Parent Study: Study Understanding Pre-Exposure pRophylaxis of NOvel Anitbodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOvel Anitbodies (SUPERNOVA Sub-study) (SUPERNOVA)

A Phase I/III Randomized, Double-blind Study to Evaluate the Safety, Efficacy and Neutralizing Activity of AZD5156/AZD3152 for Pre-exposure Prophylaxis of COVID-19 in Participants With Conditions Causing Immune Impairment. Sub-study: Phase II Open Label Sub-study to Evaluate the Safety, PK, and Neutralizing Activity of AZD3152 for Pre-exposure Prophylaxis of COVID-19

AZD3152, a single mAb, is being developed to have broad neutralizing activity across known SARS-CoV-2 variants of concern for pre-exposure prophylaxis of COVID-19.

The aim of the Phase I/III study (Parent Study) will be to evaluate the safety, efficacy and neutralizing activity of AZD3152 compared with comparator for pre exposure prophylaxis of COVID-19, and separately evaluate the safety and PK of AZD5156, a combination of AZD3152 and AZD1061.

Sub-study:

This Phase II sub-study of SUPERNOVA will assess the safety, PK, and predicted neutralizing activity of AZD3152 compared with EVUSHELD for pre-exposure prophylaxis of COVID-19.

Study Overview

• Status: Completed
• Conditions: COVID-19, SARS-CoV-2
• Intervention / Treatment: Biological: AZD3152 (Sub-study); Biological: AZD7442 - EVUSHELD™ (Sub-study); Biological: AZD7442 (EVUSHELD™) (Sub-study) Immunocompromised participants offered AZD3152; Biological: AZD5156 (Parent study Sentinel Safety Cohort); Biological: Placebo (Parent study Sentinel Safety Cohort); Biological: AZD3152 (Parent study Main Cohort); Biological: EVUSHELD™ (Parent study Main Cohort); Biological: Placebo (Parent study Main Cohort)

Detailed Description

In the Parent study, the Phase I Sentinel Safety Cohort will assess the safety of AZD5156 (a combination of 2 mAbs, AZD1061 [cilgavimab, a component of AZD7442 (EVUSHELD)] and AZD3152) in healthy adults and the Phase III Main Cohort will assess the safety, efficacy, PK, and neutralizing activity of two doses of AZD3152 compared with two doses of comparator given at a 6-month interval in adults and adolescents 12 years of age or older (weighing at least 40 kg) with conditions causing immune impairment, who are less likely to mount an adequate protective immune response after vaccination and thus are at higher risk of developing severe COVID-19 in 18 countries.

Sub-study:

This Phase II sub-study of SUPERNOVA is operating in USA only, and it will assess the safety, PK, and predicted neutralizing activity of AZD3152 in adults 18 years of age or older (weighing at least 40 kg) with conditions causing immune impairment who are less likely to mount an adequate protective immune response after vaccination as well as individuals who are immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.

• Study Type: Interventional
• Enrollment (Actual): 3882
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • Research Site
  • Melbourne, Australia, 3000
    • Research Site
  • Murdoch, Australia, 6150
    • Research Site
  • Parkville, Australia, 3050
    • Research Site
  • Raymond Terrace, Australia, 4101
    • Research Site
  • Sippy Downs, Australia, 4556
    • Research Site
  • West Perth, Australia, 6005
    • Research Site
• Belgium
  • Alken, Belgium, 3570
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
    • Montreal, Quebec, Canada, H2X 0A9
      • Research Site
• Denmark
  • Aalborg, Denmark, 9100
    • Research Site
  • Aarhus, Denmark, 8200
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • Roskilde, Denmark, 4000
    • Research Site
  • Svendborg, Denmark, DK-5700
    • Research Site
• France
  • Dijon, France, 21079
    • Research Site
  • La Roche-sur-Yon, France, 85925
    • Research Site
  • Lille, France, 59037
    • Research Site
  • Nantes, France, 44093
    • Research Site
  • Nîmes, France, 30029
    • Research Site
  • Paris, France, 75014
    • Research Site
  • Paris, France, 75475
    • Research Site
  • Poitiers, France, 86000
    • Research Site
  • Saint-Etienne, France, 42055
    • Research Site
  • Strasbourg, France, 67091
    • Research Site
  • Toulouse, France, 31059
    • Research Site
  • Tours, France, 37000
    • Research Site
• Germany
  • Cologne, Germany, 50924
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Hamburg, Germany, 20095
    • Research Site
  • Hanover, Germany, 30625
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
• Israel
  • Petah Tikva, Israel, 49100
    • Research Site
  • Ramat Gan, Israel, 52621
    • Research Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuala Lumpur, Malaysia, 56000
    • Research Site
  • Kuching, Malaysia, 93586
    • Research Site
  • Seberang Jaya, Malaysia, 13700
    • Research Site
  • Sunway City, Malaysia, 47500
    • Research Site
• Poland
  • Krakow, Poland, 30-727
    • Research Site
  • Skórzewo, Poland, 60-185
    • Research Site
• Singapore
  • Singapore, Singapore, 169608
    • Research Site
  • Singapore, Singapore, 117599
    • Research Site
  • Singapore, Singapore, 308442
    • Research Site
• South Korea
  • Gyeonggi-do, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 08308
    • Research Site
  • Seoul, South Korea, 5505
    • Research Site
• Spain
  • Badalona, Spain, 08916
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Barcelona, Spain, 08041
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Madrid, Spain, 28031
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Marbella (Málaga), Spain, 29603
    • Research Site
  • Mérida, Spain, 06800
    • Research Site
  • Pozuelo de Alarcón, Spain, 28223
    • Research Site
  • Valladolid, Spain, 47003
    • Research Site
  • Vigo, Spain, 36312
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan, 11490
    • Research Site
• Thailand
  • Bangkok, Thailand, 10400
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Muang, Thailand, 11000
    • Research Site
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates, 2951
    • Research Site
  • Abu Dhabi, United Arab Emirates, 34555
    • Research Site
• United Kingdom
  • Bristol, United Kingdom, BS2 8DX
    • Research Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Research Site
  • Harrow, United Kingdom, HA1 3UJ
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Research Site
  • Liverpool, United Kingdom, L7 8XP
    • Research Site
  • London, United Kingdom, SE1 7EH
    • Research Site
  • London, United Kingdom, W1T 7HA
    • Research Site
  • Manchester, United Kingdom, M8 5RB
    • Research Site
  • Oxford, United Kingdom, OX3 7LA
    • Research Site
  • Sheffield, United Kingdom, S10 2JF
    • Research Site
  • Torpoint, United Kingdom, PL11 2TB
    • Research Site
  • Truro, United Kingdom, TR1 3LJ
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Research Site
    • Birmingham, Alabama, United States, 35215
      • Research Site
    • Mobile, Alabama, United States, 36608
      • Research Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Research Site
    • Mesa, Arizona, United States, 85206
      • Research Site
    • Mesa, Arizona, United States, 85210
      • Research Site
    • Tucson, Arizona, United States, 85712
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Research Site
  • California
    • Colton, California, United States, 92324
      • Research Site
    • La Mesa, California, United States, 91942
      • Research Site
    • Long Beach, California, United States, 90815
      • Research Site
    • Los Angeles, California, United States, 90027
      • Research Site
    • Modesto, California, United States, 95350
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
    • Tustin, California, United States, 92780
      • Research Site
    • Westminster, California, United States, 92683
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80014
      • Research Site
    • Denver, Colorado, United States, 80246
      • Research Site
    • Denver, Colorado, United States, 80209
      • Research Site
    • Fort Collins, Colorado, United States, 80525
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Research Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Fleming Island, Florida, United States, 32003
      • Research Site
    • Fort Myers, Florida, United States, 33912
      • Research Site
    • Hollywood, Florida, United States, 33024
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Lake Worth, Florida, United States, 33462
      • Research Site
    • Largo, Florida, United States, 33777
      • Research Site
    • Lauderdale Lakes, Florida, United States, 33313
      • Research Site
    • Leesburg, Florida, United States, 34748
      • Research Site
    • Medley, Florida, United States, 33166
      • Research Site
    • Miami, Florida, United States, 33126
      • Research Site
    • Miami, Florida, United States, 33186
      • Research Site
    • Miami, Florida, United States, 33125
      • Research Site
    • Miami, Florida, United States, 33135
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Miami Springs, Florida, United States, 33166
      • Research Site
    • North Miami Beach, Florida, United States, 33162
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Ormond Beach, Florida, United States, 32174
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
    • St. Petersburg, Florida, United States, 33713
      • Research Site
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site
    • Columbus, Georgia, United States, 31904
      • Research Site
  • Idaho
    • Boise, Idaho, United States, 83712
      • Research Site
  • Illinois
    • Burr Ridge, Illinois, United States, 60527
      • Research Site
    • Chicago, Illinois, United States, 60612
      • Research Site
    • Chicago, Illinois, United States, 60640
      • Research Site
    • Gurnee, Illinois, United States, 60031
      • Research Site
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Research Site
    • Evansville, Indiana, United States, 47712
      • Research Site
    • South Bend, Indiana, United States, 46617
      • Research Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Research Site
  • Kansas
    • Overland Park, Kansas, United States, 66204
      • Research Site
    • Wichita, Kansas, United States, 67214
      • Research Site
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Research Site
    • Lexington, Kentucky, United States, 40503
      • Research Site
    • Lexington, Kentucky, United States, 40509
      • Research Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Research Site
    • Metairie, Louisiana, United States, 70006
      • Research Site
    • New Orleans, Louisiana, United States, 70119
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
    • Methuen, Massachusetts, United States, 01844
      • Research Site
    • Springfield, Massachusetts, United States, 01107
      • Research Site
    • Worcester, Massachusetts, United States, 01655
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site
    • Farmington Hills, Michigan, United States, 48334
      • Research Site
    • Grand Rapids, Michigan, United States, 49525
      • Research Site
    • Novi, Michigan, United States, 48377
      • Research Site
    • Saint Clair Shores, Michigan, United States, 48081
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55446
      • Research Site
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Research Site
    • Kansas City, Missouri, United States, 64114
      • Research Site
    • St Louis, Missouri, United States, 63110
      • Research Site
    • St Louis, Missouri, United States, 63131
      • Research Site
  • Montana
    • Missoula, Montana, United States, 59808
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Research Site
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Research Site
  • New York
    • Buffalo, New York, United States, 14202
      • Research Site
    • Ridgewood, New York, United States, 11385
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
    • Rochester, New York, United States, 14607
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28208
      • Research Site
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Monroe, North Carolina, United States, 28112
      • Research Site
    • Morehead City, North Carolina, United States, 28557
      • Research Site
    • Wilmington, North Carolina, United States, 28403
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Research Site
    • Westlake, Ohio, United States, 44145
      • Research Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Research Site
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
    • Harrisburg, Pennsylvania, United States, 17110
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15232
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Research Site
    • North Charleston, South Carolina, United States, 29405
      • Research Site
    • Rock Hill, South Carolina, United States, 29732
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • El Paso, Texas, United States, 79925
      • Research Site
    • Houston, Texas, United States, 77070
      • Research Site
    • Houston, Texas, United States, 77054
      • Research Site
    • Houston, Texas, United States, 77089
      • Research Site
    • Houston, Texas, United States, 77081
      • Research Site
    • Houston, Texas, United States, 77065
      • Research Site
    • Kingwood, Texas, United States, 77339
      • Research Site
    • Mesquite, Texas, United States, 75150
      • Research Site
    • San Angelo, Texas, United States, 76904
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • Shenandoah, Texas, United States, 77384
      • Research Site
  • Utah
    • Layton, Utah, United States, 84041
      • Research Site
    • Salt Lake City, Utah, United States, 84115
      • Research Site
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Research Site
    • Norfolk, Virginia, United States, 23502
      • Research Site
    • Norfolk, Virginia, United States, 23507
      • Research Site
  • Washington
    • Olympia, Washington, United States, 98506
      • Research Site
    • Seattle, Washington, United States, 98109
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hochiminh City, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Parent study - Sentinel Safety Cohort Participants (Phase I):

Parent study - Sentinel Cohort Inclusion Criteria:

• Healthy participants according to medical history, physical examination, baseline safety laboratory tests, and screening parameters, according to the judgment of the investigator, with no concomitant disease or concomitant medication (except for medication specifically permitted by the protocol).
• Age 18 to 55 years at the time of signing the informed consent.
• Negative rapid antigen test at Visit 1.
• Weight ≥ 45 kg and ≤ 110 kg at screening.

Parent study - Sentinel Cohort Exclusion Criteria:

• Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration.
• Known hypersensitivity to any component of the study intervention.
• Previous hypersensitivity or severe adverse reaction following administration of a mAb.
• Acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the screening period or may be rescreened once.
• Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
• Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
• Receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to Visit 1.
• Previous receipt of a mAb against SARS-CoV-2.
• Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.
• Receipt of a COVID-19 antiviral for prophylaxis within 3 months prior to Visit 1
• COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing]).
• Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study.
• Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening.
• Active infection with hepatitis B or C.
• Serum creatinine, AST, or ALT above 1.5 × ULN at screening
• History of malignancy other than treated non-melanoma skin cancers or locally-treated cervical cancer in previous 5 years.

Parent study - Main Cohort Participants (Phase III):

Parent study - Main Cohort Inclusion Criteria:

• Participant must be 12 years of age or older at the time of signing the informed consent.
• Negative rapid antigen test prior to dosing at Visit 1.
• Weight ≥ 40 kg at screening.

• Participants must satisfy at least 1 of the following risk factors at enrollment:

  • Have solid tumor cancer and be on active immunosuppressive treatment
  • Have hematologic malignancy

  • Transplant participants must satisfy at least one of the following:

    1. Have had a solid organ transplant within 2 years and / or
    2. Had a hematopoietic stem cell transplant within 2 years and / or
    3. Who have chronic graft-versus-host disease
    4. Participants who previously had a solid organ transplant or hematopoietic stem cell transplant more than 2 years prior to Visit 1 may also be eligible based on the inclusion criterion for immunosuppressive treatment
  • Are actively taking immunosuppressive medicines (eg, are using corticosteroids [ie, ≥ 20 mg prednisone or equivalent per day when administered for ≥ 2 weeks], high dose alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive [eg, Bruton's tyrosine kinase inhibitors], tumor-necrosis blockers, or other immunosuppressive or immunomodulatory biologic agents (eg, for rheumatic diseases)
  • Received chimeric antigen receptor T cell therapy
  • Within 1 year of receiving B-cell depleting therapies (eg, rituximab, ocrelizumab, ofatumumab, alemtuzumab)
  • Have a moderate or severe primary (eg, DiGeorge syndrome) or secondary (eg, hemodialysis) immunodeficiency
  • Advanced or untreated HIV infection (people with HIV and CD4 cell counts < 200/mm3 within 6 months of Visit 1, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
• Medically stable defined as disease not requiring significant change in maintenance therapy or hospitalization for worsening disease or any recent CV event (eg, acute myocardial infarction, thromboembolic event) during the 1 month prior to enrollment, with no acute change in condition at the time of study enrollment as judged by the Investigator and no expected changes at the time of the enrollment.
• Able to understand and comply with all study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative or equivalent representative as locally defined), including those at Illness Visits, based on the assessment of the Investigator.

Parent study - Main Cohort Exclusion Criteria:

• Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration. Note: female participants aged > 12 years will be considered to be a woman of childbearing potential.
• Known hypersensitivity to any component of the study intervention.
• Previous hypersensitivity or severe adverse reaction following administration of a mAb.
• Acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves and may be rescreened for enrollment once.
• Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
• Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
• Receipt of IV or SC immunoglobulin within 6 months prior to Visit 1 or expected to receive IV or SC immunoglobulin 6 months after dosing.
• Receipt of convalescent COVID-19 plasma treatment within 6 months prior to Visit 1.
• Previous receipt of a mAb against SARS-CoV-2 within 6 months prior to Visit 1.
• Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.
• Receipt of a COVID-19 antiviral for prophylaxis within at least 2 weeks prior to Visit 1.
• COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing]).
• Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study except where the participant ceased IMP treatment >90 days and is in the follow-up period of the study and not expected to receive further IMP).

Sub-study - Inclusion Criteria (Phase II):

Sub-study - Sentinel Safety Cohort Inclusion Criteria:

• Healthy, defined according to medical history, physical examination, baseline safety laboratory tests, and screening parameters, according to the judgment of the Investigator.
• Participants must be 18 to 55 years at the time of signing the informed consent.
• Weight ≥ 45 kg and ≤ 110 kg at screening.

Sub-study - Full Sub-study Cohort Inclusion Criteria:

• Immunocompromised or immunocompetent, including healthy participants, with all degrees of SARS-CoV-2 infection risk, will be enrolled following completion of Sentinel Safety Cohort enrolment.
• Participants must be 18 years of age or older at the time of signing the informed consent.
• Weight ≥ 40 kg at screening.

Sub-study - Sub-study Sentinel Safety Cohort and Full Sub-study Cohort Inclusion Criteria:

• Written informed consent and any locally required authorization (eg, HIPAA in the US) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
• Negative rapid antigen test for SARS-CoV-2 prior to dosing at Visit 1.
• Medically stable defined as disease not requiring significant change in maintenance therapy or hospitalization for worsening disease or any recent cardiovascular event (eg, acute myocardial infarction, thromboembolic event) during the 1 month prior to enrollment, with no acute change in condition at the time of study enrollment as judged by the Investigator and no expected changes at the time of the enrollment.
• Able to understand and comply with all study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative or equivalent representative as locally defined), based on the assessment of the Investigator.

Sub-study - Exclusion Criteria (Phase II):

Sub-study - Sentinel Safety Cohort Exclusion Criteria:

• Active infection with hepatitis B or C.
• Serum creatinine, AST, or ALT above 1.5 × ULN at screening.
• History of malignancy other than treated non-melanoma skin cancers or locally-treated cervical cancer in previous 5 years.

Sub-study - Sentinel Safety Cohort and Full Sub-study Cohort Exclusion Criteria:

• Receipt of EVUSHELD (AZD7442) within 12 months prior to Visit 1.
• Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration. Note: female participants aged > 12 years will be considered to be a woman of childbearing potential.
• Known hypersensitivity to any component of the study intervention.
• Previous hypersensitivity or severe adverse reaction following administration of a mAb.
• Acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves and may be rescreened for enrollment once.
• Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
• Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
• Has human immunodeficiency virus infection.
• Receipt of IV or SC immunoglobulin or blood products within 6 months prior to Visit 1 and expected to receive IV or SC immunoglobulin or blood products 6 months after dosing.
• Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.
• Receipt of a COVID-19 antiviral for prophylaxis within at least 2 weeks prior to Visit 1.
• COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory RT-PCR testing or a rapid antigen test [including at-home testing]).
• Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study (except where the participant ceased IMP treatment > 90 days and is in the follow-up period of the study and not expected to receive further IMP).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parent study Sentinel Safety Cohort - Subcohort 1a Gluteal - AZD5156; The Sentinel Safety Cohort of the Parent Study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: AZD5156 (Parent study Sentinel Safety Cohort); 600 mg AZD5156 consisting of 300 mg AZD1061 at 100 mg/mL and 300 mg AZD3152 at 150 mg/mL 3 mL of AZD1061 2 mL of AZD3152 IM on Visit 1 Day 1
Placebo Comparator: Parent study Sentinel Safety Cohort - Subcohort 1a Gluteal - Placebo; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: Placebo (Parent study Sentinel Safety Cohort); single dose of Placebo (3 mL + 2 mL) IM
Experimental: Parent study Sentinel Safety Cohort - Subcohort 1b Thigh - AZD5156; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: AZD5156 (Parent study Sentinel Safety Cohort); 600 mg AZD5156 consisting of 300 mg AZD1061 at 100 mg/mL and 300 mg AZD3152 at 150 mg/mL 3 mL of AZD1061 2 mL of AZD3152 IM on Visit 1 Day 1
Placebo Comparator: Parent study Sentinel Safety Cohort - Subcohort 1b Thigh - Placebo; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: Placebo (Parent study Sentinel Safety Cohort); single dose of Placebo (3 mL + 2 mL) IM
Experimental: Parent study Sentinel Safety Cohort - Subcohort 2a Gluteal- AZD5156; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: AZD5156 (Parent study Sentinel Safety Cohort); 600 mg AZD5156 consisting of 300 mg AZD1061 at 100 mg/mL and 300 mg AZD3152 at 150 mg/mL 3 mL of AZD1061 2 mL of AZD3152 IM on Visit 1 Day 1
Placebo Comparator: Parent study Sentinel Safety Cohort - Subcohort 2a Gluteal - Placebo; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: Placebo (Parent study Sentinel Safety Cohort); single dose of Placebo (3 mL + 2 mL) IM
Experimental: Parent study Sentinel Safety Cohort - Subcohort 2b Thigh - AZD5156; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: AZD5156 (Parent study Sentinel Safety Cohort); 600 mg AZD5156 consisting of 300 mg AZD1061 at 100 mg/mL and 300 mg AZD3152 at 150 mg/mL 3 mL of AZD1061 2 mL of AZD3152 IM on Visit 1 Day 1
Placebo Comparator: Parent study Sentinel Safety Cohort - Subcohort 2b Thigh - Placebo; The Sentinel Safety Cohort of the Parent study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).	Biological: Placebo (Parent study Sentinel Safety Cohort); single dose of Placebo (3 mL + 2 mL) IM
Experimental: Parent study Main Cohort - AZD3152; The Main Cohort of the Parent study will enroll approximately 3200 participants. Dosing in the Main Cohort will be staggered, so that it starts with adult participants aged 18 years and older, with no adolescent participants dosed in the Main Cohort until safety data from Visit 2a (Day 8) and Visit 2b (Day 15) have been reviewed by the DSMB for at least 80 adult Main Cohort participants (which will include at least 40 participants who have received AZD3152). Participants in the Main Cohort will be randomized 1:1 to receive AZD3152 300 mg or comparator administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention (ie, active treatment or comparator) 6 months after Visit 1.	Biological: Placebo (Parent study Sentinel Safety Cohort); single dose of Placebo (3 mL + 2 mL) IM; Biological: AZD3152 (Parent study Main Cohort); 300 mg AZD3152 at 150 mg/mL 1 IM injection (thigh) of 2 mL of AZD3152 on Visit 1 Day 1 and on Visit 5 Day 181
Active Comparator: Parent study Main Cohort - EVUSHELD™; Participants in the Main Cohort of the Parent study will be randomized 1:1 to receive AZD3152 300 mg or comparator administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention (ie, active treatment or comparator) 6 months after Visit 1. At the request of regulatory authorities the active comparator will be changed to placebo. As the comparator is given on two occasions, this means that a participant randomized to the comparator arm may receive (a) two doses of EVUSHELD, (b) a dose of EVUSHELD and a dose of placebo, or (c) two doses of placebo.	Biological: EVUSHELD™ (Parent study Main Cohort); 600 mg EVUSHELD™/AZD7442 consisting of 300 mg AZD1061 and 300 mg AZD8895, both at 100 mg/mL 2 IM injections (thigh) of 3 mL each IM on Visit 1 Day 1 and on Visit 5 Day 181; Other Names: EVUSHELD™
Placebo Comparator: Parent study Main Cohort - Placebo; Participants in the Main Cohort of the Parent study will be randomized 1:1 to receive AZD3152 300 mg or comparator administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention (ie, active treatment or comparator) 6 months after Visit 1. At the request of regulatory authorities the active comparator will be changed to placebo. As the comparator is given on two occasions, this means that a participant randomized to the comparator arm may receive (a) two doses of EVUSHELD, (b) a dose of EVUSHELD and a dose of placebo, or (c) two doses of placebo.	Biological: Placebo (Parent study Main Cohort); Single doses of 0.9% sodium chloride 2 mL IM for injection on Visit 1 Day 1 and Visit 5 Day 181
Experimental: Sub-study - AZD3152; This sub-study will enroll approximately 450 participants, ≥ 18 years of age with a minimum weight of 40 kg. An initial Sentinel Safety Cohort will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.	Biological: AZD3152 (Sub-study); Single dose of 1200 mg IV at Visit 1 Day 1
Active Comparator: Sub-study - AZD7442 (EVUSHELD™); This sub-study will enroll approximately 450 participants, ≥ 18 years of age with a minimum weight of 40 kg. An initial Sentinel Safety Cohort will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.	Biological: AZD7442 - EVUSHELD™ (Sub-study); Single dose 300 mg IM administered on Visit 1 Day 1
Experimental: Sub-study - AZD7442 (EVUSHELD™) Immunocompromised participants offered AZD3152 1200mg IV; This sub-study will enroll approximately 450 participants, ≥ 18 years of age with a minimum weight of 40 kg. An initial Sentinel Safety Cohort will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.	Biological: AZD7442 (EVUSHELD™) (Sub-study) Immunocompromised participants offered AZD3152; Single dose of AZD7442 (EVUSHELD™) 300 mg IM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Main Cohort) Occurrence of AEs Collected Through Approximately 90 Days After Each IMP Administration; SAEs, MAAEs, and AESIs Collected Through Day 451	Primary: (Main Cohort) Occurrence of AEs collected through approximately 90 days after each IMP administration; SAEs, MAAEs, and AESIs collected through Day 451	AEs: through 90 days post each IMP administration; SAEs, MAAEs, and AESIs: through Day 451
(Sub-study) Occurrence of AEs Collected Through 29 Days After IMP Administration. SAEs, MAAEs, and AESIs Collected Through Day 451.	(Sub-study) Occurrence of AEs collected through 29 days after IMP administration. SAEs, MAAEs, and AESIs collected through Day 451 (ie, end of study).	through 29 days post IMP administration (AEs); through Day 451 (SAEs, MAAEs, and AESIs)
(Sub-study) Predicted SARS-CoV-2 nAb Titers Derived From Serum PK and in Vitro IC50 for SARS-CoV-2 Variants BA.2.86 Following AZD3152 Administration and Alpha Variant Following EVUSHELD Administration.	AZD3152 Day 29 predicted nAb titer for BA.2.86 variant = AZD3152 serum PK conc. (ng/mL)/(3.8 ng/mL), where 3.8 ng/mL is AZD3152 BA.2.86 IC50. AZD7442 Day 29 predicted nAb titer for Alpha variant = AZD7442 serum PK conc. (ng/mL)/(2.1 ng/mL), where 2.1 ng/mL is AZD7442 Alpha IC50. This table only shows AZD3152 and AZD7442 concentration at Day 29.	at Day 29
(Sub-study) Predicted SARS-CoV-2 nAb Titers Derived From Serum PK and in Vitro IC50 for SARS-CoV-2 Variants BA.2.86 Following AZD3152 Administration and Alpha Variant Following EVUSHELD Administration.	AZD3152 Day 29 predicted nAb titer for BA.2.86 variant = AZD3152 serum PK conc. (ng/mL)/(3.8 ng/mL), where 3.8 ng/mL is AZD3152 BA.2.86 IC50. AZD7442 Day 29 predicted nAb titer for Alpha variant = AZD7442 serum PK conc. (ng/mL)/(2.1 ng/mL), where 2.1 ng/mL is AZD7442 Alpha IC50. This table shows the predicted nAb titer at Day 29 (please see the previous table for AZD3152 and AZD7442 concentration at Day 29).	at Day 29
(Main Cohort) Confirmed Symptomatic COVID-19 Case	(Main Cohort) Confirmed symptomatic COVID-19 case at Primary Analysis.	at Primary Analysis: average follow-up time of 170 days
(Main Cohort) Confirmed Symptomatic COVID-19 Case Attributable to Matched Variants	(Main Cohort) Confirmed symptomatic COVID-19 case attributable to matched variants at Primary Analysis.	at Primary Analysis: average follow-up time of 170 days
(Sentinel Cohort) Occurrence of AEs, SAEs, MAAEs, and AESIs Collected Through Day 461	Primary: (Sentinel Cohort) Occurrence of AEs, SAEs, MAAEs, and AESIs collected through Day 461	through Day 461

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Sub-study) AZD3152 and EVUSHELD (ie, AZD7442) Concentrations in Serum, Over Time	Secondary: (Sub-study) AZD3152 and EVUSHELD (ie, AZD7442) concentrations in serum, over time.	Day 29, Day 91, Day 181
(Sub-study) Incidence of ADA to AZD3152 and EVUSHELD	AZD3152 recipients were tested for ADA to AZD3152; EVUSHELD recipients were tested for ADA to EVUSHELD.	through Day 181
(Sub-study) Cilgavimab and Tixagevimab Concentrations in Serum, Over Time	AZD7442 (ie EVUSHELD) is composed of cilgavimab and tixagevimab. This summary is only applicable to AZD7442 group.	Day 29, Day 91, Day 181
(Sub-study) ADA Titers	ADA titers were only available for ADA positive samples.	Day 1, Day 29, Day 91, Day 181
(Main Cohort) Symptomatic COVID-19 Case (Negative RT-PCR at Baseline to Positive at Any Time up 12 Months With All Observed Events at Final Readout) Caused by Any SARS-CoV-2 Matched Variant	(Main Cohort) Symptomatic COVID-19 case (negative RT-PCR at baseline to positive at any time up 12 months with all observed events at final readout) caused by any SARS-CoV-2 matched variant. First secondary endpoint to be tested in hierarchical testing after dual-primary endpoint efficacy was demonstrated in hierarchical testing	through Day 361
(Main Cohort) Symptomatic COVID-19 Case (Negative RT-PCR at Baseline to Positive at Any Time up to 12 Months With All Observed Events at Final Readout) Caused by Any SARS-CoV-2 Variants	Secondary: (Main Cohort) Symptomatic COVID-19 case (negative RT-PCR at baseline to positive at any time up to 12 months with all observed events at final readout) caused by any SARS-CoV-2 variants. Second secondary endpoint to be tested in hierarchical testing after dual-primary endpoint efficacy was demonstrated in hierarchical testing	through Day 361
(Main Cohort) Severe COVID-19 Caused by Any SARS-CoV-2 Variant Any Time up to 12 Months	third secondary endpoint to be tested in hierarchical testing after dual-primary endpoint efficacy was demonstrated in hierarchical testing	through Day 361
(Main Cohort) Severe COVID-19 Caused by Any SARS-CoV-2 Matched Variants at Any Time up to 12 Months	Secondary: (Main Cohort) Severe COVID-19 caused by any SARS-CoV-2 matched variants at any time up to 12 months through Day 361.	through Day 361
(Main Cohort) Composite of COVID-19-related Hospitalization and/or COVID-19-related Death (WHO COVID-19 Clinical Progression Scale Score ≥ 4) Any Time up to 12 Months	Secondary: (Main Cohort) Composite of COVID-19-related hospitalization and/or COVID-19-related death (WHO COVID-19 Clinical Progression Scale score ≥ 4) any time up to 12 months.	through Day 361
(Main Cohort) COVID-19-related Hospitalization Any Time up to 12 Months	Secondary: (Main Cohort) COVID-19-related hospitalization any time up to 12 months.	through Day 361
(Main Cohort) COVID-19 Related Death	(Main Cohort) COVID-19 related death - through Day 361	through Day 361
(Main Cohort) GMT of SARS-CoV-2 nAbs at Baseline and Day 29	Secondary: (Main Cohort) GMT of SARS-CoV-2 nAbs at baseline and Day 29	at Day 29
(Main Cohort) GMFR of SARS-CoV-2 nAbs at Day 29	Secondary: (Main Cohort) GMFR of SARS-CoV-2 nAbs at Day 29	at Day 29
(Main Cohort) AZD3152 and AZD7442 (EVUSHELD) Concentrations Over Time	(Main Cohort) AZD3152 and AZD7442 (EVUSHELD) concentrations over time - through Day 361	through Day 361
(Main Cohort) Incidence of ADA to AZD3152 and AZD7442 (EVUSHELD)	AZD3152 recipients were tested for ADA to AZD3152; AZD7442 recipients were tested for ADA to AZD7442.	through Day 361
(Sentinel Cohort) AZD5156, AZD1061, and AZD3152 Concentrations Over Time	AZD5156 is a combination of AZD3152 and AZD1061. This summary is only eligible for AZD5156 group.	Day 29, Day 181, Day 361
(Sentinel Cohort) Incidence of ADA to AZD5156, AZD3152, and AZD1061	(Sentinel Cohort) Incidence of ADA to AZD5156, AZD3152, and AZD1061 - through Day 361	through Day 361
(Main Cohort) ADA Titers	ADA titers were only available for ADA positive samples.	through Day 361
(Main Cohort) AZD1061 and AZD8895 Concentrations Over Time	AZD7442 (ie EVUSHELD) is composed of AZD1061 (ie, cilgavimab) and AZD8895 (ie, tixagevimab). This summary is only applicable to AZD7442 group.	through Day 361

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

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• Oganesyan V, Gao C, Shirinian L, Wu H, Dall'Acqua WF. Structural characterization of a human Fc fragment engineered for lack of effector functions. Acta Crystallogr D Biol Crystallogr. 2008 Jun;64(Pt 6):700-4. doi: 10.1107/S0907444908007877. Epub 2008 May 14.
• Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. doi: 10.1016/j.jaci.2005.12.1303.
• Alhumaid S, Al Mutair A, Al Alawi Z, Rabaan AA, Tirupathi R, Alomari MA, Alshakhes AS, Alshawi AM, Ahmed GY, Almusabeh HM, Alghareeb TT, Alghuwainem AA, Alsulaiman ZA, Alabdulmuhsin MA, AlBuwaidi EA, Dukhi AKB, Mufti HN, Al-Qahtani M, Dhama K, Al-Tawfiq JA, Al-Omari A. Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis. Allergy Asthma Clin Immunol. 2021 Oct 16;17(1):109. doi: 10.1186/s13223-021-00613-7.
• Bosch BJ, van der Zee R, de Haan CA, Rottier PJ. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J Virol. 2003 Aug;77(16):8801-11. doi: 10.1128/jvi.77.16.8801-8811.2003.
• CDC 2021 CDC (Centers for Disease Control and Prevention). General Best Practice Guidelines for Immunization: Altered Immunocompetence. Available from: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html. Accessed 23 May 2022.
• Case JB, Mackin S, Errico JM, Chong Z, Madden EA, Whitener B, Guarino B, Schmid MA, Rosenthal K, Ren K, Dang HV, Snell G, Jung A, Droit L, Handley SA, Halfmann PJ, Kawaoka Y, Crowe JE Jr, Fremont DH, Virgin HW, Loo YM, Esser MT, Purcell LA, Corti D, Diamond MS. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Nat Commun. 2022 Jul 2;13(1):3824. doi: 10.1038/s41467-022-31615-7.
• Dall'Acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem. 2006 Aug 18;281(33):23514-24. doi: 10.1074/jbc.M604292200. Epub 2006 Jun 21.
• Fact Sheet EUA Bebtelovimab 2022 US Food and Drug Administration. Fact Sheet For Healthcare Providers: Emergency Use Authorization for Bebtelovimab, March 2022. Available at: https://www.fda.gov/media/156152/download. Accessed 23 May 2022.
• Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Hebner CM, Sager J, Mogalian E, Tipple C, Peppercorn A, Alexander E, Pang PS, Free A, Brinson C, Aldinger M, Shapiro AE; COMET-ICE Investigators. Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab. N Engl J Med. 2021 Nov 18;385(21):1941-1950. doi: 10.1056/NEJMoa2107934. Epub 2021 Oct 27.
• Harpaz R, Dahl RM, Dooling KL. Prevalence of Immunosuppression Among US Adults, 2013. JAMA. 2016 Dec 20;316(23):2547-2548. doi: 10.1001/jama.2016.16477. No abstract available.
• Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, Yuan Y, Seegobin S, Ellery A, Levinson DJ, Ambery P, Arends RH, Beavon R, Dey K, Garbes P, Kelly EJ, Koh GCKW, Near KA, Padilla KW, Psachoulia K, Sharbaugh A, Streicher K, Pangalos MN, Esser MT; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Jun 9;386(23):2188-2200. doi: 10.1056/NEJMoa2116620. Epub 2022 Apr 20.
• Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016 Sep 29;3(1):237-261. doi: 10.1146/annurev-virology-110615-042301. Epub 2016 Aug 25.
• Loo YM, McTamney PM, Arends RH, Abram ME, Aksyuk AA, Diallo S, Flores DJ, Kelly EJ, Ren K, Roque R, Rosenthal K, Streicher K, Tuffy KM, Bond NJ, Cornwell O, Bouquet J, Cheng LI, Dunyak J, Huang Y, Rosenbaum AI, Pilla Reddy V, Andersen H, Carnahan RH, Crowe JE Jr, Kuehne AI, Herbert AS, Dye JM, Bright H, Kallewaard NL, Pangalos MN, Esser MT. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med. 2022 Mar 9;14(635):eabl8124. doi: 10.1126/scitranslmed.abl8124. Epub 2022 Mar 9.
• Lusvarghi S, Pollett SD, Neerukonda SN, Wang W, Wang R, Vassell R, Epsi NJ, Fries AC, Agan BK, Lindholm DA, Colombo CJ, Mody R, Ewers EC, Lalani T, Ganesan A, Goguet E, Hollis-Perry M, Coggins SA, Simons MP, Katzelnick LC, Wang G, Tribble DR, Bentley L, Eakin AE, Broder CC, Erlandson KJ, Laing ED, Burgess TH, Mitre E, Weiss CD. SARS-CoV-2 BA.1 variant is neutralized by vaccine booster-elicited serum but evades most convalescent serum and therapeutic antibodies. Sci Transl Med. 2022 May 18;14(645):eabn8543. doi: 10.1126/scitranslmed.abn8543. Epub 2022 May 18.
• Maltezou HC, Anastassopoulou C, Hatziantoniou S, Poland GA, Tsakris A. Anaphylaxis rates associated with COVID-19 vaccines are comparable to those of other vaccines. Vaccine. 2022 Jan 21;40(2):183-186. doi: 10.1016/j.vaccine.2021.11.066. Epub 2021 Nov 27.
• NIH 2017 NIH. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Available at: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. Published 2017. Accessed 23 May 2022.
• Parker EPK, Desai S, Marti M, Nohynek H, Kaslow DC, Kochhar S, O'Brien KL, Hombach J, Wilder-Smith A. Response to additional COVID-19 vaccine doses in people who are immunocompromised: a rapid review. Lancet Glob Health. 2022 Mar;10(3):e326-e328. doi: 10.1016/S2214-109X(21)00593-3. No abstract available.
• Walls AC, Tortorici MA, Snijder J, Xiong X, Bosch BJ, Rey FA, Veesler D. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11157-11162. doi: 10.1073/pnas.1708727114. Epub 2017 Oct 3.
• Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17.
• Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, Zhou D, Ginn HM, Selvaraj M, Liu C, Mentzer AJ, Supasa P, Duyvesteyn HME, Das R, Skelly D, Ritter TG, Amini A, Bibi S, Adele S, Johnson SA, Constantinides B, Webster H, Temperton N, Klenerman P, Barnes E, Dunachie SJ, Crook D, Pollard AJ, Lambe T, Goulder P, Paterson NG, Williams MA, Hall DR; OPTIC Consortium; ISARIC4C Consortium; Fry EE, Huo J, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell. 2022 Jul 7;185(14):2422-2433.e13. doi: 10.1016/j.cell.2022.06.005. Epub 2022 Jun 9.
• WHO 2022 World Health Organization. WHO COVID-19 Case definition, July 2022. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Surveillance_Case_Definition 2022.1. Accessed 05 May 2023.
• WHO 2023 WHO Coronavirus disease (COVID-19) dashboard. Available at: https://covid19.who.int. Accessed 05 June 2023.
• Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, Lum EN, Moss-Vazquez TA, Andino R, Wong JK, Byers A, Bravata DM, Tien PC, Keyhani S. Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines. JAMA. 2022 Oct 11;328(14):1427-1437. doi: 10.1001/jama.2022.17985.
• Haidar G, Thomas S, Loubet P, Baker RI, Benfield T, Boonyaratanakornkit J, Kiertiburanakul S, Kim AHJ, Longbrake EE, Molina JM, Paredes R, Tucker D, Uriel A, Weinmann-Menke J, Aksyuk AA, Clegg LE, Currie A, Yang H, Flyrin K, Gibbs M, Shroff M, Perez JL, Chang LJ, Cohen TS; SUPERNOVA study group. Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial. Lancet Infect Dis. 2025 Jul;25(7):813-826. doi: 10.1016/S1473-3099(24)00804-1. Epub 2025 Feb 24.
• Cai Y, Diallo S, Rosenthal K, Ren K, Flores DJ, Dippel A, Oganesyan V, van Dyk N, Chen X, Cantu E, Choudhary R, Sulikowski M, Adissu H, Chawla B, Kar S, Liu C, Dijokaite-Guraliuc A, Mongkolsapaya J, Rajan S, Loo YM, Beavon R, Webber C, Chang LJ, Thomas S, Clegg L, Zhang H, Screaton GR, Philbin N, Harre M, Selim A, Martinez-Alier N, Uriel A, Cohen TS, Perez JL, Esser MT, Blair W, Francica JR. AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults. Sci Transl Med. 2024 Jun 26;16(753):eado2817. doi: 10.1126/scitranslmed.ado2817. Epub 2024 Jun 26.

Helpful Links

• This webpage was designed to connect immunocompromised patients with the nearest SUPERNOVA clinical trial site.
• Redacted CSR_Main Cohort
• Redacted CSR Synopsis_Substudy
• Redacted CSR Synopsis_Sentinel Cohort
• Redacted CSP
• Redacted SAP

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2022
• Primary Completion (Actual): March 29, 2024
• Study Completion (Actual): February 11, 2025

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 13, 2022

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pre-exposure Prophylaxis of COVID-19
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Anti-Infective Agents; Antiviral Agents; cilgavimab and tixagevimab drug combination
• Other Study ID Numbers: D7000C00001; 2022-002378-95 (EudraCT Number); 2024-512554-15-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No