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Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial.

Publication ,  Journal Article
ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group,
Published in: Lancet Respir Med
October 2022

BACKGROUND: Tixagevimab-cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab-cilgavimab versus placebo, in patients receiving remdesivir and other standard care. METHODS: In a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg-cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab-cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing. FINDINGS: From Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab-cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab-cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97-1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97-1·34]; p=0·13). Mortality was lower in the tixagevimab-cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50-0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab-cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68-1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab-cilgavimab group and 38 (5%) in the placebo group. INTERPRETATION: Among patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab-cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower. FUNDING: US National Institutes of Health (NIH) and Operation Warp Speed.

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Published In

Lancet Respir Med

DOI

EISSN

2213-2619

Publication Date

October 2022

Volume

10

Issue

10

Start / End Page

972 / 984

Location

England

Related Subject Headings

  • Treatment Outcome
  • Humans
  • Double-Blind Method
  • COVID-19 Drug Treatment
  • Antibodies, Neutralizing
  • Antibodies, Monoclonal
  • Adult
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1199 Other Medical and Health Sciences
 

Citation

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ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group, . (2022). Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med, 10(10), 972–984. https://doi.org/10.1016/S2213-2600(22)00215-6
ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group, Annick. “Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial.Lancet Respir Med 10, no. 10 (October 2022): 972–84. https://doi.org/10.1016/S2213-2600(22)00215-6.
ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022 Oct;10(10):972–84.
ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group, Annick. “Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial.Lancet Respir Med, vol. 10, no. 10, Oct. 2022, pp. 972–84. Pubmed, doi:10.1016/S2213-2600(22)00215-6.
ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022 Oct;10(10):972–984.
Journal cover image

Published In

Lancet Respir Med

DOI

EISSN

2213-2619

Publication Date

October 2022

Volume

10

Issue

10

Start / End Page

972 / 984

Location

England

Related Subject Headings

  • Treatment Outcome
  • Humans
  • Double-Blind Method
  • COVID-19 Drug Treatment
  • Antibodies, Neutralizing
  • Antibodies, Monoclonal
  • Adult
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1199 Other Medical and Health Sciences