Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody.
Reilly, M, Miller RM, et alClinical Pharmacology & Therapeutics 2013; 94(5): 593-600
Aims
To provide an initial assessment of the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of OPN-305 after infusing single ascending i.v. doses in healthy adult participants.
Interventions
Participants received either OPN-305 or placebo.
Participants
41 healthy males.
Outcomes
The outcomes included RO assay, IL-6 assay and PK evaluated by measurements of serum drug concentrations.
Follow-up
3 months.
CET Conclusions
This is an important phase one study of OPN-305, a humanised IgG4 monoclonal antibody against the Toll Like Receptor 2 (TLR2). This is a very stable molecule and retains its monospecificity for TLR2. Upregulation of TLR2 is an important part of the inflammatory reaction associated with reperfusion injury and therefore could be important in renal transplantation. Healthy male volunteers have been used and a number of different doses were tested as a single infusion. Even the lowest dose (0.5 mg/kg) produced a 100% occupancy of the TLR2 lasting until day 7 whereas the higher doses, namely 5 and 10mg/kg produced 100% occupancy and complete inhibition of IL6 production for at least 56 days. There were a number of side effects but all relatively minor and the incidence of side effects was exactly the same in the placebo arm. Thus it seemed that all OPN-305 doses were well tolerated and even the lowest dose, namely 0.5mg/KG given as a one hour infusion was adequate to provide 100% of receptor occupancy of TLR2 and 80% inhibition of IL6 release after ex vivo stimulation for up to 14 days in healthy subjects. Thus that would appear to be ideal as a way of preventing ischemia reperfusion injury and the next phase obviously will involve clinical trials in the renal transplant population.
Data analysis
Per protocol analysis
Trial registration
Not reported.