Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial
Authors: Hites Maya , Massonnaud Clément R. , Jamard Simon , Goehringer François , Danion François , Reignier Jean , de Castro Nathalie , Garot Denis , Larranaga Lapique Eva , Lacombe Karine , Tolsma Violaine , Faure Emmanuel , Malvy Denis , Staub Thérèse , Courjon Johan , Cazenave-Roblot France , Dyrhol Riise Anne Ma , Leturnier Paul , Martin-Blondel Guillaume , Roger Claire , Akinosoglou Karolina , Le Moing Vincent , Piroth Lionel , Sellier Pierre , Lescure Xavier , Trøseid Marius , Clevenbergh Philippe , Dalgard Olav , Gallien Sébastien , Gousseff Marie , Loubet Paul , Vardon-Bounes Fanny , Visée Clotilde , Belkhir Leila , Botelho-Nevers Élisabeth , Cabié André , Kotanidou Anastasia , Lanternier Fanny , Rouveix-Nordon Elisabeth , Silva Susana , Thiery Guillaume , Poignard Pascal , Carcelain Guislaine , Diallo Alpha , Mercier Noémie , Terzic Vida , Bouscambert-Duchamp Maude , Gaymard Alexandre , Trabaud Marie Anne , Destras Grégory , Josset Laurence , Belhadi Drifa , Billard Nicolas , Guedj Jérémie , Han Thi-Hong-Lien , Couffin-Cadiergues Sandrine , Dechanet Aline , Delmas Christelle , Esperou Hélène , Fougerou-Leurent Claire , Mestre Soizic Le , Métois Anabelle , Noret Marion , Bally Isabelle , Dergan-Dylon Sebastián , Tubiana Sarah , Kalif Ouifiya , Bergaud Nathalie , Leveau Benjamin , Eustace Joe , Greil Richard , Hajdu Edit , Halanova Monika , Paiva Jose-Artur , Piekarska Anna , Rodriguez Baño Jesus , Tonby Kristian , Trojánek Milan , Tsiodras Sotirios , Unal Serhat , Burdet Charles , Costagliola Dominique , Yazdanpanah Yazdan , Peiffer-Smadja Nathan , Mentré France , Ader Florence 
Published: December 2024

Background

Tixagevimab and cilgavimab (AZD7442) are two monoclonal antibodies developed by AstraZeneca for the pre-exposure prophylaxis and treatment of patients infected by SARS-CoV-2. Its effectiveness and safety in patients hospitalized with COVID-19 was not known at the outset of this trial.

Methods

DisCoVeRy is a phase 3, adaptive, multicentre, randomized, controlled trial conducted in 63 sites in Europe. Participants were randomly assigned (1:1) to receive placebo or tixagevimab-cilgavimab in addition to standard of care. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale. Several clinical, virological, immunological and safety endpoints were also assessed.

Findings

Due to slow enrolment, recruitment was stopped on July 1st, 2022. The antigen positive modified intention-to-treat population (mITT) was composed of 173 participants randomized to tixagevimab-cilgavimab (N = 91) or placebo (N = 82), 91.9% (159/173) with supplementary oxygen, and 47.4% (82/173) previously vaccinated at inclusion. There was no significant difference in the distribution of the WHO ordinal scale at day 15 between the two groups (odds ratio (OR) 0.93, 95%CI [0.54-1.61]; p = 0.81) nor in any clinical, virological or safety secondary endpoints. In the global mITT (N = 226), neutralization antibody titers were significantly higher in the tixagevimab-cilgavimab group/patients compared to placebo at day 3 (Least-squares mean differences (LSMD) 1.44, 95% Confidence interval (CI) [1.20-1.68]; p < 10−23) and day 8 (LSMD 0.91, 95%CI [0.64-1.18]; p < 10−8) and it was most important for patients infected with a pre-omicron variant, both at day 3 (LSMD 1.94, 95% CI [1.67-2.20], p < 10−25) and day 8 (LSMD 1.17, 95% CI [0.87-1.47], p < 10−9), with a significant interaction (p < 10−7and p = 0.01 at days 3 and 8, respectively).

Interpretation

There were no significant differences between tixagevimab-cilgavimab and placebo in clinical endpoints, however the trial lacked power compared to prespecified calculations. Tixagevimab-cilgavimab was well tolerated, with low rates of treatment related events.

Funding

Trial registration:ClinicalTrials.govNCT04315948. Registered on 13 March 2020 updated on 22 April 2021.