A Study of Immune System Proteins in Participants With Mild to Moderate COVID-19 Illness

Summary

The purpose of this study is to measure how well monoclonal antibodies work, either alone or in combination, against the virus that causes COVID-19. Study drug(s) will be given to participants with early symptoms of COVID-19. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 or 24 weeks and includes at least 1 visit to the study site, with the remainder of assessments performed in the home, local clinic, or by phone.

Timeline

Start

2020-10-29

Primary completion

2021-07-27

Completion

2021-10-18

Outcome

Mixed primary results

registry analysis (superiority test); Treatment 1: Pbo vs Treatment 2: 175 mg BAM +350 mg ETE; p = 0.009273; Odds Ratio (OR) 0.37 (95% CI 0.18 to 0.78); Regression, Logistic NCT04634409 ↗

registry analysis (superiority test); Treatment 1: Pbo vs Unintentional Dosing: 700 mg BAM +700 mg ETE; p = 0.140563; Odds Ratio (OR) 0.35 (95% CI 0.09 to 1.41); Regression, Logistic NCT04634409 ↗

registry analysis (superiority test); Treatment 9: 175 mg BEB (Amendment (f), Low Risk Participants) vs Treatment 11: Pbo For 175 mg BEB & 700 mg BAM +1400 mg ETE +175 mg BEB (Low Risk Participants); p = 0.097231; Odds Ratio (OR) 0.56 (95% CI 0.28 to 1.11); Regression, Logistic NCT04634409 ↗

paper A significantly lower proportion of patients in arms 2-6 and arm 7 experienced PHVL on day 7 compared to placebo. PMID 38291279 ↗

Publications

• Nichols RM, Macpherson L, Patel DR, Yeh WW, Peppercorn A. Effect of Bamlanivimab as Monotherapy or in Combination with Etesevimab or Sotrovimab on Persistently High Viral Load in Patients with Mild-to-Moderate COVID-19: A Randomized, Phase 2 BLAZE-4 Trial. Infect Dis Ther. 2024 Feb;13(2):401-411. doi: 10.1007/s40121-024-00918-1. Epub 2024 Jan 30.
• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
• 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.
• Nathan R, Shawa I, De La Torre I, Pustizzi JM, Haustrup N, Patel DR, Huhn G. A Narrative Review of the Clinical Practicalities of Bamlanivimab and Etesevimab Antibody Therapies for SARS-CoV-2. Infect Dis Ther. 2021 Dec;10(4):1933-1947. doi: 10.1007/s40121-021-00515-6. Epub 2021 Aug 10.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Bamlanivimab	Monoclonal antibody	175 mg	Intravenous
Subject	Bamlanivimab	Monoclonal antibody	350 mg	Intravenous
Subject	Bamlanivimab	Monoclonal antibody	700 mg	Intravenous
Subject	Bamlanivimab	Monoclonal antibody	2800 mg	Intravenous
Subject	Bebtelovimab	Monoclonal antibody	70 mg	Intravenous
Subject	Bebtelovimab	Monoclonal antibody	175 mg	Intravenous
Subject	Bebtelovimab	Monoclonal antibody	280 mg	Intravenous
Subject	Bebtelovimab	Monoclonal antibody	560 mg	Intravenous
Subject	Bebtelovimab	Monoclonal antibody	1400 mg	Intravenous
Subject	Bebtelovimab	Monoclonal antibody	1750 mg	Intravenous
Subject	Etesevimab	Monoclonal antibody	350 mg	Intravenous
Subject	Etesevimab	Monoclonal antibody	700 mg	Intravenous
Subject	Etesevimab	Monoclonal antibody	1400 mg	Intravenous
Subject	Etesevimab	Monoclonal antibody	2800 mg	Intravenous
Subject	Sotrovimab	Monoclonal antibody	500 mg	Intravenous

Indications