A Phase 3, Randomized, Open-label, Noninferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (Twinrab™) 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 anti-rabies monoclonal antibody cocktail. Methods. This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with World Health Organization (WHO) category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, Twinrab (TM) (docaravimab and miromavimab) or the reference arm, human rabies immunoglobulin (HRIG; Imogam (R) Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the 2 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 2 arms. In the per-protocol (PP) population, there were 90.21% responders in the Twinrab (TM) arm and 94.37% in the HRIG arm. The geometric mean of rapid fluorescent foci inhibition test titers in the PP on day 14 were 4.38 and 4.85 IU/mL, for the Twinrab (TM) and HRIG arms, respectively. There were no deaths or serious adverse events reported. Conclusions. This study confirmed that Twinrab (TM) is noninferior 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 Twinrab (TM) in patients with 1 WHO approved vaccine regimen (Essen).

Automated summary

This study confirmed the noninferiority of Twinrab (TM) compared to HRIG in providing continuous protection up to day 84. There were differences in responder rates and rabies virus neutralizing antibodies titers between the two arms, but no serious adverse events were reported.