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.
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
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
3,882
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
single dose of Placebo (3 mL + 2 mL) IM
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
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
Single doses of 0.9% sodium chloride 2 mL IM for injection on Visit 1 Day 1 and Visit 5 Day 181
Single dose of 1200 mg IV at Visit 1 Day 1
Single dose 300 mg IM administered on Visit 1 Day 1
Single dose of AZD7442 (EVUSHELD™) 300 mg IM
Research Site
Birmingham, Alabama, United States
Research Site
Birmingham, Alabama, United States
Research Site
Mobile, Alabama, United States
Research Site
Glendale, Arizona, United States
Research Site
Mesa, Arizona, United States
Research Site
Parent study - Sentinel Safety Cohort: To evaluate the safety of AZD5156
Occurence of AEs, SAEs, MAAEs, and AESIs will be collected throughout the study
Time frame: 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).
Parent study - Main Cohort: To evaluate the safety of AZD3152 and EVUSHELD and/or placebo
Occurrence of AEs, SAEs, MAAEs, and AESIs will be collected throughout the study
Time frame: 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).
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
Endpoint: Confirmed symptomatic COVID-19 case, classified as a binary outcome incorporating the time from the first dose of IMP until a participant develops their first symptoms for COVID-19 or are censored. Summary measure: Prophylactic efficacy, calculated as 1 - Hazard Ratio (HR) (AZD3152 versus EVUSHELD and/or placebo) using a hazard regression model.
Time frame: 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.
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)
Endpoint: Confirmed symptomatic COVID-19 case attributable to matched variants, classified as a binary outcome incorporating the time from the first dose of IMP until a participant develops their first symptoms for COVID-19 or are censored. Summary measure: Prophylactic efficacy, calculated as 1 - Hazard Ratio (HR) (AZD3152 versus EVUSHELD and/or placebo) using a hazard regression model.
Time frame: 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.
Sub-study: To evaluate the safety of AZD3152 and EVUSHELD
Occurrence of AEs collected through 29 days after IMP administration for the primary analysis.
Time frame: SAEs, MAAEs, and AESIs collected throughout the study for the final analysis.
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
SARS-CoV-2 nAb responses to a current VOC following AZD3152 administration vs SARS-CoV-2 nAb responses to prior variants following EVUSHELD administration.
Time frame: 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.
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics of AZD5156 (AZD1061 and AZD3152) in serum.
AZD5156 (AZD1061 and AZD3152) serum concentrations at each visit.
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of maximum concentration (Cmax) of AZD5156 (AZD1061 and AZD3152) in serum
To describe maximum concentration (Cmax) for AZD5156 (AZD1061 and AZD3152).
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361)
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of time to maximum serum concentration (tmax) of AZD5156 (AZD1061 and AZD3152) in serum
To describe time to maximum serum concentration (tmax) for AZD5156 (AZD1061 and AZD3152).
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of terminal half-life (t½) of AZD5156 (AZD1061 and AZD3152) in serum
To describe terminal half-life (t½) for AZD5156 (AZD1061 and AZD3152).
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
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
To describe area under the concentration-time curve at the last measured time point (AUClast) for AZD5156 (AZD1061 and AZD3152).
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361).
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
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Mesa, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
Little Rock, Arkansas, United States
Research Site
Colton, California, United States
Research Site
La Mesa, California, United States
...and 205 more locations
To describe area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) for AZD5156 (AZD1061 and AZD3152).
Time frame: Samples will be collected from visit 1 (Day 1) up to visit 11 (Day 361).
Parent study - Sentinel Safety Cohort: To evaluate the ADA responses to AZD5156, AZD3152, and AZD1061 in serum
Incidence of ADA to AZD5156, AZD3152, and AZD1061, ADA titers
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361)
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
GMT and GMFR ratio of SARS-CoV-2 nAbs between the treatment arms at Visit 3 (Day 29). Descriptive statistics for GMTs and GMFRs will be provided.
Time frame: Visit 3 (Day 29)
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
Incidence of a post-treatment: * Symptomatic COVID-19 case (negative RT-PCR at baseline to positive at any time up to 6 and 12 months) caused by any SARS-CoV-2 variant * Symptomatic COVID-19 case (negative RT-PCR at baseline to positive at any time up to 6 and 12 months) caused by any SARS-CoV-2 matched variants * Severe COVID-19 caused by any SARS-CoV-2 variant * Severe COVID-19 caused by any SARS-CoV-2 matched variants * Composite of COVID-19 related hospitalization and/or COVID-19 related death (WHO COVID-19 Clinical Progression Scale score ≥ 4) * COVID-19 related hospitalization (separately) * COVID-19 related death (separately)
Time frame: COVID-19 incidence variables to be evaluated through Visit 9 (Day 361)
Parent study - Main Cohort: To characterize the Pharmacokinetics (PK)of the AZD3152 and AZD7442 (AZD1061 and AZD8865) in serum concentrations at each visit.
AZD3152 and AZD7442 (AZD1061 and AZD8895) serum concentrations at each visit.
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 9 (Day 361)
Parent study - Main Cohort: To evaluate the Anti-drug Antibodies (ADA) responses to AZD3152 and AZD7442 in serum
Incidence of Anti-drug Antibodies (ADA) to AZD3152, AZD7442, AZD1061, and AZD8895, ADA titers
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 9 (Day 361)
Sub-study: To characterize the Pharmacokinetics of AZD3152 and AZD7442 (EVUSHELD) in serum
AZD3152, AZD7442 (EVUSHELD), cilgavimab, and tixagevimab concentrations in serum, over time
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 5 (Day 181).
Sub-study:To evaluate the ADA response to AZD3152 and AZD7442 (EVUSHELD) in serum
Incidence of ADA to AZD3152, AZD7442 (EVUSHELD), cilgavimab, and tixagevimab; ADA titers
Time frame: Samples will be collected from Visit 1 (Day 1) up to Visit 5 (Day 181).