Abstract: LB5. PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/
Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults
Myron J. Levin, MD1; Andrew Ustianowski, MBBS2;
Stéphane De Wit, MD3; Odile Launay, MD, PhD4; Miles Avila, MPH, GStat5;
Seth Seegobin, PhD5; Alison Templeton, PhD5; Yuan Yuan, PhD6;
Philip Ambery, FRCP5; Rosalinda H. Arends, PhD5; Rohini Beavon, PhD5;
Karen A. Near, MD5; Kelly W. Padilla, PharmD5; Konstantina Psachoulia, PhD5;
Audrey Sharbaugh, PhD5; Katie Streicher, PhD5; Menelas N. Pangalos, PhD5;
Mark T. Esser, PhD5; Robert A. Gasser, Jr., MD5; 1University of Colorado Anschutz
Medical Campus, Aurora, CO; 2North Manchester General Hospital, Manchester,
England, United Kingdom; 3CHU St-Pierre, Brussels, Brussels Hoofdstedelijk Gewest,
Belgium; 4Université de Paris, Inserm F-CRIN I-REIVAC, Paris, Ile-de-France,
France; 5AstraZeneca, Gaithersburg, Maryland; 6AstraZeneca, Gaithersburg, MD,
USA, Gaithersburg, Maryland
Session: 55. Late Breaker Abstracts: COVID-19 Treatment & Prophylaxis
Thursday, September 30, 2021: 6:15 PM
Background. Vaccines effectively prevent COVID-19, but some individuals
have medical comorbidities or receive therapies that impair their immune response
to vaccination, or are ineligible for vaccination. For such individuals who remain at
risk of COVID-19, monoclonal antibodies may provide additional rapid protection.
AZD7442 comprises 2 fully human extended half-life SARS-CoV-2–neutralizing antibodies that bind distinct epitopes of the viral spike protein receptor binding domain.
AZD7442 is in development for the prevention and treatment of COVID-19. Here,
we report primary Phase 3 study results of AZD7442 for pre-exposure prophylaxis of
symptomatic COVID-19.
Methods. PROVENT (NCT04625725) is a Phase 3, 2:1 randomized,
double-blind, placebo-controlled study of a single 300-mg AZD7442 dose (2 intramuscular injections; 150 mg each of tixagevimab and cilgavimab) for symptomatic COVID-19 prevention. Participants were unvaccinated adults (≥ 18 years old)
without prior SARS-CoV-2 infection, who may benefit from immunoprophylaxis with
antibodies due to an increased risk of either inadequate response to vaccination or
SARS-CoV-2 exposure. The primary study endpoints were first case of SARS-CoV-2
RT-PCR-positive symptomatic illness post dose and prior to Day 183 (efficacy), and
safety of AZD7442.
Results. In total, 5197 participants (mean age 53.5 years, 46% female) were randomized and dosed (safety analysis set): AZD7442 n=3460; placebo n=1737. In the
primary efficacy analysis (full pre-exposure analysis set, n=5172), AZD7442 reduced
the risk of developing symptomatic COVID-19 by 77% (95% confidence interval
S810 • OFID 2021:8 (Suppl 1) • Late Breaking Abstracts
46.0, 90.0) vs placebo (P< 0.001) (Table). Adverse events occurred in 35% and 34%
of participants administered AZD7442 and placebo, respectively, and injection site
reactions occurred in 2.4% and 2.1% of participants, respectively (safety analysis set).
There was 1 case of severe/critical COVID-19 and 2 COVID-19–related deaths in
the placebo arm.
Conclusion. The primary study endpoints were met: a one-time dose of AZD7442
demonstrated statistically significant protection against symptomatic COVID-19 and
was well tolerated. AZD7442 is the first long-acting monoclonal antibody combination
that represents a potential new option to augment COVID-19 prevention.
PROVENT funding statement image
Disclosures. Myron J. Levin, MD, GSK..
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Vaccines effectively prevent COVID-19, but some individuals have '
'medical comorbidities or receive therapies that impair their immune response to vaccination, '
'or are ineligible for vaccination. For such individuals who remain at risk of COVID-19, '
'monoclonal antibodies may provide additional rapid protection. AZD7442 comprises 2 fully '
'human extended half-life SARS-CoV-2–neutralizing antibodies that bind distinct epitopes of '
'the viral spike protein receptor binding domain. AZD7442 is in development for the prevention '
'and treatment of COVID-19. Here, we report primary Phase 3 study results of AZD7442 for '
'pre-exposure prophylaxis of symptomatic COVID-19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>PROVENT (NCT04625725) is a Phase 3, 2:1 randomized, double-blind, '
'placebo-controlled study of a single 300-mg AZD7442 dose (2 intramuscular injections; 150 mg '
'each of tixagevimab and cilgavimab) for symptomatic COVID-19 prevention. Participants were '
'unvaccinated adults (≥ 18 years old) without prior SARS-CoV-2 infection, who may benefit from '
'immunoprophylaxis with antibodies due to an increased risk of either inadequate response to '
'vaccination or SARS-CoV-2 exposure. The primary study endpoints were first case of SARS-CoV-2 '
'RT-PCR-positive symptomatic illness post dose and prior to Day 183 (efficacy), and safety of '
'AZD7442.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>In total, 5197 participants (mean age 53.5 years, 46% female) were '
'randomized and dosed (safety analysis set): AZD7442 n=3460; placebo n=1737. In the primary '
'efficacy analysis (full pre-exposure analysis set, n=5172), AZD7442 reduced the risk of '
'developing symptomatic COVID-19 by 77% (95% confidence interval 46.0, 90.0) vs placebo '
'(P&lt; 0.001) (Table). Adverse events occurred in 35% and 34% of participants '
'administered AZD7442 and placebo, respectively, and injection site reactions occurred in 2.4% '
'and 2.1% of participants, respectively (safety analysis set). There was 1 case of '
'severe/critical COVID-19 and 2 COVID-19–related deaths in the placebo arm.</jats:p>\n'
' <jats:p />\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusion</jats:title>\n'
' <jats:p>The primary study endpoints were met: a one-time dose of AZD7442 '
'demonstrated statistically significant protection against symptomatic COVID-19 and was well '
'tolerated. AZD7442 is the first long-acting monoclonal antibody combination that represents a '
'potential new option to augment COVID-19 prevention.</jats:p>\n'
' <jats:p>PROVENT funding statement image</jats:p>\n'
' <jats:p />\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Disclosures</jats:title>\n'
' <jats:p>Myron J. Levin, MD, GSK group of companies (Employee, Research '
'Grant or Support) Andrew Ustianowski, MBBS, Vir/GlaxoSmithKline (Advisor or Review Panel '
'member) Stéphane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research '
'Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research '
'Support) Odile Launay, MD, PhD, AstraZeneca (Grant/Research Support)GlaxoSmithKline '
'(Consultant, Grant/Research Support, Other Financial or Material Support, Data safety '
'monitoring board)Johnson & Johnson (Consultant, Grant/Research Support)Moderna '
'(Consultant)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, '
'Grant/Research Support) Miles Avila, MPH, GStat, AstraZeneca (Employee, Shareholder) Seth '
'Seegobin, PhD, AstraZeneca (Employee, Shareholder) Alison Templeton, PhD, AstraZeneca '
'(Employee, Shareholder) Yuan Yuan, PhD, AstraZeneca (Employee, Shareholder) Philip Ambery, '
'FRCP, AstraZeneca (Employee, Shareholder) Rosalinda H. Arends, PhD, AstraZeneca (Employee, '
'Shareholder) Rohini Beavon, PhD, AstraZeneca (Employee, Shareholder) Karen A. Near, MD, '
'AstraZeneca (Employee, Shareholder) Kelly W. Padilla, PharmD, AstraZeneca (Employee, '
'Shareholder) Konstantina Psachoulia, PhD, AstraZeneca (Employee, Shareholder) Audrey '
'Sharbaugh, PhD, AstraZeneca (Employee, Shareholder) Katie Streicher, PhD, AstraZeneca '
'(Employee, Shareholder) Menelas N. Pangalos, PhD, AstraZeneca (Employee, Shareholder) Mark T. '
'Esser, PhD, AstraZeneca (Employee, Shareholder) Robert A. Gasser, Jr., MD, AstraZeneca '
'(Employee, Shareholder)</jats:p>\n'
' </jats:sec>',
'DOI': '10.1093/ofid/ofab466.1646',
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