Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19

Study Overview
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Brief Summary
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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 II study is to evaluate the safety, neutralizing activity and efficacy of AZD3152 for pre exposure prophylaxis of COVID-19

Detailed Description
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Phase II study to assess the safety, neutralizing activity and efficacy of one dose of AZD3152 compared with one dose of placebo in adults with immunocompromised conditions, including comorbidities contributing to weakened immunity, thereby increasing the risk of COVID-19 progression up to severe grade.

Official Title
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A Phase II Randomized, Double-blind Study to Evaluate the Safety, Neutralizing Activity and Efficacy of AZD3152 for Pre-exposure Prophylaxis of COVID-19 in Participants Having an Increased Risk for Inadequate Response to Active Immunization (NOVELLA)

Conditions
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COVID-19, SARS-CoV-2

Intervention / Treatment
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* Biological: Biological: AZD3152
* Biological: Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 years of age or older at the time of signing the informed consent. Weight ≥ 45 kg at Visit 1. Participants must satisfy at least 1 of the following risk factors at enrollment: Obese, ie, BMI ≥ 30 Congestive heart failure Chronic obstructive pulmonary disease Chronic kidney disease Intolerant of vaccine Immunocompromised state (one of the following risk factors ): Have cancer Have solid organ transplant or a hematopoietic stem cell transplant Are actively taking immunosuppressive medicines Received chimeric antigen receptor T-cell therapy Within 1 year of receiving B-cell depleting therapies Have a moderate or severe primary immunodeficiency Medically stable WOCBP must not be pregnant or lactating and must use a highly effective method of contraception Exclusion Criteria: Known hypersensitivity to any component of the study intervention Previous hypersensitivity or severe adverse reaction following administration of a mAb Acute or febrile infection prior to dosing Has HIV infection Receipt of any convalescent COVID-19 plasma treatment, mAb against SARS-CoV-2 , COVID-19 vaccine within 6 months COVID-19 antiviral prophylaxis within at least 2 weeks COVID-19 case within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Interventional Model Description: This is a Phase II Randomized, Double-blind Study to Evaluate the Safety, Neutralizing Activity and Efficacy of AZD3152 for Pre-exposure Prophylaxis of COVID-19 in adult participants. Approximately 116 participants in Russia will be randomized at up to 10 study sites in a ratio of 3:1 to either AZD3152 or placebo administered IM.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single dose of Placebo IM (0.9% sodium chloride) | Biological: Biological: Placebo<br>* Single dose of Placebo IM (0.9% sodium chloride)<br>|
| Experimental: AZD3152<br>Single dose of 300 mg IM | Biological: Biological: AZD3152<br>* 300 mg single dose of AZD3152 IM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and proportion of subjects with AEs, SAEs, MAAEs, AESIs. | The safety profile will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data | up to Day 181 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titer (GMT) and geometric mean fold rise (GMFRs) | NAbs response will be evaluated based on nAbs titer to the SARS-CoV-2 emerging dominant variant(s) circulating during the course of the study | up to Day 181 | 
| incidence of a post-treatment symptomatic COVID-19 case | Incidence of a post-treatment symptomatic COVID-19 case (negative RT-PCR at baseline to positive RT-PCR or positive antigen test at any time up to 6 months AND symptoms specified in the modified WHO definition of symptomatic COVID-19). | up to Day 181 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-exposure Prophylaxis of COVID-19