A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.

ABSTRACT:

Background

Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg.

Methods

Using the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency. Simulations were then performed to identify the minimal exposure expected to achieve zero bleeding events for 1 year in at least 50% of patients and to select the dosing regimens to be t

SUBMITTER: Yoneyama K 

PROVIDER: S-EPMC6061395 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature