Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients.
Dalcinonacog alfa
Dose selection
Hemophilia B
MID3
Population pharmacokinetics
Journal
Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
02
05
2023
accepted:
26
05
2023
medline:
16
8
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
ppublish
Résumé
Dalcinonacog alfa (DalcA), a novel subcutaneously administered recombinant human factor IX (FIX) variant is being developed for adult and paediatric patients with hemophilia B (HB). DalcA has been shown to raise FIX to clinically meaningful levels in adults with HB. This work aimed to support dosing regimen selection in adults and perform first-in-paediatric dose extrapolations using a model-based pharmacokinetic (PK) approach. A population PK model was built using adult data from two clinical trials (NCT03186677, NCT03995784). With allometry in the model, clinical trial simulations were performed to study alternative dosing regimens in adults and children. Steady-state trough levels and the time-to-reach target were derived to inform dose selection. Almost 90% of the adults were predicted to achieve desirable FIX levels, i.e. 10% FIX activity, following daily 100 IU/kg dosing, with 90% of the subjects reaching target within 1.6-7.1 days. No every-other-day regimen met the target. A dose of 125 IU/kg resulted in adequate FIX levels down to 6 years, whereas a 150 IU/kg dose was needed below 6 down to 2 years of age. For subjects down to 6 years that did not reach target with 125 IU/kg, a dose escalation to 150 IU/kg was appropriate. The children below 6 to 2 years were shown to need a dose escalation to 200 IU/kg if 150 IU/kg given daily was insufficient. This study supported the adult dose selection for DalcA in the presence of sparse data and enabled first-in-paediatric dose selection to achieve FIX levels that reduce risk of spontaneous bleeds.
Identifiants
pubmed: 37341915
doi: 10.1007/s12325-023-02570-6
pii: 10.1007/s12325-023-02570-6
pmc: PMC10427527
doi:
Substances chimiques
Factor IX
9001-28-9
Banques de données
ClinicalTrials.gov
['NCT03186677', 'NCT03995784']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
3739-3750Informations de copyright
© 2023. The Author(s).
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