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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05648110




Registration number
NCT05648110
Ethics application status
Date submitted
30/11/2022
Date registered
13/12/2022

Titles & IDs
Public title
Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study
Scientific title
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
Secondary ID [1] 0 0
2024-512554-15-00
Secondary ID [2] 0 0
D7000C00001
Universal Trial Number (UTN)
Trial acronym
SUPERNOVA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19, SARS-CoV-2 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - AZD5156 (Parent study Sentinel Safety Cohort)
Treatment: Other - Placebo (Parent study Sentinel Safety Cohort)
Treatment: Other - EVUSHELD™ (Parent study Main Cohort)
Treatment: Other - AZD3152 (Parent study Main Cohort)
Treatment: Other - Placebo (Parent study Main Cohort)
Treatment: Other - AZD3152 (Sub-study)
Treatment: Other - AZD7442 - EVUSHELD™ (Sub-study)
Treatment: Other - AZD7442 (EVUSHELD™) (Sub-study) Immunocompromised participants offered AZD3152

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).

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).

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).

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.


Treatment: Other: 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

Treatment: Other: Placebo (Parent study Sentinel Safety Cohort)
single dose of Placebo (3 mL + 2 mL) IM

Treatment: Other: 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

Treatment: Other: 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

Treatment: Other: 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

Treatment: Other: AZD3152 (Sub-study)
Single dose of 1200 mg IV at Visit 1 Day 1

Treatment: Other: AZD7442 - EVUSHELD™ (Sub-study)
Single dose 300 mg IM administered on Visit 1 Day 1

Treatment: Other: AZD7442 (EVUSHELD™) (Sub-study) Immunocompromised participants offered AZD3152
Single dose of AZD7442 (EVUSHELD™) 300 mg IM
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parent study - Sentinel Safety Cohort: To evaluate the safety of AZD5156
Timepoint [1] 0 0
AEs will be collected from IMP administration approximately 90 days following. AESIs will be collected from IMP administration through to Visit 11 (Day 361). SAEs and MAAEs will be collected up to Visit 11 (Day 361).
Primary outcome [2] 0 0
Parent study - Main Cohort: To evaluate the safety of AZD3152 and EVUSHELD and/or placebo
Timepoint [2] 0 0
Occurrence of AEs collected through approximately 90 days after each IMP administration through to Visit 10 (Day 451). SAEs and MAAEs will be collected up to Visit 10 (Day 451).
Primary outcome [3] 0 0
Parent study-Main cohort: To compare the efficacy of AZD3152 to EVUSHELD and/or placebo in the prevention of symptomatic COVID 19 caused by any SARS-CoV-2 variant
Timepoint [3] 0 0
Confirmed symptomatic COVID-19 case is evaluated from first dose up to 181 days after last dose. For participants that receive two doses, the evaluation period would be approximately 361 days.
Primary outcome [4] 0 0
Parent study - Main cohort: To compare the efficacy of AZD3152 to EVUSHELD and/or placebo in the prevention of symptomatic COVID 19 attributable to matched variants (variants that do not contain the F456L mutation)
Timepoint [4] 0 0
Confirmed symptomatic COVID-19 case is evaluated from first dose up to 181 days after last dose. For participants that receive two doses, the evaluation period would be approximately 361 days.
Primary outcome [5] 0 0
Sub-study: To evaluate the safety of AZD3152 and EVUSHELD
Timepoint [5] 0 0
SAEs, MAAEs, and AESIs collected throughout the study for the final analysis.
Primary outcome [6] 0 0
Sub-study: To compare the SARS-CoV-2 nAb responses to a current VOC following AZD3152 administration vs SARS-CoV-2 nAb responses to prior variants following EVUSHELD administration
Timepoint [6] 0 0
Predicted GMT ratio of SARS-CoV-2 nAbs between the treatment arms at Visit 3 (Day 29) for the variant that each IMP is intended to neutralize.
Secondary outcome [1] 0 0
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics of AZD5156 (AZD1061 and AZD3152) in serum.
Timepoint [1] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
Secondary outcome [2] 0 0
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of maximum concentration (Cmax) of AZD5156 (AZD1061 and AZD3152) in serum
Timepoint [2] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361)
Secondary outcome [3] 0 0
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of time to maximum serum concentration (tmax) of AZD5156 (AZD1061 and AZD3152) in serum
Timepoint [3] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
Secondary outcome [4] 0 0
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of terminal half-life (t½) of AZD5156 (AZD1061 and AZD3152) in serum
Timepoint [4] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
Secondary outcome [5] 0 0
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of area under the concentration-time curve at the last measured time point (AUClast) of AZD5156 (AZD1061 and AZD3152) in serum
Timepoint [5] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
Secondary outcome [6] 0 0
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) of AZD5156 (AZD1061 and AZD3152) in serum
Timepoint [6] 0 0
Samples will be collected from visit 1 (Day 1) up to visit 11 (Day 361).
Secondary outcome [7] 0 0
Parent study - Sentinel Safety Cohort: To evaluate the ADA responses to AZD5156, AZD3152, and AZD1061 in serum
Timepoint [7] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361)
Secondary outcome [8] 0 0
Parent study - Main Cohort: To compare the nAb responses to the SARS-CoV-2 variants Alpha, Omicron BA.2, Omicron BA.4/5 and/or Omicron XBB.1.5 in serum following AZD3152 and EVUSHELD and/or placebo administration
Timepoint [8] 0 0
Visit 3 (Day 29)
Secondary outcome [9] 0 0
Parent study - Main Cohort: To describe the incidence of symptomatic COVID-19, severe COVID-19, COVID-19 related hospitalization, and COVID-19 related death in participants receiving study intervention
Timepoint [9] 0 0
COVID-19 incidence variables to be evaluated through Visit 9 (Day 361)
Secondary outcome [10] 0 0
Parent study - Main Cohort: To characterize the Pharmacokinetics (PK)of the AZD3152 and AZD7442 (AZD1061 and AZD8865) in serum concentrations at each visit.
Timepoint [10] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 9 (Day 361)
Secondary outcome [11] 0 0
Parent study - Main Cohort: To evaluate the Anti-drug Antibodies (ADA) responses to AZD3152 and AZD7442 in serum
Timepoint [11] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 9 (Day 361)
Secondary outcome [12] 0 0
Sub-study: To characterize the Pharmacokinetics of AZD3152 and AZD7442 (EVUSHELD) in serum
Timepoint [12] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 5 (Day 181).
Secondary outcome [13] 0 0
Sub-study:To evaluate the ADA response to AZD3152 and AZD7442 (EVUSHELD) in serum
Timepoint [13] 0 0
Samples will be collected from Visit 1 (Day 1) up to Visit 5 (Day 181).

Eligibility
Key inclusion criteria
Parent study - Sentinel Safety Cohort Participants (Phase I):

Parent study - Sentinel Cohort

* 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
Minimum age
12 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

* 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

* 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

* 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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/02/2025
Actual
Sample size
Target
Accrual to date
Final
3882
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment hospital [2] 0 0
Research Site - Murdoch
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment hospital [4] 0 0
Research Site - Raymond Terrace
Recruitment hospital [5] 0 0
Research Site - Sippy Downs
Recruitment hospital [6] 0 0
Research Site - West Perth
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
4101 - Raymond Terrace
Recruitment postcode(s) [6] 0 0
4556 - Sippy Downs
Recruitment postcode(s) [7] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Idaho
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kansas
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maryland
Country [18] 0 0
United States of America
State/province [18] 0 0
Massachusetts
Country [19] 0 0
United States of America
State/province [19] 0 0
Michigan
Country [20] 0 0
United States of America
State/province [20] 0 0
Minnesota
Country [21] 0 0
United States of America
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Hochiminh city

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05648110