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 (NOVELLA)

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19, SARS-CoV-2
• Intervention / Treatment: Biological: Biological: Placebo; Biological: Biological: AZD3152

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 115522
    • Research Site
  • Moscow, Russian Federation, 125284
    • Research Site
  • Moscow, Russian Federation, 123182
    • Research Site
  • Moscow, Russian Federation, 142770
    • Research Site
  • St Petersburg, Russian Federation, 197341
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

  1. Obese, ie, BMI ≥ 30
  2. Congestive heart failure
  3. Chronic obstructive pulmonary disease
  4. Chronic kidney disease
  5. Intolerant of vaccine

  6. Immunocompromised state (one of the following risk factors ):

     1. Have cancer
     2. Have solid organ transplant or a hematopoietic stem cell transplant
     3. Are actively taking immunosuppressive medicines
     4. Received chimeric antigen receptor T-cell therapy
     5. Within 1 year of receiving B-cell depleting therapies
     6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single dose of Placebo IM (0.9% sodium chloride)	Biological: Biological: Placebo; Single dose of Placebo IM (0.9% sodium chloride)
Experimental: AZD3152; Single dose of 300 mg IM	Biological: Biological: AZD3152; 300 mg single dose of AZD3152 IM

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of COVID-19 related hospitalization, and COVID-19 related death	The number and proportion of subjects diagnosed with COVID-19 with following events: Composite number of COVID-19 related hospitalization and/or COVID-19 related death (WHO COVID-19 Clinical Progression Scale score ≥ 4); Number of COVID-19 related hospitalization (separately); Number of COVID-19 related death (separately)	up to 181 Day
Incidence and percent of subjects with post treatment sero-response for SARS-CoV-2 nucleocapsid antibodies	Occurrence of post-treatment seroresponse (negative at baseline to positive at any time post-baseline up to 6 months) for SARS-CoV-2 nucleocapsid antibodies.	up to 181 Day

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 2024

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pre-exposure Prophylaxis of COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: AZ-RU-00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.Yes,indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. All the data will be provided in blinded manner until final unblinded data analysis will be completed. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No