REAl LIfe" Observational Study on the Effectiveness of Evusheld Prophylaxis Against SARS-CoV-2 Omicron Variants in Vaccine Non-responder Immunocompromised Patients

March 11, 2026 updated by: Alba Muzzi, Fondazione IRCCS Policlinico San Matteo di Pavia

REAl LIfe" Observational Study on the Effectiveness of Evusheld Prophylaxis Against SARS-CoV-2 Omicron Variants in Vaccine Non-responder Immunocompromised Patients (REALISE)

A weak immune response to two doses of vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised patients, including solid organ transplant recipients (SOTRs)1,2,3. Studies focused on third dose in SOTRs revealed that the percentage of responders increased even if a large portion of patients remained at risk for COVID-194. More in detail, the humoral response to three doses of vaccine at 1 month after the third dose in SOTRs ranged from ≈50 to ≈70% of patients5,6,7. Therefore at least a third of the patients who have an impaired immune response remain unprotected despite the administration of three doses of anti-SARS-CoV-2 vaccine8,9. Similar data emerged from studies conducted on other categories of immunosuppressed patients: less than 40% of onco-haematological patients develop antibodies after administration of two doses of vaccine and only a quarter of non-responders retrieve a humoral response after the third dose10,11. Likewise, rheumatological diseases induce a known frequent immune dysregulation that compromises an adequate response to the anti-SARS-CoV-2 vaccine12. Additionally, the emergence of the new Omicron variant has posed new issues in terms of vaccine immunogenicity. It has been observed that three doses of vaccine lead to a lower neutralization response against Omicron variant than respect to the other variants (Delta, Wild type), especially in transplanted patients13. The use of monoclonal antibodies in prophylaxis may represent a valuable choice for non-responder subjects after complete vaccination in order to prevent severe COVID-19. In this regard, recent data showed that the long-acting monoclonal antibodies (LAABs) were able to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease14. Evusheld (AZD7442) is a combination of two LAABs- Tixagevimab and Cilgavimab- derived from B-cells donated by convalescent patients after SARS-CoV-2 virus. These human monoclonal antibodies were optimized with half-life extension and reduced Fc receptor and complement C1q binding. The half-life extension more than triples the durability of its action compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration15,16. The reduced Fc receptor binding aims to minimize the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection or disease. Data on the safety and efficacy of Evusheld administered in the context of pre-exposure prophylaxis of Covid-19 can be obtained from the Provent trial that represents the largest study to date conducted in the world setting. PROVENT is a Phase III, randomized, double-blind, placebo-controlled, multi-center trial assessing the efficacy and safety of a single 300mg dose of AZD7442 compared to placebo for the prevention of COVID-19. The trial was conducted in 87 sites in the US, UK, Spain, France and Belgium. 5.197 participants were randomized in a 2:1 ratio to receive a single intramuscular (IM) dose of either 300mg of AZD7442 (n = 3460) or saline placebo (n = 1,737), administered in two separate, sequential IM injections. More than 75% had baseline co-morbidities and other characteristics that are associated with an increased risk for severe COVID-19 should they become infected, including those with immunosuppressive disease or taking immunosuppressive medications. In the Phase III PROVENT trial, Evusheld seems to reduce the risk of developing symptomatic COVID-19 by 77%, (95% confidence interval (CI): 46, 90) compared to placebo with high neutralizing antibody titers for at least six months, although further studies will be needed (AstraZeneca news release. New analyses of two AZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-term prevention17. There were no cases of severe COVID-19 or COVID-19-related deaths in those treated with AZD7442. In the placebo arm, there were three cases of severe COVID-19, which included two deaths. The monoclonal antibodies were well-tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups18. Other ongoing trials include Storm Chaser and Tackle COVID-19; although they are focused on the post-exposure prevention of severe COVID-19 in subjects already exposed to the viral agent, they confirm the safety and tolerability profile of Evusheld in accordance with what emerged from the Provent trial. In Italy, following the publication of AIFA determination N. 42 of 19.02.2022, starting from 20.02.2022 it is possible to use the combination of Evusheld monoclonal antibodies (Tixagevimab-Cilgavimab) in specific and defined categories of patients who have severe immune system impairment including solid organ transplant recipients. In light of the encouraging data currently available, Evusheld could

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
88

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Pavia
      • Pavia, Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo di Pavia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

immunocompromised subjects with no serological response after third dose of mRNA vaccine

Description

Inclusion Criteria:

  • Adults >= 18 years-old and over, all sexes,
  • Negative SARS-COV2 serology tests befire enrollment,
  • Severe impairmentof the immune system induced by documented pathology, weight >= 40 kg at initial screening,
  • Written informed consent and any required authorization obtained from the partecipant prior to performing any protocol related procedures.

Exclusion Criteria:

  • Any condition that might compromise safety or interfere with study results,
  • Pregnant or nursing female.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
non-responder immunocompromised patients vaccinated with three doses of mRNA vaccines
Drug: Evusheld
Treatment with Evusheld
non-responder immunocompromised patients recipients of solid organ transplantation
Other: Control
No treatment with Evusheld

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
percentage of patients with symptomatic SARS-CoV-2 infection
Time Frame: up to 2 years
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 8, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 11, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REALISE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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