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

Phase 3
Completed
Conditions
Anaemia
Interventions
Registration Number
NCT05682326
Lead Sponsor
GlaxoSmithKline
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
4
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
DaprodustatDaprodustatAll participants will receive daprodustat for up to 52 weeks.
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events (AEs) and serious adverse events (SAEs)Up to 56 weeks

All AEs and SAEs will be collected.

Number of participants with AEs leading to study intervention discontinuationUp to 52 weeks

All AEs leading to study intervention discontinuation will be collected.

Number of participants with adverse event of special interests (AESIs)Up to 56 weeks

All AESI will be collected.

Secondary Outcome Measures
NameTimeMethod
Mean change from baseline in weightBaseline (Day 1) and up to Week 56

Weight readings in kilogram (kg) will be collected.

Mean change from baseline in heightBaseline (Day 1) and up to Week 56

Height readings in centimeters (cm) will be collected.

Maximum plasma concentration (Cmax) of daprodustat and its metabolitesUp to Week 4

Blood samples will be collected for the plasma concentrations of daprodustat from which PK parameters will be determined.

Plasma concentrations of daprodustat metabolites at pre-dose trough (Ctrough)Up to Week 4

Blood samples will be collected for the plasma concentrations of daprodustat metabolites from which PK parameters will be determined.

Mean change from baseline in blood pressure (BP)Baseline (Day 1) and up to Week 56

Blood pressure readings in millimeters of mercury (mmHg) will be collected.

Mean change from baseline in heart rate (HR)Baseline (Day 1) and up to Week 56

Heart rate readings in beats per minutes (bpm) will be collected.

Number of participants with Hgb values above, below and within the target range (10 to 12 g/dL)Up to week 56

Number of participants with Hgb values above, below, and within the target range (10 to 12g/dL) will be assessed.

Number of participants with change from baseline in laboratory safety parametersBaseline (Day 1) and up to Week 56

Number of participants with abnormal laboratory safety parameters will be assessed.

Mean Hgb valueUp to Week 56

Blood samples will be collected from all participants for measurement of Hgb (grams per deciliter \[g/dL\]) values.

Mean change from baseline in Hgb valuesBaseline (Day 1) and up to Week 56

Blood samples will be collected from all participants for measurement of Hgb (g/dL) values.

Number of participants assigned to each dose level at each visitUp to Week 56

Number of participants assigned to each dose level of dapurodustat will be assessed

Area under the curve (AUC) at steady state of daprodustat and its metabolitesUp to Week 4

Blood samples will be collected for the plasma concentrations of daprodustat from which PK parameters will be determined.

Mean daprodustat doseUp to Week 56

Mean values of daprodustat will be calculated and reported.

Number of participants with 0 to 10, or greater than [>] 10 dose adjustmentsUp to Week 56

Number of participants with 0 to 10, or \>10 dose adjustments form the starting dose of dapurodustat will be assessed.

Trial Locations

Locations (1)

GSK Investigational Site

🇰🇷

Yangsan, Korea, Republic of

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