SARS-CoV-2-neutralising antibody BGB-DXP593 in mild-to-moderate COVID-19: a multicentre, randomised, double-blind, phase 2 trial

Ramses Vega; Martti Antila; Carlos Perez; Mohamed Mookadam; Fangjie Xie; Wei Zhang; Ahsan Rizwan; Zhen Yao; John E J Rasko

doi:10.1016/j.eclinm.2023.101832

SARS-CoV-2-neutralising antibody BGB-DXP593 in mild-to-moderate COVID-19: a multicentre, randomised, double-blind, phase 2 trial

EClinicalMedicine. 2023 Mar:57:101832. doi: 10.1016/j.eclinm.2023.101832. Epub 2023 Feb 16.

Authors

Ramses Vega¹, Martti Antila², Carlos Perez³, Mohamed Mookadam⁴, Fangjie Xie⁵, Wei Zhang⁵, Ahsan Rizwan⁶, Zhen Yao⁷, John E J Rasko⁸

Affiliations

¹ Miami Dade Community Services, Inc., Miami, FL, USA.
² Consultoria Médica e Pesquisa Cliníca, Sorocaba, Brazil.
³ Medical Research Center of Miami II, Miami, FL, USA.
⁴ Dr Mookadam and Associates, Langeberg Medicross, Cape Town, South Africa.
⁵ BeiGene Co., Ltd., Shanghai, China.
⁶ BeiGene, Ltd., San Mateo, CA, USA.
⁷ BeiGene (Beijing) Co., Ltd., Beijing, China.
⁸ Gene & Stem Cell Therapy Program, Centenary Institute, and Faculty of Medicine and Health, The University of Sydney, and Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.

Abstract

Background: BGB-DXP593, a neutralising monoclonal antibody against SARS-CoV-2, has demonstrated strong activity in reducing viral RNA copy number in SARS-CoV-2-infected animal models. We aimed to examine the efficacy and safety of BGB-DXP593 in ambulatory patients with mild-to-moderate COVID-19.

Methods: This global, randomised, double-blind, phase 2 study (ClinicalTrials.govNCT04551898) screened patients from 20 sites in Australia, Brazil, Mexico, South Africa, and the USA from December 2, 2020, through January 25, 2021. Patients with a first-positive SARS-CoV-2 test (positive reverse transcription-polymerase chain reaction test or authorised antigen test) ≤3 days before screening and mild-to-moderate COVID-19 symptoms for ≤7 days before treatment were randomised 1:1:1:1 to receive a single intravenous infusion of BGB-DXP593 5, 15, or 30 mg/kg, or placebo. The primary endpoint was change from baseline to Day 8 in viral RNA copies/mL as measured in nasopharyngeal swabs. Secondary endpoints were hospitalisation rate due to worsening COVID-19 and treatment-emergent adverse events (TEAEs). A prespecified exploratory endpoint was change in viral RNA copy number in saliva.

Findings: Relative to the natural rate of clearance as assessed in placebo-exposed patients (-3.12 log₁₀ copies/mL), no significant differences in nasopharygneal viral RNA copy number changes were observed (-2.93 to -3.63 log₁₀ copies/mL) by Day 8 in BGB-DXP593-treated patients. Reductions from baseline to Day 8 in saliva viral RNA copy number were larger with BGB-DXP593 5 mg/kg (-1.37 log₁₀ copies/mL [90% confidence interval -2.14, -0.61]; nominal p = 0.003) and 15 mg/kg (-1.26 [-2.06, -0.46]; nominal p = 0.01) vs placebo, and differences favoring BGB-DXP593 were observed by Day 3, although not statistically significant; no difference from placebo was observed for BGB-DXP593 30 mg/kg (-0.71 [-1.45, 0.04]; nominal p = 0.12). Hospitalisation rate due to COVID-19 was numerically lower with BGB-DXP593 (pooled: 2/134 patients; 1.5%) vs placebo (2/47 patients; 4.3%), although not statistically significant. Incidence of TEAEs was similar across treatment groups. No TEAE led to treatment discontinuation. Five serious TEAEs occurred, all attributed to COVID-19 pneumonia.

Interpretation: BGB-DXP593 was well tolerated. Although nasopharyngeal swab SARS-CoV-2 viral RNA copy number was not significantly decreased compared with placebo, viral RNA copy number was inconsistently reduced by Day 8 in saliva at some doses as low as 5 mg/kg.

Funding: BeiGene, Ltd.

Keywords: BGB-DXP593; COVID-19; Neutralising monoclonal antibody; Phase 2 trial; SARS-CoV-2; Viral load or viral RNA copy number.

Associated data

ClinicalTrials.gov/NCT04551898