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

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

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.

Study Overview

• Status: Completed
• Conditions: Anaemia
• Intervention / Treatment: Drug: Daprodustat

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 466-8650
    • GSK Investigational Site
  • Saitama, Japan, 330-8777
    • GSK Investigational Site
  • Tokyo, Japan, 162-8666
    • GSK Investigational Site
• South Korea
  • Yangsan, South Korea, 50612
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daprodustat; All participants will receive daprodustat for up to 52 weeks.	Drug: Daprodustat; Daprodustat will be administered up to Week 52.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other situations as per medical and scientific judgement of the Investigator.	Up to 56 weeks
Number of Participants With Adverse Event of Special Interests (AESIs)	AESIs are AEs of scientific interest specific to the drug class as per investigator assessment. AESI included: Death, Myocardial Infarction (MI), stroke, Heart Failure (HF), thromboembolic events, thrombosis of vascular access, Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis, New diagnosis of hypertension or worsening of existing hypertension, Cancer related mortality and tumor progression and recurrence, Esophageal and gastric erosions. Number of participants with any AESIs have been presented.	Up to 56 weeks
Number of Participants With AEs Leading to Study Intervention Discontinuation	All AEs leading to study intervention discontinuation were collected. Number of participants with any AEs leading to study intervention discontinuation have been presented	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes	Blood samples were collected to analyze the hematology parameter: Reticulocytes/Erythrocytes. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: Erythrocytes. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelet Count	Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelet count. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Clinical Chemistry Parameters: Calcium, Potassium, Sodium, Blood Urea Nitrogen (BUN)	Blood samples were collected to analyze the clinical chemistry parameters: Calcium, Potassium, Sodium and BUN. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Clinical Chemistry Parameter: Creatinine	Blood samples were collected to analyze the clinical chemistry parameter: Creatinine. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)	Blood samples were collected to analyze the clinical chemistry parameters: ALT, ALP and AST. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52
Change From Baseline in Clinical Chemistry Parameters: Bilirubin and Direct Bilirubin	Blood samples were collected to analyze the clinical chemistry parameters: Bilirubin and Direct Bilirubin. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52
Change From Baseline in Clinical Chemistry Parameter: Protein	Blood samples were collected to analyze the clinical chemistry parameter: Protein. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52
Change From Baseline in Clinical Chemistry Parameter: Ferritin	Blood samples were collected to analyze the clinical chemistry parameter: Ferritin. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Clinical Chemistry Parameter: Transferrin Saturation	Blood samples were collected to analyze the clinical chemistry parameter: Transferrin saturation. Transferrin saturation is measured as a percentage, it is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Clinical Chemistry Parameter: Estimated Glomerular Filtration Rate	Blood samples were collected to analyze the clinical chemistry parameter: Estimated Glomerular Filtration Rate. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio	Blood samples were collected to analyze the hematology parameter: Prothrombin International Normalized Ratio. It is used to assess the clotting ability of blood. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 4, 8, 12, 24, 32, 36, 40, 48, and 52
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Systolic and diastolic blood pressure (BP) were assessed using an appropriate size cuff preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Heart Rate (HR)	Heart rate (HR) were assessed using an appropriate size cuff preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Weight	Weight readings in kilogram (kg) were collected. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Height	Height readings in centimeters (cm) were collected. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Absolute Values of Hemoglobin (Hgb)	Blood samples were collected from all participants for measurement of Hgb values in grams per deciliter (g/dL). Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Hgb results of participants with intercurrent events were excluded from the summary.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Hemoglobin (Hgb)	Blood samples were collected from all participants for measurement of Hgb values in g/dL. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline. Hgb results of participants with intercurrent events were excluded from the summary.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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 12 g/dL) were assessed. Baseline assessment was defined as the last non-missing value prior to the start date and time of the study drug (Day 1). Hgb results of participants with intercurrent events were excluded from the summary.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change in Daprodustat Dose From Starting Dose at Each Study Time Point	Daprodustat dose was adjusted, if required, one step at a time in the range of 1 to 24 mg, to maintain the target range for Hgb between 10 to 12 g/dL. Dose change values of daprodustat from starting dose at each study time point were calculated as dose level at indicated time point minus starting dose at Day 1 (Baseline).	Day 1 (Baseline), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Number of Participants With 0 to 10, or Greater Than (>) 10 Dose Adjustments	Number of participants who required daprodustat dose adjustments form the starting dose were assessed. Data were categorized for number of participants who required no dose change (0 times) to 10 times and >10 times dose adjustments during the study.	Up to Week 52
Daprodustat Dose at Each Study Time Point	Mean and standard deviation of daprodustat dose received by participants at each study time point has been presented.	Baseline (Day 1), at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Maximum Plasma Concentration (Cmax) of Daprodustat	Blood samples were collected for the plasma concentrations of daprodustat from which pharmacokinetic (PK) parameters were determined. Mean and standard deviation of daprodustat Cmax at steady state obtained via modeling in each sub-trial (requiring Dialysis and not yet requiring Dialysis).	Day 1: 1, 2 and 6 hours Post-dose; Week 2: Pre-dose and 1, 2 and 6 hours Post-dose
Area Under the Curve (AUC) at Steady State of Daprodustat	Blood samples were collected for the plasma concentrations of daprodustat from which PK parameters were determined. Mean and standard deviation of daprodustat AUC at steady state obtained via modeling in each sub-trial (requiring Dialysis and not yet requiring Dialysis).	Day 1: 1, 2 and 6 hours Post-dose; Week 2: Pre-dose and 1, 2 and 6 hours Post-dose
Plasma Concentrations of Daprodustat and Metabolites at Pre-dose (Ctrough)	Blood samples were collected for the plasma concentrations of daprodustat and metabolites from which PK parameters were determined. Mean and standard deviation of raw daprodustat and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401) at steady state at pre-dose obtained via modeling in each sub-trial (requiring Dialysis and not yet requiring Dialysis).	Pre-dose on Week 2

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Actual): October 18, 2024
• Study Completion (Actual): March 17, 2025

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: January 4, 2023
• First Posted (Actual): January 12, 2023

Study Record Updates

• Last Update Posted (Estimated): November 10, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; Chronic kidney disease; Dialysis; Non-dialysis; Daprodustat; ASCEND-P; Erythropoiesis stimulating agent; 214066; 212914
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Renal Insufficiency, Chronic; Anemia; GSK1278863
• Other Study ID Numbers: 214066

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No