Phase II/III Study of AZD2816, a Vaccine for the Prevention of COVID-19 in Adults

This Data Sharing Agreement authorises the use of information voluntarily provided to NHS Digital by individuals who have given permission to be contacted about potential participation in COVID-19 vaccine clinical trials. The data will be processed on behalf of the data controller, AstraZeneca UK Limited, by NHS Digital as a data processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by AstraZeneca UK Limited.

The following provides background to the Permission to Contact (PtC) Service:

NHS Digital has agreed to work in partnership with the National Institute of Health Research (NIHR) to build and host a first of type online Permission to Contact (PtC) Service on nhs.uk where members of the public can register their details and give their permission to be contacted by researchers working on NIHR approved UK coronavirus vaccine trials about participating in those trials. This PtC Service, which is called “Sign Up to be Contacted about Coronavirus Vaccine Studies” on the nhs.uk website was launched as a national service on 20th July 2020.

This Service enables participants to:

• Provide permission for NHS Digital to share an individual’s details provided through the Service with the researchers undertaking COVID-19 UK vaccine trials for the purposes of researchers contacting that individual about taking part in those trials.

• Provide their permission to be contacted by NHS Digital about progress and outcomes from CV19 vaccine studies and in relation to the development of the PtC Service, including to inform them of opportunities to participate in other types of health research.

The data collected from individuals who sign up includes sufficient information to achieve the following purposes:

• Matching potentially eligible participants to eligibility criteria provided by the vaccine trials for their specific studies. This data will comprise of age, sex, geographic locations, type of employment, and a number health question e.g. about whether they have long-term health conditions.

• Providing relevant details of potentially eligible participants which have been obtained through the Service to researchers. This will allow the researchers to contact the participants with a view to discussing their taking part in a trial and if so, to obtain their further permission to take part in the trial.

• NHS Digital will provide access to the information obtained from individuals through the Service via the existing Data Access Request Service (DARS) process available to researchers working on UK COVID-19 vaccine trials sponsored by the National Institute of Health Research. The Service will only provide researchers with the data collected directly from individuals themselves through the Service.

The contact details will be used to invite potentially eligible individuals to undertake an eligibility assessment and, if eligible, to give informed consent to participate in this trial. NHS Digital, as data processor acting on behalf of AstraZeneca UK Limited, will be sending the email to eligible participants.

This request relates specifically to a vaccine trial.

Recently, several variants of the SARS-CoV-2 virus with increased transmissibility have emerged, including B.1.1.7, first identified in the UK, P.1, first identified in Brazil, and B.1.351, first identified in South Africa. In an ongoing clinical trial of AZD1222 in South Africa, interim results failed to show protection against mild to moderate disease caused by the B.1.351 variant; protection against severe disease could not be determined as no severe cases were identified.

Based on available evidence about vaccine effectiveness and molecular epidemiology of emerging variants, B.1.351 is estimated to have a potential to escape vaccine-induced immunity. B.1.351 carries sequence mutations in common with other variants of concerns; immunity to B.1.351 therefore has the potential to provide some cross-immunity against other emerging strains. Development of candidate vaccines that include the B.1.351 S-protein variant is underway. AstraZeneca is developing AZD2816, a vaccine against the B.1.351 SARS-CoV-2 variant using the same ChAdOx1 platform and manufacturing processes used for AstraZeneca’s currently available COVD-19 vaccine, AZD1222.

The trial is aiming to recruit 900 volunteers. The initial mailout will aim for around four / five times the number of potential participants to be recruited and therefore the estimate is for around 4,500 individuals to be contacted.

The data will be used in support of the development of a commercial vaccine that, should the research prove successful, will generate income for AstraZeneca UK Limited to cover both the development costs of the vaccine and also generate profit for that organisation.

NHS Digital will extract a list of patients meeting the following criteria, where that criteria can be ascertained using the PtC registry:

INCLUSION CRITERIA:

● Adult, ≥ 30 years of age at the time of consent

● No history of laboratory-confirmed SARS-CoV-2 infection (ie, no positive nucleic acid amplification test and no positive antibody test).

● Seronegative for SARS-CoV-2 at screening (lateral flow test to detect reactivity to the nucleoprotein).

● Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up:

- A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months prior to enrollment

● Able to understand and comply with study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative) based on the assessment of the investigator

● Signed informed consent obtained before conducting any study-related procedures

● Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

● Female participants:

● Women of childbearing potential must:

- Have a negative pregnancy test on the day of screening and on days of vaccination

- Use one highly effective form of birth control for at least 28 days prior to Day 1 and agree to continue using one highly effective form of birth control through 30 days following administration of the last dose of study intervention. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.

- Periodic abstinence, the rhythm method, and withdrawal are NOT acceptable methods of contraception.

● Prior completion of a 2-dose primary homologous vaccination regimen against SARS-CoV-2 with either AZD1222 (2 standard doses as authorized vaccine or as investigational product in a clinical trial with a 4- to 12-week dosing interval) or with an mRNA vaccine approved for emergency or conditional use (eg, BNT162b2 vaccine [Pfizer-BioNTech]

● with a 3- to 12-week dosing interval or mRNA-1273 vaccine [Moderna] with a 4- to 12- week dosing interval). The second dose in all cases should have been administered at least 3 months prior to first administration of study intervention.

EXCLUSION CRITERIA:

History of allergy to any component of AZD1222/AZD2816.

History of Guillain-Barré syndrome, any demyelinating disease, or any other neuroimmunologic condition

● Significant infection or other acute illness, including fever > 100 °F (> 37.8 °C) on the day prior to or day of randomization

● Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia or HIV/AIDS.

● Recurrent severe infections and use of immunosuppressant medication within the past 6 months (≥ 20 mg per day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to administration of study intervention)

● The following exceptions are permitted:

- Topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days)

● History of primary malignancy except for:

(a) Malignancy with low potential risk for recurrence after curative treatment (for example, history of childhood leukaemia) or for metastasis (for example, indolent prostate cancer) in the opinion of the site investigator.

(b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

(c) Adequately treated uterine cervical carcinoma in situ without evidence of disease

(d) Localized prostate cancer, History of thrombocytopenia and/or thrombosis, including participants who have experienced major venous and/or arterial thrombosis in combination with thrombocytopenia following vaccination with any COVID-19 vaccine

● History of heparin-induced thrombocytopenia, congenital thrombophilia (ie, factor V Leiden, prothrombin G20210A, antithrombin III deficiency, protein C deficiency and protein S deficiency, factor XIII mutation, familial dysfibrinogenemia), auto-immune thrombophilia (antiphospholipid syndrome, anti-cardiolipin antibodies, anti-β2- glycoprotein 1 antibodies), or paroxysmal nocturnal haemoglobinuria.

● Clinically significant bleeding (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venepuncture

● Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator (note, mild/moderate well-controlled comorbidities are allowed)

● Any other significant disease, disorder, or finding that 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.

● Any autoimmune conditions, except mild psoriasis and vitiligo

● Receipt of or planned receipt of investigational products indicated for the treatment or prevention of SARS-CoV-2 or COVID-19 with the exception of prior vaccination with AZD1222 or an mRNA COVID-10 vaccine (2 doses of the same vaccine within an approved dosing interval, see Section 5.1.2), which is allowed for participants in the previously vaccinated cohort

● Note: For participants who develop COVID-19, receipt of licensed treatment options and/or participation in investigational treatment studies is permitted

● Receipt of any vaccine (licensed or investigational) other than licensed influenza vaccines within 30 days prior to or after administration of study intervention

● Receipt of any influenza vaccine (licensed or investigational) within 7 days prior to and after administration of AZD1222/AZD2816.

● Receipt of immunoglobulins and/or any blood products within 3 months prior to administration of study intervention or expected receipt during the period of study follow-up

● Involvement in the planning and/or conduct of this study (applies to both Sponsor staff and/or staff at the study site)

● Women who are currently pregnant (confirmed with positive pregnancy test), breastfeeding, having given birth less than 3 months before or planning pregnancy during the study.

● Has donated ≥ 450 mL of blood products within 30 days prior to randomization or expects to donate blood within 90 days of administration of second dose of study intervention

● Participants with a history of chronic alcohol or drug abuse or any condition associated with poor compliance.

● Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements or if vaccination would interfere with the participant’s ongoing treatment.

● Previous enrollment in the present study.

The inclusion and exclusion criteria noted above is based on the information provided by cohort members on the permission to contact dataset (where it can be obtained from this dataset), and is not collected from other NHS data sources. Some of the above inclusion and exclusion criteria will be used by the sites during the Screening phase.

NHS Digital will identify all individuals within the PtC dataset meeting the relevant criteria and will extract their names, email addresses and postcodes.

It is not known in advance how many individuals meeting the above criteria will have records in the PtC dataset. The number may be amended and the process may be repeated depending on the level of response. In the event of the trial not achieving a suitable balance in recruited participants, such as an uneven ratio of males to females, subsequent mail outs may restrict the required criteria to a greater degree than previously, for example, only requesting details for male participants as opposed to both males and females. This could encompass any part of the criteria, such as age, gender, ethnicity or location and various others, depending on how the recruitment progresses.

NHS Digital will write to the individuals in the subset inviting them to participate within the trial using ethically approved text provided by AstraZeneca UK Limited. The email will remind the individuals of the background of the permission to contact programme and give them the opportunity to state that they do not wish to be contacted again. The email will also direct volunteers to NIHR’s Be Part of Research website to access study information and regional contact information.

Individuals will not be contacted multiple times under this Agreement and NHS Digital will record the fact that the individuals have been contacted to ensure compliance with the maximum number of contacts outlined as part of consent. Furthermore, in order to ensure that NHS Digital are able to update the register with which participants are registered with an active trial, and therefore prevent them from being invited to any further trials, NHS Digital will be provided with regular updates of those registered participants who have consented. This sharing of information is built into the Permission to Contact signing up information and will also be added to the trial consent and participant information.

IQVIA LTD will supply individual recruitment sites with the IDs of those patients who have gone through the pre-screener in order to invite them for further screening. Individual trial recruitment sites will supply NHS Digital with details of those who have signed up to take part in their trial so that NHS Digital can suitably capture this information within the Permission To Contact registry. All data that flows to NHS Digital in this context falls under the controllership of AstraZeneca UK Limited. Once it is received at NHS Digital then NHS Digital become controller for that data in their existing role as controller of the Permission To Contact Registry.

Due to the nature of trial recruitment sites, they often only become confirmed as sites very close to recruitment, and so NHS Digital will leave the responsibility with the lead site / data controller to appointment data processors themselves under their own due diligence. This practice aligns with their obligations under GDPR as a data controller and the emphasis will be on the lead site / data controller to appoint appropriate data processors on their behalf. Ordinarily NHS Digital would carry out these checks, but attempting to do so for this service would cause unnecessary delay to the initial application, as well as potentially multiple and costly amendments thereafter. Therefore all recruitment sites / data processors and their processing activities will be covered under a suitable processing agreement between themselves and the lead site / data controller which does not require NHS Digital’s inclusion. Specific details of recruitment sites, such as key contact, location, will therefore not be made known to NHS Digital unless there is a specific reason to do so.

Additionally, AstraZeneca UK Limited have an appropriate data processing agreement in place with IQVIA LTD to support the recruitment into the trial under AstraZeneca UK Limited’s controllership

No other processing of the data will take place and the data will not be linked with information from any other sources.

AstraZeneca UK Limited will not have access to any of the data being disseminated by NHS Digital under this agreement.

The information from NHS Digital will be used to facilitate contact with individuals who are potentially eligible and who have indicated willingness to potentially participate in studies/trials of COVID-19 vaccines.

This is expected to result in individuals entering the trials screening process with a view to them participating in the trial with fully informed consent.

The main results from this trial are expected to inform development of a safe and effective multiple vaccine combination against COVID 19.

The primary benefit of using the data will be to recruit participants for the clinical study/trial in a manner which:

• Enables individuals to volunteer in advance to participate in COVID-19 vaccine trials as an alternative to other potentially more intrusive mechanisms, e.g. sharing data with researchers about individuals under section 251 consents or COPI notices, which although lawful is initially less transparent.

• Allows researchers to identify a suitable cohort and recruit them quickly into the vaccine trials – thus reducing the overall time to recruit into the trials and to accelerate the delivery of an effective vaccine to treat individuals to manage the COVID-19 outbreak and to save lives.

• Reduces burden on research staff in identifying and contacting potential clinical trial participants.

• Supports the Vaccines Taskforce objectives to drive forward, expedite and coordinate efforts to research and then produce a coronavirus vaccine and make sure one is made available to the public as quickly as possible.

Yielded Benefits is not a requirement for new applications.