A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study in Adults to Determine the Safety and Efficacy of AZD7442, a Combination Product of Two Monoclonal Antibodies (AZD8895 and AZD1061), for Pre-exposure Prophylaxis of COVID-19.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 5,197
- 试验地点
- 1
- 主要终点
- Number of Participants With First Case of SARS-CoV-2 RT-PCR-positive Symptomatic Illness
研究概览
简要总结
This study will assess the safety and efficacy of a single dose of AZD7442(× 2 IM injections) compared to placebo for the prevention of COVID-19.
详细描述
SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemic that, as of 29 September 2020, has resulted in a high death toll to date. Unlike the majority of coronaviruses that cause mild disease in humans and animals, SARS-CoV-2 can replicate in the lower respiratory tract to cause acute respiratory distress syndrome and fatal pneumonia. Effective interventions to prevent or treat COVID-19 remain limited in number and clinical experience is limited. Clinical management is limited to supportive care, consequently overwhelming resources of healthcare systems around the world. As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 S protein. The SARS-CoV-2 spike protein contains the virus's RBD, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, is expected to block infection. Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit, and decrease Fc effector function in order to decrease the potential risk of antibody-dependent enhancement of disease. AZD7442, a combination of 2 of these mAbs (AZD8895 and AZD1061), is being evaluated for administration to prevent and/or treat COVID-19. There is currently one completed and 2 ongoing Phase I studies with AZD7442.
-The Provent repeat dose open-label sub-study is initiated to assess the safety, PK and immunogenicity of repeat doses of AZD7442 in participants currently enrolled in the Provent study who may benefit from repeat dose of AZD7442.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 years of age at the time of signing the informed consent
- •Can benefit from passive immunization with antibodies
- •Medically stable
- •Negative result from point of care SARS-CoV-2 serology testing at screening
- •Contraceptive used by women of child bearing potential, condom used by men
- •Able to understand and comply with study requirements/procedures based on the assessment of the investigator
- •Sub-study Inclusion criteria which are additional to those in parent study are as follows:
- •The participant has been randomized, dosed, and is ongoing in the PROVENT parent study and is 12±2 months post first dose of blinded IMP.
- •If one or more of the following apply:
- •Immunocompromised and/or may be at increased risk for an inadequate immune response to a COVID-19 vaccine.
- •In the opinion of the Investigator, are at increased risk and would benefit from a repeat dose of AZD
- •Documented negative SARS-CoV-2 RT-PCR test collected ≤ 3 days prior to sub-study Day 1 or a negative rapid SARS-CoV-2 antigen test at screening.
排除标准
- •Significant infection or other acute illness, including fever >100°F (>37.8°C) on the day prior to or day of randomization.
- •History of laboratory-confirmed SARS-CoV-2 infection or any positive SARS-CoV-2 result based on available data at screening.
- •History of infection with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS).
- •Known history of allergy or reaction to any component of the study drug formulation.
- •Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.
- •Any prior receipt of investigational or licensed vaccine or other mAb/biologic indicated for the prevention of SARS-CoV-2 or COVID-19 or expected receipt during the period of study follow-up.
- •Bleeding disorder or prior history of significant bleeding or bruising following IM injections or venepuncture.
- •Any other significant disease, disorder, or finding. that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data.
- •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
- •Currently pregnant or breastfeeding.
- •Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization.
- •Employees of the Sponsor involved in planning, executing, supervising, or reviewing the AZD7442 program,, clinical study site staff, or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
- •In nations, states, or other jurisdictions that for legal or ethical reasons bar the enrollment of participants who lack capacity to provide their own informed consent, such subjects are excluded.
- •Sub-study Exclusion criteria are as follows:
- •Patient have received a COVID-19 vaccination ≤ 14 days before sub-study Day1 or plan to receive a COVID-19 vaccination ≤ 14 days after sub-study Day
- •(Such participants can subsequently be included in the study once they have reached >14 days after their last dose of vaccine).
- •Patient have two or more untreated cardiac risk factors or suspected unstable cardiac disease.
- •Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
研究组 & 干预措施
AZD7442
Approximately 5150 participants will be randomized in a 2:1 ratio
• Arm 1 (n=approximately 3433) will receive a single dose (× 2IM injections) of 300 mg of AZD7442
干预措施: AZD7442 (Drug)
Placebo
Approximately 5150 participants will be randomized in a 2:1 ratio
• Arm 2 (n=approximately 1717) will receive saline placebo
干预措施: Placebo (Drug)
Sub-study AZD7442 Arm 1
Approximately 500 participants will receive AZD7442 in the repeat dose sub-study.
-Sub-study Arm 1 (~ 12 month repeat dose interval): Participants who received AZD7442 300 mg IM on Day 1 of the parent study will receive a second dose of AZD7442 300mg IM on sub-study Day 1.
干预措施: AZD7442 (Drug)
Sub-study AZD7442 Arm 2
Approximately 500 participants will receive AZD7442 in the repeat dose sub-study.
-Sub-study Arm 2(~ 6 month repeat dose interval): Participants who received placebo on Day 1 of the parent study will receive their first dose of AZD7442 300mg IM on sub-study Day1 followed by a second dose on sub-study Day 183.
干预措施: AZD7442 (Drug)
Sub-study AZD7442 Arm 3
A subset of Arm 1 and Arm 2 participants who will receive additional doses of AZD7442, 600mg, at Day 183 and Day 366 of the sub-study.
干预措施: AZD7442 (Drug)
结局指标
主要结局
Number of Participants With First Case of SARS-CoV-2 RT-PCR-positive Symptomatic Illness
时间窗: 165 Days for primary analysis, 183 days for final analysis
To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19 prior to Day 183. Planned to be evaluated through Day 183, however, the number of events required for the primary endpoint was achieved 165 days after the study start date which is displayed in the primary efficacy row below. Final analysis is final data from the study based on the pre-planned 183 days of follow up for this endpoint.
AEs, SAEs, MAAEs, and AESIs Post Dose of IMP
时间窗: 457 Days, Final analysis
To assess the safety and tolerability of a single IM dose of AZD7442 compared to placebo
次要结局
- The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP(366 Days)
- The Incidence of COVID-19-related Emergency Department Visits Occurring After Dosing With IMP(366 days)
- Incidence of ADA to AZD7442 in Serum(457 days)
- The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARS-CoV-2 Nucleocapsid Antibodies.(366 days)
- Serum AZD7442 Concentrations, PK Parameters if Data Permit.(457 days)