PROVENT - A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study in Adults to Determine the Safety and Efficacy of AZD7442, a Combination Product of Two Monoclonal Antibodies (AZD8895 and AZD1061), for Pre-exposure Prophylaxis of COVID-19

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, IQVIA LTD, by the data processor, NHS Digital, 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 this study, will be sending the email to eligible participants.

This is a Phase III, randomized, double-blind, placebo-controlled, multi-country, multi-center study assessing the safety and efficacy of a single dose of AZD7442 (× 2 IM injections) compared to placebo for the prevention of COVID-19.

Participants will be adults ≥ 18 years of age who are candidates for benefit from passive immunisation with antibodies, defined as having increased risk for inadequate response to active immunization (predicted poor responders to vaccines or intolerant of vaccine), or having increased risk for SARS-CoV-2 infection, defined as those whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-19, based on available risk assessment at the time of enrolment.

Numbers required for the trial:

- 300 participants recruited between 02/11/2020 and 05/11/2020.

- 700 participants (7 - 9 days later)

Total breakdown:

1) 250 over 60 years - care homes/sheltered

2) 250 under 60 years

3) 250 Healthcare workers

4) 250 Participants with comorbidities

The initial mailout will aim for 5,000 potential participants to be contacted. The aim is to recruit the first patient into the trial on 02/11/2020.

The data will be used in support of the development of a commercial compound that, should the research prove successful, will generate income for AstraZeneca UK Limited to cover both the development costs of the compound 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:

18+

Increased risk for inadequate response to active immunisation (predicted poor responders to vaccines) defined as:

- Elderly, ie, ≥ 60 years old

- Obese, ie, BMI ≥ 30

- Congestive heart failure

- Chronic obstructive pulmonary disease

- Chronic kidney disease, ie, GFR < 30 mL/min/1.73 m2

- Chronic liver disease

- HIV infection

- Persons with solid organ transplants

- Immunosuppressive therapy

- Intolerant of vaccine

Increased risk for SARS-CoV-2 infection, defined as those whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-19, based on available risk assessment at the time of enrollment, including:

- Health care workers, including staff of long-term care facilities (including skilled nursing facilities, assisted living facilities, and independent living facilities for senior adults)

- Workers in industrial settings shown to have been at high risk for SARS-COV-2 transmission, including but not limited to meatpacking plants

- Military personnel residing or working in high-density settings including but not limited to barracks, ships, or close-quarters working environments

- Students living in dormitory settings

- Others living in settings of similar close or high-density proximity

EXCLUSION CRITERIA:

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

- History of laboratory-confirmed SARS-CoV-2 infection

- History of infection with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS).

- Known history of allergy or reaction to any component of the study drug formulation.

- Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.

- Any prior receipt of investigational or licensed vaccine or other mAb/biologic indicated for the prevention of SARS-CoV-2 or COVID-19 or expected receipt during the period of study follow-up.

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

- Currently pregnant (confirmed with positive pregnancy test) or breast feeding.

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. Additional exclusion criteria will be used by the site during the Screening phase.

NHS Digital will identify all individuals within the PtC dataset meeting the above 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 AstraZeneca UK Limited to appointment sites as 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 AstraZeneca UK Limited 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 AstraZeneca UK Limited, which does not require NHS Digital’s inclusion. Specific details of recruitments 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, with fully informed consent, in the Investigating a Vaccine Against COVID-19 study.

The main trial results of Investigating a Vaccine Against COVID-19 study are expected to inform development of a safe and effective vaccine 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.