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
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | The Lancet Infectious Diseases |
| Vol/bind | 22 |
| Udgave nummer | 5 |
| Sider (fra-til) | 622-635 |
| Antal sider | 14 |
| ISSN | 1473-3099 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Medications used in the trial were supplied by Vir/GlaxoSmithKline (sotrovimab), Brii Biosciences (BRII-196 plus BRII-198), and Gilead Sciences (remdesivir). This trial was supported by the US Operation Warp Speed programme, NIAID and Leidos Biomedical Research for the INSIGHT Network, NHLBI, the Research Triangle Institute for the Prevention and Early Treatment of Acute Lung Injury Network, Cardiothoracic Surgical Trials Network, the Office of Research & Development, and US Department of Veterans Affairs, and grants from the governments of Denmark (number 126 from the National Research Foundation), Australia (from the National Health and Medical Research Council), and the United Kingdom (MRC_UU_12023/23 from the MRC). This research was, in part, funded by the NIH (agreement 1OT2HL156812-01). AV was supported in part by grants provided by NHLBI (5T32HL069749-17). JMS was supported in part by grants from National Center for Advancing Translational Sciences (UL1TR003015 and KL2TR003016). JDC was supported in part by a grant from NHLBI (K23HL153584). BWT was supported in part by the US Department of Veterans Affairs, Office of Research & Development, and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). The work at Massachusetts General Hospital was supported in part by the Harvard Catalyst/Harvard Clinical and Translational Science Center (NCATS, NIH awards UL1TR001102 and UL1TR002541–01). This research was, in part, funded by the NIH, including agreement 1OT2HL156812-01. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing official policies, either expressed or implied, of the NIH or Department of Veterans Affairs.
Funding Information:
Medications used in the trial were supplied by Vir/GlaxoSmithKline (sotrovimab), Brii Biosciences (BRII-196 plus BRII-198), and Gilead Sciences (remdesivir). This trial was supported by the US Operation Warp Speed programme, NIAID and Leidos Biomedical Research for the INSIGHT Network, NHLBI, the Research Triangle Institute for the Prevention and Early Treatment of Acute Lung Injury Network, Cardiothoracic Surgical Trials Network, the Office of Research & Development, and US Department of Veterans Affairs, and grants from the governments of Denmark (number 126 from the National Research Foundation), Australia (from the National Health and Medical Research Council), and the United Kingdom (MRC_UU_12023/23 from the MRC). This research was, in part, funded by the NIH (agreement 1OT2HL156812-01). AV was supported in part by grants provided by NHLBI (5T32HL069749-17). JMS was supported in part by grants from National Center for Advancing Translational Sciences (UL1TR003015 and KL2TR003016). JDC was supported in part by a grant from NHLBI (K23HL153584). BWT was supported in part by the US Department of Veterans Affairs, Office of Research & Development, and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). The work at Massachusetts General Hospital was supported in part by the Harvard Catalyst/Harvard Clinical and Translational Science Center (NCATS, NIH awards UL1TR001102 and UL1TR002541–01). This research was, in part, funded by the NIH, including agreement 1OT2HL156812-01. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing official policies, either expressed or implied, of the NIH or Department of Veterans Affairs.
Publisher Copyright:
© 2022 Elsevier Ltd
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700279/pdf/main.pdf
Forlagets udgivne version
ID: 345018408