special formulation clinical trials

Question 1

• explain the shape of the mAb curve

Answer 1

• snouty bit due to elimination/distribution into tissue
• saturation of targets results in plateau due to target mediated drug disposition
• when mAbs are targeted against internalising receptors , binding to the target may prevent FcRn mediated recylcing

Question 2

• Dosing intervaal

Answer 2

• Chronic disease typically every 2-4 weeks, want targets saturated all the time

Question 3

-What drives eliminaation

Answer 3

• Target accessibility
• How quickly mAbs interact with the target
• rate of target turn over

Question 4

An interim analysis of a IV: SC bioequivalence trial for an mAb shows cause for concern. The efficacy rate has dropped from 98% to 88%. What data would you request from the clinical trials team.

Answer 4

• Patient diary; look for site of injection and compliance
• mAB Concentrations of patients
• Assay for ADA’s in the plasma. Compare efficacy and plasma concentrations of mAB in ADA positive patients and ADA negative patients
• Temperature stability? Did the patients keep them in the fridge