Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (ASCEND-P)

Study Overview
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Brief Summary
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This is an international, multicenter trial, evaluating pharmacokinetics (PK) (4 weeks), safety (52 weeks), and hemoglobin (Hgb) response (52 weeks) to daprodustat in children and adolescent participants with anemia associated with chronic kidney disease (CKD) incorporating 2 independent sub-trials (Non dialysis [ND] and Dialysis [D]). This study will enroll participants with anemia associated with CKD, in 2 distinct sub-populations differing only by their CKD stage and dialysis requirement (ND: CKD stage 3 to 5 not yet receiving dialysis and D: CKD stage 5d undergoing peritoneal dialysis [PD] or hemodialysis [HD]). The maximum duration of the study will be approximately 60 weeks, including Screening period (up to 4 weeks), treatment period (52 weeks), and follow-up period (4 weeks). Outcome measures are identical for the ND and D sub-trials, but will be separately assessed in each sub- trials, overall and within each age subgroups (12 to less than [<] 18 years, 6 to <12 years, 2 to <6 years, and 3 months to <2 years). Except for PK and dose change, which is within each age group only.

Official Title
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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

Conditions
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Anaemia

Intervention / Treatment
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* Drug: Daprodustat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 3 months to less than (<)18 years of age. Anemia associated with CKD stage 3, 4, 5 (not on dialysis) or who have dialysis-dependent CKD, defined as Hgb 7.0 to 11.0 g/dL (if not using erythropoiesis stimulating agents [ESAs]) or Hgb 9.5 to 12.0 g/dL if using ESAs. Written informed consent or assent as appropriate. Exclusion Criteria: Kidney transplant recipient with a functioning allograft. Scheduled for elective kidney transplantation within 3 months. Transferrin saturation (TSAT) < 20 percent (%), or Ferritin <25 nanogram (ng)/milliliter (mL). History of bone marrow aplasia or pure red cell aplasia. Active hemolysis. Other causes of anemia. Active gastrointestinal bleeding within the last 4 weeks. Active or previous malignancy within the last 2 years. Acute or chronic infection requiring antimicrobial therapy. History of significant thrombotic or thromboembolic events within the last 8 weeks. Heart failure (HF) New York Heart Association (NYHA) Class IV Uncontrolled hypertension. Alanine aminotransferase (ALT) >2× upper limit of normal (ULN), bilirubin >1.5× ULN (unless bilirubin is fractionated and direct bilirubin <35%), and cirrhosis or current unstable liver or biliary disease.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label single arm trial, where all participants are on active treatment with daprodustat.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daprodustat<br>All participants will receive daprodustat for up to 52 weeks. | Drug: Daprodustat<br>* Daprodustat will be administered up to Week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | All AEs and SAEs will be collected. | Up to 56 weeks | 
| Number of participants with adverse event of special interests (AESIs) | All AESI will be collected. | Up to 56 weeks | 
| Number of participants with AEs leading to study intervention discontinuation | All AEs leading to study intervention discontinuation will be collected. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with change from baseline in laboratory safety parameters | Number of participants with abnormal laboratory safety parameters will be assessed. | Baseline (Day 1) and up to Week 56 | 
| Mean change from baseline in blood pressure (BP) | Blood pressure readings in millimeters of mercury (mmHg) will be collected. | Baseline (Day 1) and up to Week 56 | 
| Mean change from baseline in heart rate (HR) | Heart rate readings in beats per minutes (bpm) will be collected. | Baseline (Day 1) and up to Week 56 | 
| Mean change from baseline in weight | Weight readings in kilogram (kg) will be collected. | Baseline (Day 1) and up to Week 56 | 
| Mean change from baseline in height | Height readings in centimeters (cm) will be collected. | Baseline (Day 1) and up to Week 56 | 
| Mean Hgb value | Blood samples will be collected from all participants for measurement of Hgb (grams per deciliter [g/dL]) values. | Up to Week 56 | 
| Mean change from baseline in Hgb values | Blood samples will be collected from all participants for measurement of Hgb (g/dL) values. | Baseline (Day 1) and up to Week 56 | 
| Number of participants with Hgb values above, below and within the target range (10 to 12 g/dL) | Number of participants with Hgb values above, below, and within the target range (10 to 12g/dL) will be assessed. | Up to week 56 | 
| Mean daprodustat dose | Mean values of daprodustat will be calculated and reported. | Up to Week 56 | 
| Number of participants with 0 to 10, or greater than [>] 10 dose adjustments | Number of participants with 0 to 10, or >10 dose adjustments form the starting dose of dapurodustat will be assessed. | Up to Week 56 | 
| Number of participants assigned to each dose level at each visit | Number of participants assigned to each dose level of dapurodustat will be assessed | Up to Week 56 | 
| Maximum plasma concentration (Cmax) of daprodustat and its metabolites | Blood samples will be collected for the plasma concentrations of daprodustat from which PK parameters will be determined. | Up to Week 4 | 
| Area under the curve (AUC) at steady state of daprodustat and its metabolites | Blood samples will be collected for the plasma concentrations of daprodustat from which PK parameters will be determined. | Up to Week 4 | 
| Plasma concentrations of daprodustat metabolites at pre-dose trough (Ctrough) | Blood samples will be collected for the plasma concentrations of daprodustat metabolites from which PK parameters will be determined. | Up to Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Daprodustat, ASCEND-P, Anemia, Chronic kidney disease, Erythropoiesis stimulating agent, Dialysis, Non-dialysis, 214066, 212914