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Model-Informed Supp...
Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients
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- Faraj, Alan (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Le Moan, Natacha (författare)
- Catalyst Biosci, South San Francisco, CA USA.
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- Gorina, Eduard (författare)
- Catalyst Biosci, South San Francisco, CA USA.
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- Blouse, Grant E. E. (författare)
- Catalyst Biosci, South San Francisco, CA USA.
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- Knudsen, Tom (författare)
- Catalyst Biosci, South San Francisco, CA USA.
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- Simonsson, Ulrika S. H., Professor (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- Springer Nature, 2023
- 2023
- Engelska.
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Ingår i: Advances in Therapy. - : Springer Nature. - 0741-238X .- 1865-8652. ; 40:9, s. 3739-3750
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- IntroductionDalcinonacog 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.MethodsA 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.ResultsAlmost 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.ConclusionThis 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- Dalcinonacog alfa
- Population pharmacokinetics
- Hemophilia B
- MID3
- Dose selection
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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