Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study - SUPERNOVA

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:
• o Have solid tumor cancer and be on active immunosuppressive treatment
• o Have hematologic malignancy
• o 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
• o 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)
• o Received chimeric antigen receptor T cell therapy
• o Within 1 year of receiving B-cell depleting therapies (eg, rituximab, ocrelizumab, ofatumumab, alemtuzumab)
• o Have a moderate or severe primary (eg, DiGeorge syndrome) or secondary (eg, hemodialysis) immunodeficiency
• o 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).