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Trial record 1 of 5 for:    SUPERNOVA
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Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study (SUPERNOVA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05648110
Recruitment Status : Active, not recruiting
First Posted : December 13, 2022
Last Update Posted : April 17, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
COVID-19, SARS-CoV-2 Biological: AZD5156 (Parent study Sentinel Safety Cohort) Biological: Placebo (Parent study Sentinel Safety Cohort) Biological: EVUSHELD™ (Parent study Main Cohort) Biological: AZD3152 (Parent study Main Cohort) Biological: Placebo (Parent study Main Cohort) Biological: AZD3152 (Sub-study) Biological: AZD7442 - EVUSHELD™ (Sub-study) Biological: AZD7442 (EVUSHELD™) (Sub-study) Immunocompromised participants offered AZD3152 Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3882 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

D7000C00001 is a Phase I/III study (Parent study) being conducted in conjunction with a Phase II sub study that will be conducted in approximately 3706 participants (approximately 3256 in the Parent study and 450 in the sub study) to evaluate the safety, efficacy, PK, 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.

The Parent study will consist of 2 cohorts: a Sentinel Safety Cohort and a Main Cohort. The Sentinel Safety Cohort will compare AZD5156 with placebo, while the Main Cohort will compare AZD3152 with placebo.

The sub-study will have an initial Sentinel Safety Cohort that will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent with all degrees of SARS-CoV-2 infection risk. Participants will be randomized 2:1 to receive AZD3152 or AZD7442 (EVUSHELD).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: For the Sentinel Safety Cohort and Main Cohort, neither the participant nor any of the Investigators or Sponsor staff who are involved in the treatment or clinical evaluation and monitoring of the participants will be aware of the study intervention received. Since AZD5156, AZD3152, and placebo are visually distinct prior to dose preparation (due to differences in vial volumes and container closure), study intervention will be handled by an unblinded pharmacist and administered by an unblinded administrator (or designee, in accordance with local and institutional regulations) at the study site who will be independent of safety evaluations and other trial evaluations. Personnel preparing and administering study intervention may be the same individual. Syringe masking will be required in order to maintain the blind.
Primary Purpose: Prevention
Official 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
Actual Study Start Date : December 16, 2022
Actual Primary Completion Date : September 7, 2023
Estimated Study Completion Date : January 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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


Outcome Measures
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Primary Outcome Measures :
  1. Parent study - Sentinel Safety Cohort: To evaluate the safety of AZD5156 [ 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). ]
    Occurence of AEs, SAEs, MAAEs, and AESIs will be collected throughout the study

  2. Parent study - Main Cohort: To evaluate the safety of AZD3152 and EVUSHELD and/or placebo [ 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). ]
    Occurrence of AEs, SAEs, MAAEs, and AESIs will be collected throughout the study

  3. 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 [ 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. ]
    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.

  4. 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) [ 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. ]
    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.

  5. Sub-study: To evaluate the safety of AZD3152 and EVUSHELD [ Time Frame: SAEs, MAAEs, and AESIs collected throughout the study for the final analysis. ]
    Occurrence of AEs collected through 29 days after IMP administration for the primary analysis.

  6. 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 [ 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. ]
    SARS-CoV-2 nAb responses to a current VOC following AZD3152 administration vs SARS-CoV-2 nAb responses to prior variants following EVUSHELD administration.


Secondary Outcome Measures :
  1. Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics of AZD5156 (AZD1061 and AZD3152) in serum. [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361). ]
    AZD5156 (AZD1061 and AZD3152) serum concentrations at each visit.

  2. Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of maximum concentration (Cmax) of AZD5156 (AZD1061 and AZD3152) in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361) ]
    To describe maximum concentration (Cmax) for AZD5156 (AZD1061 and AZD3152).

  3. Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of time to maximum serum concentration (tmax) of AZD5156 (AZD1061 and AZD3152) in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361). ]
    To describe time to maximum serum concentration (tmax) for AZD5156 (AZD1061 and AZD3152).

  4. Parent study - Sentinel Safety Cohort: To characterize the Pharmacokinetics parameter of terminal half-life (t½) of AZD5156 (AZD1061 and AZD3152) in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361). ]
    To describe terminal half-life (t½) for AZD5156 (AZD1061 and AZD3152).

  5. 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 [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361). ]
    To describe area under the concentration-time curve at the last measured time point (AUClast) for AZD5156 (AZD1061 and AZD3152).

  6. 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 [ Time Frame: Samples will be collected from visit 1 (Day 1) up to visit 11 (Day 361). ]
    To describe area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) for AZD5156 (AZD1061 and AZD3152).

  7. Parent study - Sentinel Safety Cohort: To evaluate the ADA responses to AZD5156, AZD3152, and AZD1061 in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 11 (Day 361) ]
    Incidence of ADA to AZD5156, AZD3152, and AZD1061, ADA titers

  8. 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 [ Time Frame: Visit 3 (Day 29) ]

    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.


  9. 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 [ Time Frame: COVID-19 incidence variables to be evaluated through Visit 9 (Day 361) ]

    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)

  10. Parent study - Main Cohort: To characterize the Pharmacokinetics (PK)of the AZD3152 and AZD7442 (AZD1061 and AZD8865) in serum concentrations at each visit. [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 9 (Day 361) ]
    AZD3152 and AZD7442 (AZD1061 and AZD8895) serum concentrations at each visit.

  11. Parent study - Main Cohort: To evaluate the Anti-drug Antibodies (ADA) responses to AZD3152 and AZD7442 in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 9 (Day 361) ]
    Incidence of Anti-drug Antibodies (ADA) to AZD3152, AZD7442, AZD1061, and AZD8895, ADA titers

  12. Sub-study: To characterize the Pharmacokinetics of AZD3152 and AZD7442 (EVUSHELD) in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 5 (Day 181). ]
    AZD3152, AZD7442 (EVUSHELD), cilgavimab, and tixagevimab concentrations in serum, over time

  13. Sub-study:To evaluate the ADA response to AZD3152 and AZD7442 (EVUSHELD) in serum [ Time Frame: Samples will be collected from Visit 1 (Day 1) up to Visit 5 (Day 181). ]
    Incidence of ADA to AZD3152, AZD7442 (EVUSHELD), cilgavimab, and tixagevimab; ADA titers


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05648110


Locations
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Sponsors and Collaborators
AstraZeneca
More Information
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Additional Information:

Publications:
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.
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.
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.
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.

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05648110    
Other Study ID Numbers: D7000C00001
2022-002378-95 ( EudraCT Number )
First Posted: December 13, 2022    Key Record Dates
Last Update Posted: April 17, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Pre-exposure Prophylaxis of COVID-19
Additional relevant MeSH terms:
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COVID-19
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
 Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Cilgavimab and tixagevimab drug combination
Antiviral Agents
Anti-Infective Agents