Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method

    Research output: Contribution to journalReviewResearchpeer-review

  2. Ongoing and future COVID-19 vaccine clinical trials: challenges and opportunities

    Research output: Contribution to journalReviewResearchpeer-review

  3. Is oropharyngeal sampling a reliable test to detect SARS-CoV-2?

    Research output: Contribution to journalLetterResearchpeer-review

  4. Specificity and cross-reactivity of a test for anti-SARS-CoV-2 antibodies - Authors' reply

    Research output: Contribution to journalComment/debateResearchpeer-review

  1. Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.

METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.

FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.

INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.

FUNDING: US National Institutes of Health and Operation Warp Speed.

Original languageEnglish
JournalThe Lancet Infectious Diseases
Volume22
Issue number5
Pages (from-to)622-635
Number of pages14
ISSN1473-3099
DOIs
Publication statusPublished - May 2022

Bibliographical note

Copyright © 2021 Elsevier Ltd. All rights reserved.

    Research areas

  • Adolescent, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized/therapeutic use, Antibodies, Neutralizing, COVID-19/drug therapy, Double-Blind Method, Female, Humans, Male, Middle Aged, SARS-CoV-2, Treatment Outcome

ID: 73042883