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

AstraZeneca216 个研究点分布在 2 个国家目标入组 3,882 人开始时间: 2022年12月16日最近更新: 2026年6月18日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: AstraZeneca
入组人数: 3,882
试验地点: 216
主要终点: Parent study - Main Cohort: To evaluate the safety of AZD3152 and EVUSHELD and/or placebo

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Prevention
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

盲法说明

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.

入排标准

年龄范围: 12 Years 至 130 Years（Child, Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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
•Weight ≥ 45 kg and ≤ 110 kg at screening.
•Parent study - Sentinel Cohort

排除标准

•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
•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
•Previous receipt of a mAb against SARS-CoV-
•Receipt of a COVID-19 vaccine within 3 months prior to Visit
•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
•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:
•Have had a solid organ transplant within 2 years and / or
•Had a hematopoietic stem cell transplant within 2 years and / or
•Who have chronic graft-versus-host disease
•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
•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
•Previous receipt of a mAb against SARS-CoV-2 within 6 months prior to Visit
•Receipt of a COVID-19 vaccine within 3 months prior to Visit
•Receipt of a COVID-19 antiviral for prophylaxis within at least 2 weeks prior to Visit
•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).
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研究组 & 干预措施

Parent study Sentinel Safety Cohort - Subcohort 1a Gluteal - AZD5156

Experimental

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).

干预措施: AZD5156 (Parent study Sentinel Safety Cohort) (Biological)

Parent study Sentinel Safety Cohort - Subcohort 1a Gluteal - Placebo

Placebo Comparator

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).