Intramuscular and Intravenous VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19.

Summary

The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over different infusion times when given for the treatment of mild/moderate COVID-19 to participants at high risk of disease progression Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.

Timeline

Start

2021-06-10

Primary completion

2022-07-19

Completion

2023-03-24

Outcome

Met primary endpoint

Stopped: “The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes”

paper Sotrovimab 500 mg IM was noninferior to 500 mg IV PMID 37577112 ↗

paper The 95% CI upper limit was lower than the prespecified noninferiority margin of 3.5%. PMID 37577112 ↗

release “COMET-TAIL Phase 3 trial, which achieved its primary endpoint, demonstrating intramuscular (IM) administration of sotrovimab was non-inferior to intravenous (IV) administration” vir.bio ↗

release “The companies also recently announced headline data from the randomised, multi-centre, open-label COMET-TAIL Phase III trial, which achieved its primary endpoint” gsk.com ↗

release “COMET-TAIL trial, which achieved its primary endpoint” vir.bio ↗

Publications

• Shapiro AE, Sarkis E, Acloque J, Free A, Gonzalez-Rojas Y, Hussain R, Juarez E, Moya J, Parikh N, Inman D, Cebrik D, Nader A, Noormohamed N, Wang Q, Skingsley A, Austin D, Peppercorn A, Agostini ML, Parra S, Chow S, Mogalian E, Pang PS, Hong DK, Sager JE, Yeh WW, Alexander EL, Gaffney LA, Kohli A. Intramuscular vs Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Noninferiority Clinical Trial. Open Forum Infect Dis. 2023 Jul 14;10(8):ofad354. doi: 10.1093/ofid/ofad354. eCollection 2023 Aug.
• Moya J, Temech M, Parra S, Juarez E, Hernandez-Loy R, Gutierrez JCM, Diaz J, Hussain R, Segal S, Xu C, Skingsley A, Schnell G, El-Zailik A, Sager JE, Aldinger M, Alexander EL, Acloque G. Safety, Virology, Pharmacokinetics, and Clinical Experience of High-Dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-Label Clinical Trial. Open Forum Infect Dis. 2023 Jul 10;10(7):ofad344. doi: 10.1093/ofid/ofad344. eCollection 2023 Jul.
• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Sotrovimab	Monoclonal antibody	250 mg	Intravenous
Subject	Sotrovimab	Monoclonal antibody	500 mg	Intravenous
Subject	Sotrovimab	Monoclonal antibody	2000 mg	Intravenous
Subject	Sotrovimab	Monoclonal antibody	3000 mg	Intravenous

Indications