Module232025

09/05/2025

NCE for Rare syndrome

Agreed PIP

Population pharmacokinetic/pharmacodynamic model aiming to: • Characterise Drug PK and its relationship with the time course of neutrophils and lymphocytes (PD) in adult and adolescent patients with a rare syndrome. • Estimate the PopPK/PD parameters and sources of variability in the population of adults and adolescents, including an extensive covariate analysis. • Identify potential similarities/differences in the PK/PD of adults and adolescents.

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Pediatric extrapolation strategy

PK data in adults (studies XXX-001-A & XXX-001-B)

Serves as basis for

AS *

Dose selection

Dose – PK – PD in adults and adolescents Efficacy / safety –Clinical study XXX-001-100

Predictive PK model in paediatrics (special focus on adolescents)

Pop PK model in adults

M&S Study 1

Serves as basis for

M&S Study 2. Prospective

Fully integrated PK/PD model in adults and adolescents

Incorporation of

Dose – PK– PD in children / comparison with adults Comparison of model predictions with observations allows to validate the predictive capacity of the model in pediatrics 2-<12 y Extrapolation of clinical efficacy/safety from adults to pediatrics

Ontogeny

Allows development of

M&S Study 3 Extrapolation Study. Part 1

Predictive PK/PD model in children Identifications of gaps/uncertainties for extrapolation purposes

Allows establishment of

Fully integrated final predictive PK/PD model (adults & pediatrics ≥2 y)

**

Evaluates and refines

Predictive PK/PD model in children Identifications of gaps/uncertainties for extrapolation

Confirmatory clinical trial in paediatric patients 6-<12 y (N≥8) Clinical study XXX-001-PAED

Confirmatory clinical trial in paediatric patients 2-<6 y (N≥5) Study XXX-002-PAED

Informed predictive PK/PD model (adults & pediatrics ≥6 y)

Evaluates and refines

**

M&S Study 3 Extrapolation. Part 2

*AS: Allometric scaling **If extrapolation cannot address the main uncertainties and assumptions (i.e., if predicted potential PK/PD is not confirmed by observations), predictive PK/PD model and/or trial to be revisited

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