Clinical trial NCT05682326: Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anaemia
Keywords: Daprodustat
ASCEND-P
Anemia
Chronic kidney disease
Erythropoiesis stimulating agent
Dialysis
Non-dialysis
214066
212914
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-01-12
Enrollment: 4
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label single arm trial, where all participants are on active treatment with daprodustat.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 56 weeks
measure: Number of participants with adverse event of special interests (AESIs)
timeFrame: Up to 56 weeks
measure: Number of participants with AEs leading to study intervention discontinuation
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Number of participants with change from baseline in laboratory safety parameters
timeFrame: Baseline (Day 1) and up to Week 56
measure: Mean change from baseline in blood pressure (BP)
timeFrame: Baseline (Day 1) and up to Week 56
measure: Mean change from baseline in heart rate (HR)
timeFrame: Baseline (Day 1) and up to Week 56
measure: Mean change from baseline in weight
timeFrame: Baseline (Day 1) and up to Week 56
measure: Mean change from baseline in height
timeFrame: Baseline (Day 1) and up to Week 56
measure: Mean Hgb value
timeFrame: Up to Week 56
measure: Mean change from baseline in Hgb values
timeFrame: Baseline (Day 1) and up to Week 56
measure: Number of participants with Hgb values above, below and within the target range (10 to 12 g/dL)
timeFrame: Up to week 56
measure: Mean daprodustat dose
timeFrame: Up to Week 56
measure: Number of participants with 0 to 10, or greater than [>] 10 dose adjustments
timeFrame: Up to Week 56
measure: Number of participants assigned to each dose level at each visit
timeFrame: Up to Week 56
measure: Maximum plasma concentration (Cmax) of daprodustat and its metabolites
timeFrame: Up to Week 4
measure: Area under the curve (AUC) at steady state of daprodustat and its metabolites
timeFrame: Up to Week 4
measure: Plasma concentrations of daprodustat metabolites at pre-dose trough (Ctrough)
timeFrame: Up to Week 4
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yangsan
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: