Study on Determine the Utilisation and Clinical Outcomes of Evusheld in COVID-19 PrEP in China (CLEAR)

Study on Clinical Use of Evusheld (AZD7442) in the Real-world Setting - A Multi-Centre, Single-arm, Observational Study to Determine the Utilisation and Clinical Outcomes of Evusheld in China

Evusheld(AZD7442) is a combination of 2 human long-acting antibodies, which was selected for maximal potency and demonstrated synergistic neutralization of SARS-CoV-2 in vitro. PROVENT is a Phase III study in participants at an increased risk for inadequate response to COVID-19 vaccine, an increased risk of exposure to SARS-CoV-2 or both. The study met the primary endpoint of reduction in the incidence of symptomatic Coronavirus disease 2019 (COVID-19) with tixagevimab/cilgavimab (TIXA/CILGA) compared with placebo, risk reduction 76.7% (95% CI, 46.0-90.0), in 5172 patients who did not have a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Reverse transcription polymerase chain reaction (RT-PCR) positive COVID-19 infection at baseline. Although the PROVENT trial was invaluable in demonstrating AZD7442's ability to prevent symptomatic infection, it was conducted in highly controlled environments using a rigorous protocol, which does not accurately reflect the patient experience in clinical practice. Furthermore, the sample size of Asian population in phase 3 clinical trials is small (110 subjects in AZD7442 group and 60 subjects in placebo group), and there is very limited clinical trial/real-world data in Chinese population is reported. Therefore, this current study aims to describe the utilisation and clinical outcomes of AZD7442 in Chinese population for pre-exposure prophylaxis.

Study Overview

• Status: Completed
• Conditions: COVID-19

Detailed Description

COVID-19 has a spectrum of clinical manifestations and multisystem organ involvement due to SARS-CoV-2, viral dynamics may correlate to the severity of illness and disease outcomes. Despite the increase in COVID-19 vaccine roll-out, many individuals still remain at high risk of breakthrough infection and many of these individuals are also at higher risk of poor COVID-19 outcomes. In the US about 3% of the adult population is moderately to severely immunocompromised, leading to increased vulnerability to COVID-19.

AZD7442 is a combination of 2 human long acting antibodies, which was selected for maximal potency and demonstrated synergistic neutralization of SARS-CoV-2 in vitro. AZD7442 are 2 monoclonal antibodies that independently neutralize SARS-CoV-2 with high potency in vitro. AZD7442 targets SARS-CoV-2 spike protein to prevent virus entry into host cells.

PROVENT is a Phase III study in participants at an increased risk for inadequate response to COVID-19 vaccine, an increased risk of exposure to SARS-CoV-2 or both. The study met the primary endpoint of reduction in the incidence of symptomatic COVID-19 with TIXA/CILGA compared with placebo, risk reduction 76.7% (95% CI, 46.0-90.0), and longer (median 6-month) follow-up showed a risk reduction of 82.8%, in 5172 patients who did not have a SARS-CoV-2 RT-PCR-positive COVID-19 infection at baseline. Most adverse events were mild or moderate in intensity, with the overall adverse event profile over a median follow-up of 6 months remaining similar to the primary safety analysis. At either the primary or 6-month analyses, there were no cases of severe/critical COVID-19 in those treated with AZD7442. In the placebo arm, there were 5 cases of severe/critical COVID-19 in total.

Although the PROVENT trial was invaluable in demonstrating AZD7442's ability to prevent symptomatic infection, it was conducted in highly controlled environments using a rigorous protocol, which does not accurately reflect the patient experience in clinical practice. Furthermore, the sample size of Asian population in phase 3 clinical trials is small (110 subjects in AZD7442 group and 60 subjects in placebo group), and there is very limited clinical trial/real-world data in Chinese population is reported.

Studies are therefore needed to understand who is being administered AZD7442 in the real world, the frequency of COVID-19 related events, and healthcare resource utilisation (HCRU). Also, important to understand is the potential impact that AZD7442 administration may have on COVID-19 risk behaviours (particularly shielding and other preventive measures), which may in turn influence interpretation of AZD7442 effectiveness results. Such information is imperative to inform clinical decision-making for the care of this relatively vulnerable population.

Therefore, this current study aims to describe the utilisation and clinical outcomes of AZD7442 in Chinese population for pre-exposure prophylaxis. Although this study will not evaluate the effectiveness of AZD7442, the descriptive results may guide further development of studies to assess real world effectiveness of AZD7442. The study is planned to be conducted in approximately 100 sites in China.

• Study Type: Observational
• Enrollment (Actual): 248

Contacts and Locations

Study Locations

• China
  • Hainan
    • Qionghai, Hainan, China
      • (2) Ruijin-Hainan Hospital Shanghai Jiaotong University School of Medicine (Hainan Boao Research Hospital)

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Participants included in this this study are all individuals who have received AZD7442 since AZD7442 will be on market in China.

Description

Inclusion Criteria

Subjects who fulfil all the following inclusion criteria will be eligible to participate in the study:

• Individuals receiving AZD7442 before enrolment date or have been prescribed or have planned to administrate at enrolment date.
• Individuals willing and able to sign informed consent signed.

Exclusion Criteria

Subjects who fulfil any of the following exclusion criteria will not be eligible to participate in the study:

• Individuals currently participating in interventional clinical trials of SARS-CoV-2 prophylactic or treatments.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the baseline demographic and clinical characteristics of individuals receiving AZD7442 for pre-exposure prophylaxis	Proportion of individuals by demographic variables of interest (e.g. age, gender, race/ethnicity, smoking status, weight(kg) and height(cm) will be combined to reported body mass index(BMI) in kg/m^2, cities of frequency travel and residence, long-term care or assisted living, household composition, high risk contacts); Proportion of individuals by clinical characteristics of interest (e.g. comorbidities, prior and concurrent medications, including immunosuppressors by type/class); Proportion of individuals by baseline COVID-19 vaccination status or any history of exposure to other prophylactic interventions for prevention of SARS-CoV-2 exposure.; Proportion of individuals by baseline history of SARS-CoV-2 infection/COVID-19 diagnosis and disease severity.; Proportion of individuals by priority AZD7442 subpopulations of interest	up to 12 months before first administration of AZD7442 for pre-exposure prophylaxis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the baseline demographic and clinical characteristics of individuals receiving AZD7442 for pre-exposure prophylaxis by population subgroup of key basic disease.	To describe the baseline demographic and clinical characteristics of individuals receiving AZD7442 for pre-exposure prophylaxis by population subgroup of immune compromised disease, including haematological malignancies, solid organ transplant, autoimmune disease, solid tumour, chronic kidney disease (CKD; including dialysis) and others	up to 12 months before first administration of AZD7442 for pre-exposure prophylaxis
To describe the incidence of SARS-CoV-2 infection (asymptomatic or symptomatic), medically-attended COVID-19, and COVID-19 related hospitalization and death up to 6 months after first administrationxposure prophylaxis of AZD7442 for pre-e	Medically attended COVID-19 rate; SARS-CoV-2 infection rates (asymptomatic or symptomatic); Proportion of SARS-CoV-2 infection (asymptomatic or symptomatic) in close contacts; Proportion of SARS-CoV-2 infection from different cities; Type of COVID-19 Variant; COVID-19 mortality rates; COVID-19 hospitalisation rates; COVID-19 intensive care unit (ICU) admission rates	6 months after first administration of AZD7442 for pre-exposure prophylaxis
To describe the incidence of all-cause hospitalization and mortality during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis	All cause hospitalisation rate; All-cause mortality rate	during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis
To describe COVID-19 risk behaviours at the time of AZD7442 injection and during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis	• AstraZeneca-developed Risk Behaviour Questionnaire (Appendix A)	during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis
To describe COVID-19-related healthcare resource utilisation (HCRU) during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis	Hospitalization, and days hospitalised; Supplemental oxygen, and days under supplemental oxygen; Re-admission, days in hospital; ICU admissions and days in ICU; Emergency department (ED) visits; Outpatient visits/calls (specialist); COVID-19 related medications or treatment; Others	during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis
To describe the safety of AZD7442 during the 6 months after first administration of AZD7442	Serious adverse events (SAEs); Adverse events of special interest (AESIs); Adverse drug reaction (ADR)	during the 6 months after first administration of AZD7442 for pre-exposure prophylaxis

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the incidence of long COVID syndrome following AZD7442 first administration for pre-exposure prophylaxis	Proportion of subjects with long-COVID syndrome at >12 weeks from first onset of COVID-19 symptoms; Duration of long COVID syndrome: medium (days, interquartile range (IQR), minimum, maximum; and mean standard deviation)	12 weeks from first onset of COVID-19 symptoms
To describe the baseline and repeat administration(s) of AZD7442	Number, frequency of subjects administered AZD7442 by: Route of administration (e.g. IM or IV); Dose number, location (e.g. thigh or gluteus), amount and timing/interval between doses o Type of medical condition	when receive AZD7442
To describe the usage purpose of AZD7442	Number, proportion of subjects administered AZD7442 by: Pre-exposure Prophylaxis; Post-exposure Prophylaxis; Treatment of mild/Asymptomatic disease; Treatment of normal disease; Treatment of severe disease	when receive AZD7442
To describe the demographic and clinical characteristics of SARS-CoV-2 infection, medically attended COVID-19, and COVID-19 related hospitalized cases occurring in comparison to non-cases.	Proportion of individuals by demographic variables of interest (e.g. age, gender, race/ethnicity, smoking status, body mass index [BMI, weight in kilograms, height in meters, then weight and height will be combined to reported BMI in kg/m^2], long-term care or assisted living, high risk contacts); Proportion of individuals by clinical characteristics of interest (e.g. comorbidities, prior and concurrent medications, including immunosuppressors by type/class); Proportion of individuals by baseline COVID-19 vaccination status or any history of exposure to other prophylactic interventions for prevention of SARS-CoV-2 exposure; Proportion of individuals by baseline history of SARS-CoV-2 infection/COVID-19 diagnosis and disease severity; Proportion of individuals by priority AZD7442 subpopulations of interest	6 months following AZD7442 first administration for pre-exposure prophylaxis
To describe SARS-CoV-2 RNA viral load levelsafter symptomatic SARS-CoV-2 infection within 29 days after first administration of AZD7442 for treatment	• SARS-CoV-2 RNA viral load levels and changes in nasal swabs during hospitalization up to 29 days	within 29 days after first administration of AZD7442 for treatment
To describe the neutralising responses against SARS-CoV-2 subvariants of AZD7442 in serum (if applicable)	• Post treatment GMTs and GMFRs from baseline value through 6 month after single IM dose in SARS-COV-2 neutralizing antibodies (pseudo neutralization assay)	6 months following AZD7442 first administration for pre-exposure prophylaxis
To describe severe COVID-19 related hospitalization and ICU after symptomatic SARS-CoV-2 infection within 29 days after first administration of AZD7442 for treatment	Severe COVID-19 hospitalisation rates and days; COVID-19 intensive care unit (ICU) admission rates	within 29 days after first administration of AZD7442 for treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Jieming Qu, Doctor, 18917762988

Publications and helpful links

Helpful Links

• redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: June 21, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• 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: D8850R00019

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 Individual participant data(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 European Federation of Pharmaceutical Industries Associations (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. 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: No
• Studies a U.S. FDA-regulated device product: No