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Updated: Feb 19, 2026
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Dose Selection Based on Modeling and Simulation for Rivipansel in Pediatric Patients Aged 6 to 11 Years With Sickle
Brinda K Tammara1, Lutz O Harnisch2
1Pfizer, Collegeville, Pennsylvania, USA.
Insights
This study recommends a rivipansel dosing regimen for children with sickle cell disease (SCD). A 40-mg/kg loading dose followed by 20-mg/kg every 12 hours is predicted to be effective.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Hematology
Background:
- Sickle cell disease (SCD) is a genetic blood disorder requiring effective treatments.
- Rivipansel is an investigational drug for managing SCD complications.
- Pediatric dosing for rivipansel needs optimization for Phase III trials.
Purpose of the Study:
- To establish optimal rivipansel dosing recommendations for pediatric patients (6-11 years) with SCD.
- To ensure therapeutic drug concentrations in children based on existing pharmacokinetic data.
- To support the design of upcoming Phase III clinical studies.
Main Methods:
- A three-compartmental pharmacokinetic model was developed using data from 109 adult and adolescent patients.
- Simulations incorporated age-specific renal function and hyperfiltration in SCD.
- Predicted drug concentrations from three regimens were compared to Phase II efficacy targets.
Main Results:
- A dosing regimen of a 40-mg/kg loading dose followed by a 20-mg/kg maintenance dose every 12 hours was identified.
- This regimen is predicted to achieve efficacious average steady-state concentrations in pediatric SCD patients.
- The selected regimen is expected to provide a therapeutic concentration range.
Conclusions:
- The proposed rivipansel dosing regimen is suitable for Phase III pediatric SCD studies.
- Further validation of this dosing strategy will occur during the ongoing Phase III trial.
- This modeling exercise provides a data-driven approach to pediatric drug development for SCD.
Abstract:
This modeling and simulation exercise aimed to provide dosing recommendations for rivipansel phase III studies in children aged 6-11 years with sickle cell disease (SCD). Pharmacokinetic data from 109 patients aged 12-51 years who received rivipansel (2-40 mg/kg) in previous studies (three phase I and one phase II) were integrated to build a three-compartmental simulation model. Renal clearance simulations across the age range accounted for renal function development and postulated hyperfiltration in SCD. Simulated demographic distributions for the pediatric SCD population were used to predict concentration-time profiles from three dosing regimens, which were then compared against efficacious average steady-state concentrations observed in phase II. A dosing regimen comprising a 40-mg/kg loading dose followed by a 20-mg/kg maintenance dose every 12 hours was selected, as it will likely provide an efficacious concentration range. Its validity will be confirmed in the ongoing phase III study.
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