AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19
77% reduced risk of developing symptomatic COVID-19
First long-acting antibody combination to prevent COVID-19
AZD7442, a combination of two long-acting antibodies (LAAB), reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo. The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis.
There were no cases of severe COVID-19 or COVID-19-related deaths in those treated with AZD7442. In the placebo arm, there were three cases of severe COVID-19, which included two deaths.
AZD7442 is the first antibody combination (non-vaccine) modified to potentially provide long-lasting protection that has demonstrated prevention of COVID-19 in a clinical trial.
The trial included 5,197 participants in a 2:1 randomization AZD7442 to placebo. The primary analysis was based on 5,172 participants who did not have SARS-CoV-2 infection at baseline. More than 75% of participants had co-morbidities, which include conditions that have been reported to cause a reduced immune response to vaccination.
The LAAB was well tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.
AZD7442 was optimized using AstraZeneca’s proprietary YTE half-life extension technology, which could afford up to 12 months of protection from COVID-19, and is delivered by intramuscular injection.
Preliminary ‘in vitro’ findings from investigators at
PROVENT is a Phase III, randomized, double-blind, placebo-controlled, multi-center trial assessing the safety and efficacy of a single 300mg dose of AZD7442 compared to placebo for the prevention of COVID-19. The trial was conducted in 87 sites in the US,
The primary efficacy endpoint was the first case of any SARS-CoV-2 RT-PCR positive symptomatic illness occurring post dose prior to day 183. Subjects will continue to be followed for 15 months.
Participants were adults 18 years-old and over who would benefit from prevention with the LAAB, defined as having increased risk for inadequate response to active immunization (predicted poor responders to vaccines or intolerant of vaccine) or having increased risk for SARS-CoV-2 infection, including those whose locations or circumstances put them at appreciable risk of exposure to the SARS-CoV-2 virus. Participants at the time of screening were unvaccinated and had a negative point-of-care SARS-CoV-2 serology test.
Approximately 43% of participants were 60 years and over. In addition, more than 75% had baseline co-morbidities and other characteristics that are associated with an increased risk for severe COVID-19 should they become infected, including those with immunosuppressive disease or taking immunosuppressive medications, diabetes, severe obesity or cardiac disease, chronic obstructive pulmonary disease, chronic kidney and chronic liver disease. Approximately 73% were White/Caucasian, 17% Black/
AZD7442 is a combination of two LAABs - tixagevimab (AZD8895) and cilgavimab (AZD1061) - derived from B-cells donated by convalescent patients after SARS-CoV-2 virus. Discovered by
AZD7442 is being studied in a comprehensive clinical trial program for both prevention and treatment of COVID-19 in over 9,000 participants. Ongoing trials include TACKLE COVID-1913, a Phase III treatment trial in an outpatient setting and collaborator treatment trials in outpatient and hospitalized settings. AZD7442 is being assessed in both IM and intravenous administration routes.
AZD7442 is being developed with support from the
Data published in Nature in
Under the terms of the licensing agreement with Vanderbilt,
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