A RANDOMIZED, OBSERVER-BLIND, CONTROLLED, SUPERIORITY STUDY TO COMPARE THE IMMUNOGENICITY AGAINST COVID-19, OF VLA2001 VACCINE TO AZD1222 VACCINE, 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, Valneva Austria GmbH, by NHS Digital as a data processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by Valneva Austria GmbH.

Data secured from individuals as a result of being contacted by the study is not covered within this agreement. This data relates solely to Valneva and not NHS Digital.

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 Valneva Austria GmbH, will be sending the email to eligible participants.

This request relates specifically to a vaccine trial. This is a Randomized, Observer-blind, Controlled, Superiority Study to Compare the Immunogenicity of VLA2001 to AZD1222 in terms of GMT of SARS-CoV-2-specific neutralizing antibodies.

Participants will be adults aged ≥ 18 years of age who are either generally healthy or are with a stable medical condition.

Approximately 4,000 participants will be randomized overall in a 3:1 ratio to receive 2 intramuscular doses of either VLA2001 (n=3,000) or AZD1222 (n=1,000) at the recommended dose level, 28 days apart, on Days 1 and 29.

For immunogenicity analyses, samples from approximately 1,200 participants (600 per group) who have been tested sero-negative for SARS-CoV-2 at screening will be analyzed.

All visits will be conducted at the clinical site on an outpatient basis.

Immunogenicity (neutralizing and binding antibody titers) and safety will be assessed up to month 12 after the first vaccination.

Participants will be observed for immediate AEs and/or reactogenicity for at least 30 minutes after the administration of the vaccine. The first 10 participants who are older than 55 years will be treated as a ‘sentinel’ group and will be observed for at least 60 minutes after each vaccination.

Participants will be provided with an electronic Diary (e-Diary) and will be trained to record specifically solicited systemic and local symptoms daily as well as any additional AEs during follow-up period after each of both vaccinations up to the next visit to the site until Day 43 visit has been completed. The following information will be collected:

- Oral body temperature

- Solicited local (i.e. injection site) reactions

- Solicited systemic reactions

- Other AEs

- Any new medications or changes in medication administered after vaccination

The initial mailout will aim for around four / five times the number of potential participants to be recruited and therefore the estimate is for 20,000 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 Valneva Austria GmbH 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:

Participants must meet all inclusion criteria to be eligible for the study.

1. Participants must have read, understood, and signed the informed consent form (ICF).

2. Participants of either gender aged 18 years and older at screening.

3. 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 the expected day of randomization (visit 1).

4. Must be able to attend all visits of the study and comply with all study procedures, including daily completion of the e-diary for 7 days after each vaccination.

5. Women of childbearing potential (WOCBP) must be able and willing to use at least 1 highly effective method of contraception (i.e. include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy, hormonal oral [in combination with male condoms with spermicide], transdermal, implant, or injection, barrier [i.e. condom, diaphragm with spermicide]; intrauterine device; vasectomized partner [6 months minimum], clinically sterile partner; or abstinence) for a minimum of 3 months after the last dose of study vaccine. A female participant is considered to be a WOCBP after menarche and until she is in a postmenopausal state for 12 consecutive months (without an alternative medical cause) or otherwise permanently sterile. Note: Participants not of childbearing potential are not required to use any other forms of contraception during the study. Non-childbearing potential is defined as participant confirmed:

Surgical sterilization (e.g., bilateral oophorectomy, bilateral salpingectomy, bilateral occlusion by cautery, hysterectomy, or tubal ligation). Postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to screening).

6. WOCBPs must have a negative pregnancy test prior to each vaccination.

EXCLUSION CRITERIA:

Participants will not be eligible for the study if they meet any of the exclusion criteria, or will be discontinued from study vaccination if they develop any of the following exclusion criteria during the study.

1. Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration

2. History of allergy to any component of the vaccine.

3. Significant infection (e.g. positive SARS-CoV-2 RT-PCR) or other acute illness, including fever > 100 °F (> 37.8 °C) 48 hours before vaccination.

4. Participant has a known or suspected defect of the immune system, such as participants with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno-suppressive therapy within 4 weeks prior to the expected day of randomization (Visit 1). Immuno-suppressive therapy is defined as administration of chronic (longer than 14 days) prednisone or equivalent ≥ 0.05 mg/kg/day within 4 weeks prior to the expected day of randomization (visit 1), radiation therapy or immunosuppressive cytotoxic drugs/ monoclonal antibodies in the previous 3 years; topical and inhaled steroids are allowed. Participants with chronic HIV unless: HIV disease with documented viral load <50 copies/ml and CD4 count >200 cells/mm3 for at least 6 months before enrolment, and stable antiretroviral therapy for the last 6 months.

5. Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.

6. Participant has a history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there has been surgical excision or treatment more than 5 years ago that is considered to have achieved a cure, the participant may be enrolled. A history of hematologic malignancy is a permanent exclusion. Participants with a history of skin cancer must not be vaccinated at the previous tumour site.

7. History of drug dependency or current use of drug of abuse or alcohol abuse at screening.

8. Significant blood loss (> 450 mL) or has donated 1 or more units of blood or plasma within 6 weeks prior to the expected day of randomization (Visit 1).

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

10. Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.

11. Any other significant disease, disorder or finding which in the opinion of the investigator may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study.

Prior/concomitant therapy:

12. Receipt of immunoglobulin or another blood product within the 3 months before expected day of randomization (visit 1) in this study or those who expect to receive immunoglobulin or another blood product during this study.

13. Receipt of medications and or vaccinations intended to prevent COVID-19.

14. Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).

Others:

15. Any member of the study team or sponsor.

16. An immediate family member or household member of the study’s personnel.

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 Valneva Austria GmbH. 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.

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 the data controller, regardless of whether they themselves are specifically involved in the processing of that data as it flows to NHS Digital. For this agreement there may be flows from each individual site. Once the data 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 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, Valneva Austria GmbH have an appropriate data processing agreement in place with Pharm-Olam to support the recruitment into the trial under Valneva Austria GmbH’s controllership. Pharm-Olam will not have access to any of the data being disseminated by NHS Digital under this agreement.

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

Valneva Austria GmbH 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 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.

Not stated in the register.