Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults

Study Overview
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Brief Summary
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This study will assess the efficacy of AZD7442 for the post-exposure prophylaxis of COVID-19 in Adults.

Detailed Description
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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 ongoing Phase I study with AZD7442.

Official Title
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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 Post-exposure Prophylaxis of COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: AZD7442
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age at the time of signing the informed consent Adults with potential exposure, within 8 days, to a specific identified individual with laboratory-confirmed SARS-COV-2 infection, symptomatic or asymptomatic Participants must not have had COVID-19 symptoms within 10 days of dosing Negative result from point of care SARS-CoV-2 serology test at screening Contraception used by women of childbearing potential, condom by men Able to understand and comply with study requirements/procedures based on the assessment of the investigator Exclusion Criteria: History of laboratory-confirmed SARS-CoV-2 infection or SARS-CoV-2 seropositivity 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. Clinically significant bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture. Any other significant disease, disorder, or finding that, in the judgement of the investigator, 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 breast feeding. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD7442<br>Participants will be randomized in a 2:1 ratio to receive a single dose (× 2 IM injections) of either 300 mg of AZD7442 (n = approximately 750) or saline placebo (n = approximately 375) on Day 1. | Drug: AZD7442<br>* Single dose (× 2 IM injections) of 300 mg of AZD7442 on Day 1.<br>* Other names: A combination of 2 mAbs (AZD8895 and AZD1061);|
| Placebo Comparator: Placebo<br>Participants will be randomized in a 2:1 ratio to receive a single dose (× 2 IM injections) of either 300 mg of AZD7442 (n = approximately 750) or saline placebo (n = approximately 375) on Day 1. | Drug: Placebo<br>* Single dose (× 2 IM injections) of saline placebo on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness | To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19 | Planned to be evaluated through Day 183, however, the number of participants required was achieved 127 days after the study start date | 
| AEs, SAEs, MAAEs, and AESIs Post Dose of IMP |  | 457 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP |  | 183 Days | 
| The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARSCoV- 2 Nucleocapsid Antibodies |  | 366 Days | 
| The Incidence of COVID-19-related Death Occurring After Dosing With IMP |  | 366 Days | 
| The Incidence of All-cause Mortality Occurring After Dosing With IMP |  | 366 Days | 
| Serum AZD7442 Concentrations, PK Parameters |  | 457 Days | 
| Incidence of ADA to AZD7442 in Serum |  | 457 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post exposure COVID-19