Protocol for Trial of Daprodustat for Anemia in Pediatric Patients With CKD

Children with advanced chronic kidney disease (CKD) commonly experience anemia of CKD, resulting in significant impact on quality of life, developmental milestones, and physical activity. Managing pediatric anemia of CKD with erythropoietins that require regular injection is challenging. Daprodustat, a hypoxia-inducible factor prolyl hydroxylase enzyme inhibitor, has demonstrated noninferiority for both efficacy and safety in adults with anemia of CKD, in both dialysis and nondialysis populations, and is administered by mouth.

During a poster session at the NKF 2023 Spring Clinical Meetings, Thomas F. Hiemstra, MD, PhD, and colleagues described protocol for a global trial of daprodustat for treatment for anemia in patients 3 months to 17 years with CKD stage ≥3. The poster was titled Protocol for Erythropoiesis via a Novel PHI Daprodustat–Pediatric (ASCEND-P) Trial.

The global, prospective, single-arm, interventional basket trial will consist of two subtrials of 60 patients receiving dialysis and 60 patients not receiving dialysis. Each subtrial will include an integrated 4-week pharmacokinetic (PK) phase in up to 24 participants, allowing in-trial adaptation of the dosing strategy if actual PK deviates from model assumptions.

Participants will be treated with oral daprodustat to achieve a target hemoglobin concentration of 10-12 g/dL. Participants will be followed every 4 weeks for 28 weeks and then every 4 to 8 weeks for 56 weeks. Recruitment will be from the CoCOA-CKD prospective cohort study of anemia in children with CKD.

The primary outcome of interest is the safety of daprodustat in a pediatric population, determined by the incidence of adverse events, serious adverse events, and adverse events of special interest. Hemoglobin response and PK are secondary outcomes.

In summary, the researchers said, “The ASCEND-P single-arm basket trial of daprodustat for anemia of CKD will evaluate the safety and efficacy of daprodustat in both dialysis and predialysis pediatric patients. The design of the ASCEND-P study as a basket trial within a basket cohort study, with an adaptive approach to PK, provides an efficient and patient-centered way to evaluate the use of daprodustat as an oral agent for the treatment of anemia in CKD in pediatric populations.”

The study is funded by GSK(Study 214066).

Source: Hiemstra TF, Vick JG, Roberts JC. Protocol for the erythropoiesis via a novel PHI daprodustat­–pediatric (ASCEND-P) trial. Poster #181. Abstract of a poster presented at the National Kidney Foundation Spring Clinical Meetings 2023; April 11-15, 2023; Austin, Texas.