A Phase 3, Randomised, Open-Label, Non-inferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (TwinrabTM) Against Human Rabies Immunoglobulin (HRIG).

BACKGROUND Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to search for alternative therapies. This issue has been addressed by developing an antirabies monoclonal antibody cocktail. METHODS This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with WHO category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, TwinrabTM (docaravimab and miromavimab) or the reference arm, Human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the two arms assessed as percentage of those with rabies virus neutralizing antibodies titers ≥ 0.5 IU/mL on day 14. RESULTS A total of 308 patients were equally randomized into the two arms. In the per-protocol (PP) population, there were 90.21% responders in the TwinrabTM arm and, 94.37% in the HRIG arm. The Geometric Mean of RFFIT titres in the PP on day 14 were 4.38 and 4.85 IU/mL, for the TwinrabTM and HRIG arms, respectively. There were no deaths or serious adverse events reported. CONCLUSIONS This study confirmed that TwinrabTM is non-inferior to HRIG in terms of providing an unbroken window of protection up to day 84. This trial in healthy adults with WHO category III exposure from suspected rabid animal also establishes the safety of TwinrabTM in patients with one WHO approved vaccine regimen (Essen). TRIALS REGISTRATION CTRI/2017/07/009038.