Novavax developed a vaccine (Nuvaxovid(TM) vaccine) which was approved for use in the United Kingdom in February 2022 for immunisation to prevent COVID-19 caused by the SARS-CoV-2 virus in individuals 12 years of age and older.
The aim of the proposed study is to characterise the safety profile of Nuvaxovid(TM) vaccine in a real-world setting in England. The objective is to evaluate the risk of select safety outcomes of interest following vaccination with Nuvaxovid(TM) vaccine. Examples of safety outcomes include myocarditis, stroke, heart attack and anaphylaxis.
All individuals registered at English practices in the Clinical Practice Research Datalink (CPRD) Aurum database who receive a dose of Nuvaxovid(TM) vaccine will be considered for inclusion in the study. CPRD Aurum primary care and linked secondary care and mortality data will be used to define the safety outcomes and patient characteristics.
The study will assess the risk of select safety outcomes of interest after vaccination with Nuvaxovid(TM) vaccine, by comparing a period of time immediately after a person receives the vaccine with a later period of time in the same patient.
The results of this study will be shared with global regulatory authorities, including the Medicines and Healthcare products Regulatory Agency (MHRA), the European Medicines Agency (EMA), and the Food and Drug Administration (FDA). The findings of this work, along with other studies, are important to characterize the safety profile of Nuvaxovid(TM) vaccine when used in a real-world setting.
Novavax developed a COVID-19 vaccine (Nuvaxovid(TM) vaccine) which has been approved for use by the Medicines and Healthcare products Regulatory Agency (MHRA) to prevent COVID-19 caused by the SARS-CoV-2 virus in individuals 12 years of age and older.
Individuals in the Clinical Practice Research Datalink (CPRD) Aurum database who are registered with a general practitioner (GP) in England, are eligible for data linkage, and have received any dose of Nuvaxovid(TM) vaccine will be eligible for inclusion in the analysis for the objective. CPRD Aurum and linked data from Hospital Episode Statistics (HES) databases, Office for National Statistics Death Registration, Second Generation Surveillance System (SGSS), COVID-19 Hospitalisation in England Surveillance System (CHESS), and the Intensive Care National Audit & Research Centre (ICNARC) will be used to assess the risk of select safety outcomes of interest in patients after vaccination with Nuvaxovid(TM) vaccine. Examples of safety outcomes include myocarditis, stroke, heart attack, and anaphylaxis.
A self-controlled case series (SCCS) will make within-person comparisons of the incidence of select safety outcomes of interest in pre-specified risk windows following any dose of Nuvaxovid(TM) vaccine with incidence in a post-vaccination control window. Secondary objectives will compare incidence after: receipt of a first dose; completion of a two-dose primary series; receipt of a booster dose; and among subgroups of interest after any dose. Conditional Poisson regression models will be used to calculate Incidence Rate Ratios (IRR) for each safety outcome.
Exploratory objectives will use a retrospective matched cohort design to compare the incidence of select safety outcomes in individuals exposed to Nuvaxovid(TM) vaccine with: 1) matched individuals exposed to the Pfizer-BioNTech COVID-19 vaccine; 2) matched individuals exposed to the Moderna COVID-19 vaccine; and 3) matched unvaccinated individuals.
The results of this study will be provided to global regulatory authorities.
Occurrence of and risk for Adverse Events of Special Interest (AESI) for COVID-19:
Guillain-Barre syndrome; Transverse myelitis; Encephalomyelitis/encephalitis; Seizures; Non-haemorrhagic stroke; Haemorrhagic stroke; Narcolepsy/cataplexy; Bell’s palsy; Acute myocardial infarction; Myocarditis/pericarditis; Arterial dissection; Cardiac failure; Cardiomyopathy; Cardiac arrest; Deep vein thrombosis (VTE); Pulmonary embolism (PE); Cerebral venous sinus thrombosis (CVST); Disseminated intravascular coagulation; Thrombosis with thrombocytopenia syndrome (TTS), unusual and common site; Capillary leak syndrome; Immune thrombocytopenia; Anaphylaxis; Multisystem inflammatory syndrome in adults (MIS-A); Multisystem inflammatory syndrome in children (MIS-C); Autoimmune/inflammatory eye disorders, including uveitis; Autoimmune hepatitis; Appendicitis; Kawasaki disease; Acute cholecystitis; Ocular motor nerve disorders.
The following outcomes will be explored as part of exploratory analyses only:
Vaccine-associated enhanced disease (VAED); all-cause mortality.
Sonia Coton - Chief Investigator - CPRD
Zara Cuccu - Corresponding Applicant - CPRD
Eleanor Axson - Collaborator - CPRD
Helen Booth - Collaborator - CPRD
Jessie Oyinlola - Collaborator - CPRD
Jonathan Fix - Collaborator - Novavax, Inc.
Rachael Williams - Collaborator - CPRD
T Christopher Mast - Collaborator - Novavax, Inc.
Tarita Murray-Thomas - Collaborator - CPRD
Zara Cuccu - Collaborator - CPRD
Nicole Baker - Collaborator - Novavax, Inc.
CHESS (Hospitalisation in England Surveillance System);HES Admitted Patient Care;HES Outpatient;ICNARC (COVID-19 Intensive Care National Audit and Research Centre);ONS Death Registration Data;Patient Level Index of Multiple Deprivation;SGSS (Second Generation Surveillance System);COVID-19 Linkages;Rural-Urban Classification