This modeling and simulation analysis was aimed at selecting doses of cinpanemab (BIIB054), a monoclonal antibody targeting aggregated α‐synuclein, for a phase II study in Parkinson’s disease (PD). Doses and regimens were proposed based on anticipated target concentration in brain interstitial fluid (ISF); in vitro/in vivo data on the affinity of monoclonal antibodies to the target protein; and safety, tolerability, and pharmacokinetic data (1–135?mg/kg intravenous administration) from a phase I single ascending dose (SAD) study. A population pharmacokinetic modeling approach was used to select intravenous doses of 250, 1,250, and 3,500?mg every 4?weeks, to maintain 50%, 90%, and ?90% of target binding in ISF of PD participants. A favorable safety profile from the SAD study—which showed that cinpanemab was generally well‐tolerated at doses up to 90?mg/kg, supported by modeling and simulations of the anticipated safety margins—allowed implementation of a fixed‐dose approach.
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