An Integrated Pharmacokinetic and Safety Open-label Basket Trial of Daprodustat for the Treatment of Anemia Associated with Chronic Kidney Disease in Male and Female Children and Adolescents Aged 3 Months to Under 18 Years Requiring or Not Requiring Dialysis.

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 to the fullest extent possible, about the study in language and terms
they are able to understand.

6. The participant capable of providing signed and dated written assent, signs
and dates a written assent form (age-appropriate) and the parent/guardian signs
and dates a written informed consent form (ICF) for study participation prior
to the initiation of any study-related activities. The informed consent is
described in Section 10.1.3.

7. A legal guardian or primary caregiver must be available to help the study
site personnel ensure follow-up; support the participant to attended assessment
days according to the SoA in Section 1.3 (e.g., able to comply with scheduled
visits, study procedures, and accurately dispense study intervention as
directed).

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) < 20%, or
- Ferritin <25 ng/mL.
4. Aplasias: History of bone marrow aplasia or pure red cell aplasia.
5. Active hemolysis.
6. Other causes of anemia: e.g., untreated vitamin B12 deficiency, untreated
folate deficiency, thalassemia major, sickle cell disease or myelodysplastic
syndrome.
Note: Sickle cell trait is acceptable if the participant otherwise meets entry
criteria.
7. GI bleeding: Evidence of actively bleeding gastric, duodenal or esophageal
ulcer disease or clinically significant GI bleeding within the last 4 weeks.

8. History of malignancy within the last 2 years or currently receiving
treatment for cancer, or renal lesions, for which, in the opinion of the
investigator, malignancy cannot be excluded.
Note: The only exception is localized squamous cell or basal cell carcinoma of
the skin that has been definitively treated within the last 4 weeks.
9. History of significant thrombotic or thromboembolic events (e.g., deep
venous thrombosis, pulmonary embolism, stroke, myocardial infarction [MI])
within the last 8 weeks.

10. History of significant thrombotic or thromboembolic events (e.g., deep
venous thrombosis, pulmonary embolism, stroke, myocardial infarction [MI])
within the last 8 weeks.
11. Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart
Association (NYHA) functional classification system.
12. Current uncontrolled hypertension as determined by the investigator.
13. 12-lead electrocardiogram (ECG) finding (at Screening):
• An abnormal ECG finding from the 12-lead ECG conducted at Screening if
considered to be clinically significant and would impact the participant*s
participation during the study based on the evaluation of the investigator and
a pediatric cardiologist.
• QT interval corrected using Fridericia*s formula (QTcF) > 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 (biologic or non-biologic)
within the past 30 days or 5 drug half-lives whichever is longer, with the
exception of treatments or vaccines for SARS-CoV-2 with provisional or
emergency approval. The term *investigational* applies to any drug not approved
for sale in the country in which it is being used or investigational
formulations of marketed products.
19. Participants who are currently participating in any other clinical study of
an investigational medicinal product (IMP).
20. Females ONLY: Participant is pregnant, breastfeeding or is of reproductive
potential and does not agree to one of the contraceptive options listed in the
List of Highly Effective Methods for Avoiding Pregnancy in Section 10.4.
21. Participants with any history of hypersensitivity to daprodustat or its
excipients, or to any other HIF-PHI.
22. Any other condition, clinical or laboratory abnormality, or examination
finding that the investigator considers would put the participant at
unacceptable risk, which may affect study compliance or prevent understanding
of the aims or investigational procedures or possible consequences of the
study.