Anemia Chronic Kidney Disease
Conditions
Interventions
All participants will receive oral daprodustat for a total of 52 weeks and will
be followed for an additional 4 weeks after completing treatment. The lowest
dose level defined (0.125 mg once daily [
Sponsors
GSK Research & Development Limited
Eligibility
Age
No minimum to 17 Years
Inclusion criteria
Inclusion criteria: 1. Participant must be 3 months to <18 years of age. Note: Infants born prematurely (under 32 weeks of gestation) should have a chronological age of at least 6 months. 2. Participants who have anemia associated with CKD as follows: Non-Dialysis sub-trial: CKD stage 3, 4, 5 (not on dialysis) based on eGFR using the bedside Schwartz equation <60 mL/min/1.73m2 Dialysis sub-trial: Prevalent dialysis patients (Stage 5d CKD) defined as those in receipt of maintenance dialysis of <=30 days duration AND if not using ESAs, Hgb 7.0 to 11.0 g/dL OR If using ESAs, Hgb 9.5 to 12 g/dL 3. Weight restrictions apply to participants for each age group. This takes into account: - In the 3 younger age groups (<12 years), the number of TfOS they may receive in the trial to ensure dosing is well below excipient limits. The weight used for excipient limit calculation in each age group is based on WHO median weights in girls (lighter than boys) minus 2 SD for the youngest child in each age group (i.e., 6 years, 2 years and 3 months). - The minimum weight used in the PBPK model assumptions, see Section 4.3. - Relevant for the youngest patients (3 months), the minimum weight also takes into account the amount of blood required for study time points relative to percentage of blood volume in order to comply with guidance for clinical trials in children, see Section 8.4.1. Participants must weight or exceed the minimum weight required for study entry tabulated for their age group, as indicated in the second column of table 12 of the protocol. 4. A female participant is eligible to participate if she is either: • premenarcheal, or • not pregnant as confirmed by a negative human chorionic gonadotrophin (hCG) test if of reproductive potential. Testing requires serum hCG if eGFR<=15 mL/min/1.73m2. Otherwise, a urine hCG test is acceptable. Females of childbearing potential (FOCBP) must commit to consistent and correct use of a highly effective method of contraception for the duration of the trial and 30 days after the last dose of daprodustat. A pregnancy test is required for FOCBP. This test will be performed at the initial Screening and at each scheduled visit whilst in the study including the follow-up visit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy. Note: If the childbearing potential changes after start of the study (e.g., a premenarcheal female participant experiences menarche) or the risk of pregnancy changes (e.g., a female participant who is not heterosexually active becomes active), the participant must discuss this with the investigator, who should determine if a female participant must begin a highly effective method of contraception. If reproductive status is questionable, additional evaluation should be considered. 5. The investigator, or a person designated by the investigator, will obtain written informed consent from each study participant's legal guardian and the participant's assent, when applicable, before any study specific activity is performed (unless a waiver of informed consent has been granted by an IRB/IEC). All legal guardians should be fully informed, and participants should be informed
Exclusion criteria
Exclusion criteria: 1. Kidney transplant recipient with a functioning allograft 2. Scheduled for elective kidney transplantation within 3 months. 3. Iron deficiency, defined as: - Transferrin saturation (TSAT) 480 msec, or • QT interval corrected for heart rate (QTc) >500 msec in participants with bundle branch block. 14. Liver abnormality/disease: • Alanine aminotransferase (ALT) >2× upper limit of normal (ULN). • Bilirubin >1.5× ULN (isolated bilirubin >1.5× ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). • Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones and chronic hepatitis B or C) is acceptable if the participant otherwise meets entry criteria. 15. Participants who have previously received treatment with any HIF-PHI, including daprodustat within the last 30 days. 16. Participants who have previously failed to respond to treatment with daprodustat or any other HIF-PHI. 17. Participants, who have received within the last 7 days, or anticipate receiving during the study, strong inhibitors of CYP2C8 (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin). 18. Other investigational product/clinical study: Participants who have received treatment with an investigational agent (bi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs leading to study intervention discontinuation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes from baseline in laboratory safety parameters, blood pressure (BP), heart rate (HR),height and weight at each time point. At each study time point: • Hgb value. • Hgb change from baseline. • Hgb above, below and within the target range (10 to 12 g/dL). At each study time point: • Daprodustat dose. • Daprodustat dose change from starting dose. During the course of the study: • Number of dose changes. PK parameters: maximum plasma concentration (Cmax) and Area Under the Curve (AUC) at steady state. Plasma concentrations of each daprodustat metabolite at pre-dose (trough) between Week 2 to Week 4, and corresponding Cmax if data permit. | — |
Countries
Netherlands
Outcome results
None listed