Covid-19 Living Data

Trial ISRCTN15638344; EudraCT 2020-005765-13
Publication Li G, Lancet, 2022
Dates: 2021-02-15 to 2021-04-02
Funding: Mixed (The Department of Health and Social Care, through the National Institute for Health Research ; AstraZeneca)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / UK Follow-up duration (months): 8.5
	ChAdOx1 D0/28 (n = 59) Control vaccine (capsular group B meningococcal) D0/28 (n = 16) ChAdOx1 D0/84 (n = 61) Control vaccine (capsular group B meningococcal) D0/64 (n = 14)
Inclusion criteria	Healthy adolescent aged 12-17 years (upper age limit is 17 years and 8 months so that both prime and booster are expected to take place prior to their 18th birthday) Able and willing (in the Investigator’s opinion) to comply with all study requirements (participant’s parents/guardians must not rely on public transport or taxis) Willing to allow the investigators to discuss the participant’s medical history with their General Practitioner and access all medical records when relevant to study procedures Parent/guardian to provide informed consent for participants under the age of 16 it will be assumed that participants aged 16 and over are able to provide consent for themselves, however parental support will be sought and investigators will reserve the right to refuse enrollment if concerns arise
Exclusion criteria	History of laboratory confirmed COVID-19 (A positive result on a validated test for SARS-CoV-2 or seropositivity for SARS-CoV-2 before enrolment) Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed) Prior receipt of MenB vaccine Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrolment Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines) Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection asplenia recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting <14 days) Any autoimmune conditions History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 or MenB vaccines Previous diagnosis of Kawasaki disease Any history of angioedema Any history of anaphylaxis Pregnancy, lactation or willingness/intention to become pregnant during the study Any history of cancer Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture Any other serious chronic illness requiring hospital specialist supervision Congenital cardiovascular conditions Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data Child of a staff member of the Oxford Vaccine Group
Interventions
	Intervention 2 IM standard doses (5.5×10^10 vp) ChAdOx1, 28 days apart 2 IM standard doses (5.5×10^10 vp) ChAdOx1, 112 days apart
	Control 2 IM standard doses control vaccine (0.5 mL MenB), 28 days apart2 IM standard doses control vaccine (0.5 mL MenB), 112 days apart
Participants
	Randomized 150 participants
	Characteristics of participants Type of participants: Adolescents N=150 76 males Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adolescents aged 12-17 years with no history of COVID-19 at 4 centers in the UK
Primary outcome
	In the register 1) Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination; 2) Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination; 3) Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination; 4) Occurrence of SAEs and disease enhancement episodes over course of study; 5) Occurrence of serious adverse events (SAEs) throughout study duration
	In the report 1) occurrence of solicited local and systemic adverse events up to 7 days after each vaccination; 2) unsolicited local and systemic adverse events up to 28 days after each vaccination; 3) serious adverse events
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, When the trials are complete. All data will be made available for a minimum of 5 years from the end of the trial. Data accessibility: corresponding author: Xinxue Liu, xinxue.liu@paediatrics.ox.ac.uk Data can be shared through a secure online platform after signing a data access agreement.
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the study registry and protocol were used in data extraction and risk of bias assessment. The article reports results for participants aged 12-17 years in a study that also recruited participants aged 6-11 years. Due to a temporary withholding of second doses of ChAdOx1 in adults under 30 years while further safety data were considered, the second dose in the Long Interval group was given at 112 days rather than the planned 84 days. The primary outcomes reported in the article were included in the registry. Disease enhancement, a primary outcome in the registry, was not reported in the article. The trial (n = 150) achieved its target sample size for 12-17 year olds (n = 150). This trial wwas updated on November 10th 2022, after publication of the study report.