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

Anaemia Clinical Trial

— ASCEND-P  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05682326
• Other study ID #: 214066
• Status: Recruiting
• Phase: Phase 3
• Start date: September 6, 2023
• Est. completion date: July 5, 2030

Study information

• Verified date: March 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 5, 2030
• Est. primary completion date: July 5, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anaemia
• Anemia

Intervention

Drug:
• Daprodustat
Daprodustat will be administered up to Week 52.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Liege
France	GSK Investigational Site	Montpellier
France	GSK Investigational Site	Toulouse cedex 9
Italy	GSK Investigational Site	Milano	Lombardia
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Shiga
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Yangsan Gyeongnam
Netherlands	GSK Investigational Site	Rotterdam
Spain	GSK Investigational Site	Esplugues De Llobregat. Barcelona
Spain	GSK Investigational Site	Sevilla
Turkey	GSK Investigational Site	Ankara
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United States	GSK Investigational Site	Amarillo	Texas
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  France,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)	All AEs and SAEs will be collected.	Up to 56 weeks
Primary	Number of participants with adverse event of special interests (AESIs)	All AESI will be collected.	Up to 56 weeks
Primary	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	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
Secondary	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
Secondary	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
Secondary	Mean change from baseline in weight	Weight readings in kilogram (kg) will be collected.	Baseline (Day 1) and up to Week 56
Secondary	Mean change from baseline in height	Height readings in centimeters (cm) will be collected.	Baseline (Day 1) and up to Week 56
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean daprodustat dose	Mean values of daprodustat will be calculated and reported.	Up to Week 56
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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