Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study
Purpose
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
- COVID-19, SARS-CoV-2
Eligibility
- Eligible Ages
- Over 12 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
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 Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- 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).
- Primary Purpose
- Prevention
- 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.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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). |
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|
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). |
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|
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). |
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|
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). |
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|
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). |
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|
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). |
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|
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. |
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|
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. |
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|
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. |
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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. |
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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. |
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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. |
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Recruiting Locations
More Details
- NCT ID
- NCT05648110
- Status
- Active, not recruiting
- Sponsor
- AstraZeneca
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.