Phase III, double-blinded study using AZD7442 or Placebo for the prevention of COVID-19 disease in adults who have not been exposed to COVID-19 infection

INTERVENTION: Product Code: AZD1061 Pharmaceutical Form: Solution for injection INN or Proposed INN: AZD1061 CAS Number: 2420563‐99‐9 Current Sponsor code: AZD1061 Other descriptive name: monoclonal antibody (mAb) Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intramuscular use Product Code: AZD8895 Pharmaceutical Form: Solution for injection INN or Proposed INN: AZD8895 CAS Number: 2420564‐02‐7 Current Sponsor code: AZD8895 Other descriptive name: monoclonal antibody (mAb) Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intramuscular use CONDITION: COVID‐19 ; MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID‐19 through Day 183; ; To assess the safety and tolerability of a single IM dose of AZD7442 compared to placebo. Primary end point(s): The primary endpoint is the first case of SARS‐CoV‐2 RT‐PCR‐positive symptomatic illness occurring post dose of IMP through Day 183.; ; For safety; AEs, SAEs, MAAEs, and AESIs through 365 days post dose of IMP. Secondary Objective: Key Secondary; To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID‐19 through Day 366; ; Other Secondary ; ‐ To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of SARS‐CoV‐2 infection; ‐ To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of severe or critical symptomatic COVID‐19; ‐ To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID‐19‐related Emergency Department visits; ‐ To assess the pharmacokinetics of AZD7442 administered as a single dose of 300 mg IM; ‐To evaluate ADA responses to AZD7442 in serum Timepoint(s) of evaluation of this end point: Day 183 SECONDARY OUTCOME: Secondary end point(s): Key Secondary endpoint;; ‐The key secondary endpoint is the incidence of the first case of SARS‐CoV‐2 RT‐PCR‐positive symptomatic illness through Day 366.; ; Other Secondary endpoint;; ‐ 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.; ‐ The incidence of SARS‐CoV‐2 RT‐PCR‐positive severe or critical symptomatic illness occurring post dose.; ‐ The incidence of COVID‐19‐related Emergency Department visits occurring post dose.; ‐Serum AZD7442 concentrations.; ‐PK parameters if data permit.; ‐Incidence of ADA to AZD7442 in serum. Timepoint(s) of evaluation of this end point: Day 366 INCLUSION CRITERIA: 1. Participant must be = 18 years of age at the time of signing the informed consent. 2. Candidate for benefit from passive immunization with antibodies, defined as: (a) Increased risk for inadequate response to active immunization (predicted poor responders to vaccines), defined as; o Elderly, ie, = 60 years old o Obese, ie, BMI = 30 o Congestive heart failure o Chronic obstructive pulmonary disease o Chronic kidney disease, ie, GFR < 30 mL/min/1.73 m2 o Chronic liver disease o HIV infection o Persons with solid organ transplants o Immunosuppressive therapy o Intolerant of vaccine. Defined as previous history of severe adverse event or serious adverse event after receiving any approved vaccine (b) Increased risk for SARS‐CoV‐2 infection, defined as those whose locations or circumstances put them at appreciable risk of exposure to SARS‐CoV‐2 and COVID‐19, based on available risk assessment at time of enrollment. Examples