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

• ClinicalTrials.gov Identifier: NCT05682326
• Recruitment Status: Recruiting
• First Posted: January 12, 2023
• Last Update Posted: March 27, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: January 4, 2023
• First Posted Date: January 12, 2023
• Last Update Posted Date: March 27, 2024
• Actual Study Start Date: September 6, 2023
• Estimated Primary Completion Date: July 5, 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 4, 2023)

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 56 weeks ]
  All AEs and SAEs will be collected.
• Number of participants with adverse event of special interests (AESIs) [ Time Frame: Up to 56 weeks ]
  All AESI will be collected.
• Number of participants with AEs leading to study intervention discontinuation [ Time Frame: Up to 52 weeks ]
  All AEs leading to study intervention discontinuation will be collected.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 4, 2023)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This is an open-label single arm trial, where all participants are on active treatment with daprodustat.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Anaemia

Intervention

Drug: Daprodustat

Daprodustat will be administered up to Week 52.

Study Arms

Experimental: Daprodustat

All participants will receive daprodustat for up to 52 weeks.

Intervention: Drug: Daprodustat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 4, 2023): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 5, 2030
• Estimated Primary Completion Date: July 5, 2030 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Months to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

• Listed Location Countries: Argentina, Belgium, France, Italy, Japan, Korea, Republic of, Netherlands, Spain, Turkey, United Kingdom, United States
• Removed Location Countries: Austria, Canada, Germany, Poland

Administrative Information

• NCT Number: NCT05682326
• Other Study ID Numbers: 214066
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: March 2024