Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial
1
Issued Date
2025-01-01
Resource Type
ISSN
14733099
eISSN
14744457
Scopus ID
2-s2.0-105000772535
Pubmed ID
40015292
Journal Title
The Lancet Infectious Diseases
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Lancet Infectious Diseases (2025)
Suggested Citation
Haidar G., Thomas S., Loubet P., Baker R.I., Benfield T., Boonyaratanakornkit J., Kiertiburanakul S., Kim A.H.J., Longbrake E.E., Molina J.M., Paredes R., Tucker D., Uriel A., Weinmann-Menke J., Aksyuk A.A., Clegg L.E., Currie A., Yang H., Flyrin K., Gibbs M., Shroff M., Perez J.L., Chang L.J., Cohen T.S. Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial. The Lancet Infectious Diseases (2025). doi:10.1016/S1473-3099(24)00804-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/108504
Title
Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial
Author's Affiliation
Génomes, Biologie Cellulaire et Thérapeutique
Manchester University NHS Foundation Trust
Université de Montpellier
University of Washington School of Medicine
Hospital Universitari Germans Trias i Pujol
Washington University School of Medicine in St. Louis
Universitätsmedizin Mainz
Murdoch University
Yale School of Medicine
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Royal Cornwall Hospitals NHS Trust
CASE School of Medicine
AstraZeneca
University of Pittsburgh School of Medicine
AstraZeneca Sweden
Copenhagen University Hospital–Amager and Hvidovre
Hollywood Hospital Haemophilia Treatment Centre
Perth Blood Institute
Chiesi USA
Manchester University NHS Foundation Trust
Université de Montpellier
University of Washington School of Medicine
Hospital Universitari Germans Trias i Pujol
Washington University School of Medicine in St. Louis
Universitätsmedizin Mainz
Murdoch University
Yale School of Medicine
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Royal Cornwall Hospitals NHS Trust
CASE School of Medicine
AstraZeneca
University of Pittsburgh School of Medicine
AstraZeneca Sweden
Copenhagen University Hospital–Amager and Hvidovre
Hollywood Hospital Haemophilia Treatment Centre
Perth Blood Institute
Chiesi USA
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Sipavibart is an anti-spike monoclonal antibody that neutralises SARS-CoV-2 with exceptions, including Phe456Leu-containing variants (eg, KP.2* and KP.3*). This trial assessed sipavibart efficacy and safety for prevention of symptomatic COVID-19 in participants who are immunocompromised. Methods: In this ongoing, double-blind, international, phase 3 trial, we enrolled participants who were immunocompromised and aged 12 years or older at 197 hospitals, university health centres, and clinical trial units in 18 countries. Participants were randomly allocated 1:1 to a sipavibart group (intramuscular sipavibart 300 mg on days 1 and 181) or a comparator group (tixagevimab 300 mg–cilgavimab 300 mg on day 1 and placebo on day 181 or placebo on days 1 and 181), stratified by previous COVID-19 vaccination and infection status and use of tixagevimab–cilgavimab. The primary efficacy outcomes were symptomatic COVID-19 caused by any variant or symptomatic COVID-19 caused by non-Phe456Leu-containing variants within 181 days of dosing, assessed in the SARS-CoV-2-negative set, comprising all participants without a positive RT-PCR test for SARS-CoV-2 at baseline and who received at least one trial intervention dose. Safety outcomes for adverse events were assessed 90 days following the first dose and for serious adverse events throughout the study in the safety analysis set (ie, all participants who received at least one injection of sipavibart or comparator). This study is registered with ClinicalTrials.gov, NCT05648110. Findings: Participants were screened from March 31 to Oct 27, 2023; 3349 participants (56·8% female) were randomly assigned: 1674 to the sipavibart group (five no first dose; 1669 sipavibart) and 1675 to the comparator group (nine no first dose; 1105 tixagevimab–cilgavimab and 561 placebo). Within 181 days of dosing, 122 (7·4%) of 1649 participants in the sipavibart group and 178 (10·9%) of 1631 participants in the comparator group had symptomatic COVID-19 due to any variant (relative risk reduction [RRR] 34·9% [97·5% CI 15·0 to 50·1]; p=0·0006), 54 (3·3%) participants in the sipavibart group and 90 (5·5%) participants in the comparator group had symptomatic COVID-19 due to non-Phe456Leu-containing variants (RRR 42·9% [95% CI 19·9 to 59·3]; p=0·0012), and 47 (2·9%) participants in the sipavibart group and 64 (3·9%) participants in the comparator group had symptomatic COVID-19 due to Phe456Leu-containing variants (30·4% [–1·8 to 52·5]). Adverse events occurred in 833 (49·9%) of 1671 participants in the sipavibart group and 857 (51·5%) of 1663 participants in the comparator group within 3 months of the first dose. One COVID-19-related death occurred in the comparator group. Serious adverse events considered related to trial intervention occurred in two (0·1%) of 1671 participants in the sipavibart group and seven (0·4%) of 1663 participants in the comparator group (none fatal). No serious cardiovascular or thrombotic events were considered to be related to sipavibart. Interpretation: The primary analysis showed efficacy and safety of sipavibart in preventing symptomatic COVID-19 in participants who are immunocompromised when susceptible (ie, non-Phe456Leu-containing) variants dominated, although no efficacy was shown against resistant (ie, Phe456Leu-containing) variants that dominate as of November, 2024. Funding: AstraZeneca.