E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia associated with chronic kidney disease (CKD) |
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E.1.1.1 | Medical condition in easily understood language |
Anemia associated with chronic kidney disease (CKD) |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary (Safety): Describe the safety of daprodustat, overall (all ages) and in each age group |
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E.2.2 | Secondary objectives of the trial |
Secondary Safety: Describe changes in other parameters relevant to safety, overall and in each age group.
Secondary Efficacy: - Describe the effect of daprodustat on Hgb, overall and in each age group (and additionally overall in all ages by ESA use [yes/no] at study enrollment). - Describe the change in required dose over time, in each age group.
Secondary Pharmacokinetic: - Characterize the PK of daprodustat in each age group. - Describe the systemic exposure to daprodustat metabolites, M2, M3, M4, M5, M6 and M13 in each age group. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 described in the protocol. Weight: 3. Weight restrictions apply to participants for each age group as described in 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. 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). 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.
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E.4 | Principal 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) < 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: In the case of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated, the exclusion timelines is within the last 4 weeks. 9. Unresolved acute or active chronic infection requiring antimicrobial therapy . 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 as described in the protocol. 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. 19. Participants who are currently participating in any other clinical study of an investigational medicinal product (IMP). 20. Participants with any history of hypersensitivity to daprodustat or its excipients, or to any other HIF-PHI. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary (Safety): Incidence of AEs, Serious Adverse Events (SAEs), AESIs, and AEs leading to study intervention discontinuation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AE/SAE assessment: From Screening (-4 weeks to Day 1) to Follow-up (week 56) |
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E.5.2 | Secondary end point(s) |
Secondary Safety: Changes from baseline in laboratory safety parameters, blood pressure (BP), heart rate (HR), height and weight at each time point.
Secondary Efficacy: 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.
Secondary Pharmacokinetic: • 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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Vital signs (BP, HR), Height, weight: From Screening (-4 weeks to Day 1) to Follow-up (week 56) Hgb (full blood count): From Screening (-4 weeks to Day 1) to Follow-up (week 56) PK Sampling (Optional unless in the Integrated PK Phase): Day 1, Week 2, Week 4 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Australia |
Canada |
Japan |
Korea, Republic of |
United States |
Turkey |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study (EOS) Overall is defined as the date of the last visit of the last participant in the study of the last sub-trial (ND or D) to finish. As these sub-trial populations (ND/D) are handled separately within the master basket trial protocol, their last participant visit will differ, particularly if recruitment rate varies between the 2 sub-trial populations. Therefore, an EOS ND and an EOS D is also defined. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |