CLEAR: A Multi-Centre, Single-arm, Observational Study of EVUSHELD in China
Study Details
Study Description
Brief Summary
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.
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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 Design
Outcome Measures
Primary Outcome Measures
- To describe the baseline demographic and clinical characteristics of individuals receiving AZD7442 for pre-exposure prophylaxis [when receive AZD7442]
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, , 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
Secondary Outcome Measures
- To describe the baseline demographic and clinical characteristics of individuals receiving AZD7442 for pre-exposure prophylaxis by population subgroup of key basic disease. [when receive AZD7442]
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
- 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 12 months after first administration of AZD7442 for pre-exposure prophylaxis [12 months after first administration of AZD7442 for pre-exposure prophylaxis]
Medically attended COVID-19 rate SARS-CoV-2 infection rates (asymptomatic or symptomatic) Type of COVID-19 Variant COVID-19 mortality rates COVID-19 hospitalisation rates COVID-19 intensive care unit (ICU) Admission rates
- To describe the incidence of all-cause hospitalization and mortality during the 12 months after first administration of AZD7442 for pre-exposure prophylaxis [during the 12 months after first administration of AZD7442 for pre-exposure prophylaxis]
All cause hospitalisation rate All-cause mortality rate
- To describe COVID-19 risk behaviours at the time of AZD7442 injection and during the 12 months after first administration of AZD7442 for pre-exposure prophylaxis [during the 12 months after first administration of AZD7442 for pre-exposure prophylaxis]
• AstraZeneca-developed Risk Behaviour Questionnaire (Appendix A)
- To describe COVID-19-related healthcare resource utilisation (HCRU) during the 12 months after first administration of AZD7442 for pre-exposure prophylaxis [during the 12 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
- To describe the safety of AZD7442 during the 12 months after first administration of AZD7442 [during the 12 months after first administration of AZD7442 for pre-exposure prophylaxis]
Serious adverse events (SAEs) Adverse events of special interest (AESIs) Adverse drug reaction (ADR)
Other Outcome Measures
- 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. [12 months following AZD7442 first administration for pre-exposure prophylaxis]
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
- To describe the incidence of long COVID syndrome following AZD7442 first administration for pre-exposure prophylaxis [12 weeks from first onset of COVID-19 symptoms]
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)
- To describe the baseline and repeat administration(s) of AZD7442 [when receive 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
- To describe the usage purpose of AZD7442 [when receive 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
Eligibility Criteria
Criteria
Inclusion Criteria
Subjects who fulfil all the following inclusion criteria will be eligible to participate in the study:
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Individuals receiving AZD7442 before enrolment date or have been prescribed or have planned to administrate at enrolment date.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
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| 1 | (2) Ruijin-Hainan Hospital Shanghai Jiaotong University School of Medicine (Hainan Boao Research Hospital) | Qionghai | Hainan | China |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Jieming Qu, Doctor, 18917762988
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D8850R00019