Roxadustat is a licensed medicine to treat anemia in adults with chronic kidney disease (CKD). Anemia is a low level of red blood cells. Current treatment for anemia is to have injections of medicines called erythropoietin stimulating agents (also known as ESAs) to help the bone marrow make more red blood cells. These are often given together with iron. This treatment is also available to children and teenagers with CKD. However, there are some safety concerns with ESAs. Also, as roxadustat is taken orally, this may be another option for treating anemia in children and teenagers with CKD. In this study, children and teenagers with CKD and anemia will take roxadustat for up to 52 weeks to treat their anemia. The main aim of the study is to learn how roxadustat affects anemia in children and teenagers with CKD. This is an open-label study which means the children and teenagers in the study and the clinic staff know they will be taking roxadustat. In this study, the children and teenagers with CKD who need treatment for anemia can take part. Those currently being treated with an ESA will be switched to roxadustat. Those who have not been treated with an ESA can start on roxadustat straight away. All children and teenagers in the study will take roxadustat 3 times a week for up to 52 weeks (1 year). They will start on a fixed dose of roxadustat for 4 weeks. Blood samples will be taken regularly to check hemoglobin levels. The roxadustat dose may be changed if the blood levels of hemoglobin are too high, too low, or change too quickly. After 4 weeks the dose may be changed, if needed, to keep blood levels of hemoglobin in the blood to just below the normal range. Firstly, teenagers will take roxadustat. 10 teenagers will take their fixed dose of roxadustat for 4 weeks. They will give blood samples to help the researchers work out the most suitable dose for the rest of the teenagers in the study. When the rest of the teenagers start taking roxadustat at the most suitable dose for teenagers, 10 children will take roxadustat for 4 weeks. These 10 children will give blood samples to help the researchers work out the most suitable dose for the rest of the children in the study. Then, the rest of the children will take roxadustat at the most suitable dose for children. There will be many clinic visits during the study. Overnight hospital stays are not expected. There will be 1 visit every 2 weeks for the first 4 weeks of taking roxadustat, then every 4 weeks until the end of treatment. Finally there is 1 visit 4 weeks after treatment has finished. During most visits, the children and teenagers will have their vital signs checked (blood pressure, body temperature and heart rate). Fluid status (how much water is in the body) will also be checked for those who need dialysis. The children and teenagers will also have blood tests and the study doctors will check for any medical problems. The children and teenagers will have a medical examination before their first dose of roxadustat and again at about 24-week (6-month) and 52-week (13-month) visits. They will have an electrocardiogram (ECG) before their first dose of roxadustat and again at the 12-week, 24-week, 36-week, and 52-week visit. They will also have urine tests at the 4-week, 24-week and 52-week visits. At the 52-week visit, the children and teenagers will also have blood tests for hemoglobin and iron levels. The study doctors will also check for any medical problems.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Oral
Site BE32002
Brussels, Belgium
RECRUITINGSite BE32001
Edegem, Belgium
RECRUITINGSite BE32004
Ghent, Belgium
RECRUITINGSite BE32003
Leuven, Belgium
Change from baseline in Hb level to the average Hb level over treatment weeks 20 to 24
Mean change in Hb level between baseline and average Hb level over treatment weeks 20 to 24.
Time frame: Baseline and weeks 20 to 24
Pharmacokinetics (PK) of roxadustat in plasma: Maximum concentration (Cmax)
Cmax will be recorded from the PK plasma samples collected.
Time frame: Up to week 8
PK of roxadustat in plasma: Area under the plasma-concentration time curve (AUC)
AUC will be recorded from the PK plasma samples collected.
Time frame: Up to week 8
PK of roxadustat in plasma: Apparent total clearance (CL/F)
CL/F will be recorded from the PK plasma samples collected.
Time frame: Up to week 8
PK of roxadustat in plasma: Time of the maximum concentration (Tmax)
Tmax will be recorded from the PK plasma samples collected.
Time frame: Up to week 8
Hb levels at all timepoints
Hb levels at all timepoints will be recorded.
Time frame: Up to week 56
Dose titration history at all timepoints
Dose titration history at all timepoints will be recorded.
Time frame: Up to week 52
Number of participants with treatment-emergent adverse events (TEAEs)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of roxadustat, whether or not considered related to roxadustat. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of roxadustat. This includes events related to the comparator and events related to the (study) procedures. A TEAE is defined as an AE observed after starting administration of roxadustat through 28 days after the last dose of roxadustat.
Time frame: From first dose of study drug and up to week 56
Number of participants with treatment-emergent cardiovascular AEs
Treatment-emergent cardiovascular AEs will be recorded.
Time frame: From first dose of study drug and up to week 56
Number of participants with treatment-emergent thrombotic AEs
Treatment-emergent thrombotic AEs will be recorded.
Time frame: From first dose of study drug and up to week 56
Number of participants with laboratory value abnormalities and/or AEs
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to week 52
Number of participants with vital sign abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to week 52
Change from baseline in growth parameter value: Height
Height will be recorded at all timepoints.
Time frame: Baseline and up to week 52
Change from baseline in growth parameter value: Weight
Weight will be recorded at all timepoints.
Time frame: Baseline and up to week 52
Number of participants with physical examinations abnormalities and/or AEs
Number of participants with potentially clinically significant physical examination abnormalities.
Time frame: Up to week 52
Percentage of participants with Hb response
Response is defined as a participant achieving 2 consecutive Hb values within 1 g/dL of baseline (ESA-treated participants only) or achieving the target range of 10.0 to 12.0 g/dL at the end of the 24-week treatment evaluation period (i.e., weeks 20 to 24) without having received rescue therapy within 6 weeks prior to or during this 4-week evaluation period.
Time frame: Up to Week 24
Mean monthly intravenous (IV) iron use
Summaries of monthly IV iron usage (number of administrations) will be recorded.
Time frame: Up to week 52
Mean Monthly total IV iron dosage
Summaries of monthly IV iron usage (total dosage) will be recorded.
Time frame: Up to week 52
Percentage of participants using IV iron
Percentage of participants using IV iron by study period will be recorded.
Time frame: Up to week 52
Percentage of participants using oral iron
Percentage of participants using oral iron by study period will be recorded.
Time frame: Up to week 52
Percentage of participants using rescue therapy
Percentage of participants using rescue therapy by study period will be recorded.
Time frame: Up to week 52
Palatability questionnaire
The palatability questionnaire will assess taste and ability to swallow the medication using a 5 point Likert scale: for taste from 0 (Really bad) to 4 (Really good); for ability to swallow from 0 (Really Difficult) to 4 (Really Easy). The number of participants recorded for each response category will be provided.
Time frame: Up to week 52
Change from baseline in Pediatric Quality of Life (PedsQL) Inventory Score
PedsQL Inventory Scale comprises of 23 items (except for ages 2-4 which has only 21 items, 3 of which are only answered if the child attends school or daycare) in 4 domains: physical functioning, emotional functioning, social functioning and school functioning. A Likert scale from 0 (Never) to 4 (Almost always) will be used to record response. Higher scores indicate better quality of life.
Time frame: Baseline and up to week 52
Change from baseline in PedsQL Multidimensional Fatigue Scale questionnaire QoL Score
PedsQL Multidimensional Fatigue Scale comprises of 18 items in 3 domains: general fatigue, sleep/rest fatigue and cognitive fatigue. A Likert scale from 0 (Never) to 4 (Almost always) will be used to record response. Higher scores indicate better quality of life.
Time frame: Baseline and up to week 52
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