eVusheld Assessment reaL wORld Effectiveness in Israel Clalit Health Services (VALOR C19 IL)

An Observational Study to Assess the Real-world Effectiveness of EVUSHELD™ (Tixagevimab/Cilgavimab) as Pre-exposure Prophylaxis Against COVID-19 Among Immunocompromised Patients in Israel

An AstraZeneca-sponsored observational, electronic healthcare record (EHR)-embedded retrospective cohort study to assess the real-world effectiveness of EVUSHELD against SARS-CoV-2 infection, COVID-19-related hospitalization, and other COVID-19 related outcomes in the total EVUSHELD eligible patient population in the Clalit Health Services in Israel.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Drug: EVUSHELD

Detailed Description

This a Phase IV observational, secondary data study to assess the effectiveness of EVUSHELD in preventing COVID-19 infection and severe outcomes using the electronic medical records from the nationwide integrated health system.

The study is designed as an AstraZeneca-sponsored observational, electronic healthcare record (EHR)-embedded retrospective cohort study to assess the real-world effectiveness of EVUSHELD against SARS-CoV-2 infection, COVID-19-related hospitalization, and other COVID-19 related outcomes in the total EVUSHELD eligible patient population in the Clalit Health Services in Israel.

• Study Type: Observational
• Enrollment (Actual): 4000

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Research Site

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All EVUSHELD PrEP-eligible patient population in the Clalit Health Services system

Description

Individuals who meet all criteria below will be included. The eligibility criteria aligns with the guidelines of the Israeli Ministry of Health

Inclusion criteria:

• Aged 12 years and older as of the date of receipt of EVUSHELD
• No record of infection or SARS-CoV- hospitalization within last 90 days prior to the index date
• Individuals who are moderate/severe immune compromised due to a medical condition or receipt of immunosuppressive medications or treatments and may mount an adequate immune response to COVID-19 vaccine:
• Hypogammaglobinemia patients regularly treated with immunoglobulins
• Patients treated with B-cell depleting therapy, including for example such anti-CD20 as rituximab, obinatuzumab, ofatumumab, veltuzumab, Y-ibritumomab tiuxetan or ocrelizumab, even without malignant disease, up to six months from treatment.
• Patients that are treated with B-cell depleting therapy (i.e. anti CD20, rituximab, Y-ibritumomab tiuxetan, veltuzumab, ofatumumab, obinatuzumab, ocrelizumab), without a malignant disease
• Bone marrow transplant (up to a year from the BMT) from outside donors, or with GVHD grades 3-4.
• Bone marrow transplant (up to a 6 months after the BMT) from self
• Patients after (CAR) T-cell therapy (chimeric antigen receptor T-cell therapy) up to 6 months from the treatment.
• Lungs transplant recipients
• Solid organ transplant recipients (who has any kind of transplant) or those who received ATG (anti thymocyte globulin) over the last 6 months
• Patients with aggressive lymphoma.
• Multiple Myeloma patients that have active disease, and on treatment at the time of study initiation.

Individuals who meet the criterion below will be excluded:

Per the current FDA EUA, individuals currently infected with SARS-CoV-2 are not eligible for EVUSHELD as PrEP. Therefore, in the main analysis, individuals who meet the following criteria will also be excluded.

Exclusion Criteria:

• With evidence of COVID 19 (i.e., a positive diagnostic test, or COVID-19 diagnosis code) in the period of 90 days before (pseudo) index date OR
• With evidence of SARS-CoV-2 infection on the (pseudo) index date or anytime within the 6-day period immediately following this date (i.e., index date to index date+6)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
EVUSHELD Arm; Individuals given EVUSHELD for pre-exposure prophylaxis	Drug: EVUSHELD; EVUSHELD (AZD 7442, Tixagévimab/Cilgavimab)
Concurrent Control Arm; Individuals eligible for EVUSHELD pre-exposure prophylaxis but did not receive Evusheld

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalisation due to COVID-19	Any record of admission to hospital that was reported to the Israeli MOH as hospitalization due to SARS-CoV-2	up to 6 months
All-cause mortality	All-cause deaths reported in the patient's record	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Documented SARS-CoV-2 Infection, COVID-19 related mortality, Severe COVID-19	SARS-CoV-2 diagnostic test (eg, PCR, nucleic acid amplification, antigen) OR medical encounter resulting in a diagnosis code for COVID-19b OR medical encounter resulting in a code for isolation due to COVID-19	6 months and 12 months
COVID-19 mortality	Any record indicating death due to COVID-19 or record of death certificate mentioning SARS-CoV-2 as cause of death.	6 months and 12 months
COVID-19-related healthcare resource utilization (HCRU)	Any record of COVID-19 hospitalisation, ICU admission, mechanical ventilation and prescriptions of therapies for COVID-19	6 months
COVID-19-related healthcare resource utilization	Any record of hospital admission including hospital lenght of stay, ICU, mechanical ventilation, prescription/dispensations of antiviral drugs used for COVID-19 drugs	6 months
SAEs/AESIs	Any record of Serious Adverse Events (SAEs) or Adverse Events of Special Interests (AESIs) up to 6 months following initiation of Evusheld	6 months
Adverse events (AEs)	Any record of Adverse events up to 12 months following initiation of Evusheld	12 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Clalit Health Services

Publications and helpful links

Helpful Links

• redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2023
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Evusheld; Immunocompromised Patients; Pre-exposure Prophylaxis Against COVID-19
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Anti-Infective Agents; Antiviral Agents; Cilgavimab and tixagevimab drug combination
• Other Study ID Numbers: D8850R00002

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 deidentified individual patient-level data in an approved sponsored tool . 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes