A Phase 3, Randomized, Open-label, Noninferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (TwinrabTM) Against Human Rabies Immunoglobulin (HRIG). (17th June 2020)

• Record Type: Journal Article
• Authors: Kansagra, Kevinkumar; Parmar, Deven; Mendiratta, Sanjeev Kumar; Patel, Jatin; Joshi, Shuchi; Sharma, Nitin; Parihar, Anurag; Bhoge, Swapnil; Patel, Harilal; Kalita, Pankaj; Munshi, Renuka; Kurmi, Prakash; Shah, Ruchir; Gupta, Abhishek; Bhalla, HiraLal; Bekkalele, Harish; Verma, RajendraKumar; Agarwal, Dinesh; Sharma, Shrikant; Gawande, Avinash; Chhaya, Gaurav
• Is Part Of: Clinical infectious diseases. Volume 73:Number 9(2021)
• Page Start: e2722
• Page End: e2728
• Publication Date: 2020-06-17
• Subjects: monoclonal antibodies -- rabies -- post exposure prophylaxis -- clinical trial; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa779
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: 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 ® 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). Clinical Trials Registration: CTRI/2017/07/009038. Abstract : We established clinical noninferiority of Twinrab TM (anti-rabies monoclonal antibody cocktail) to human rabies immunoglobulin (HRIG) by providing adequate postexposure prophylaxis to patients following a suspected category III rabies exposure.