, if participant requires tube feeding, ferric citrate must be taken orally and not administered via feeding tube.
* Non-renal cause of hyperphosphatemia.
* Active drug or alcohol dependence or abuse (excluding tobacco use or medicinal marijuana) within the 12 months prior to Screening or evidence of such abuse (in the opinion of the Investigator).
* Malignancy, except for participants who have been disease-free for at least 2 years after curative therapy.
* Participants with a functioning organ transplant.
* A known allergy or intolerance to ferric citrate or any of its constituents.
* Female participants who do not agree to remain abstinent or assent to use a combination of 2 of the following highly effective birth control methods for at least 28 days before the first dose, during the study (including during dose interruptions), and for at least 30 days after the last dose:

  * Barrier method of contraception: condoms (female or male) with or without a spermicidal agent, diaphragm, or cervical cap with spermicide.
  * Intrauterine device (IUD).
  * Hormone-based contraceptives which are associated with inhibition of ovulation.
* Females who are pregnant or breast-feeding other children. Participants who are being breastfed are eligible to participate in this study.
* Any other medical condition that, in the opinion of the Investigator, renders the participant unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the participant.
* The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study.
* Receipt of any investigational drug within 4 weeks before Screening.
* History of hemochromatosis or iron overload syndrome (e.g, hereditary sideroblastic anemia, thalassemia).

Primary outcomes:
measure: Number of participants with serious and non-serious treatment-emergent adverse events (TEAEs) including gastrointestinal (GI) AEs of special interest
timeFrame: up to Week 40
measure: Number of participants with clinically significant laboratory abnormalities or changes in laboratory results
timeFrame: up to Week 40
measure: Number of participants with TEAEs leading to the discontinuation of ferric citrate
timeFrame: up to Week 40
Secondary outcomes:
measure: Change from baseline in serum phosphorus to Week 12/early termination (ET)
timeFrame: Baseline; up to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) - Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF) - Department of Nephrology
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Kansas City
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Akebia Therapeutics Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: