A Phase 2/3, Randomized, Stratified, Observer-blind Study to Evaluate the Immunogenicity and Safety of mRNA-1273.529 (B.1.1.529, Omicron variant) in Comparison with mRNA-1273 (prototype) Booster Vaccine

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, ModernaTX, Inc, by NHS Digital as a data processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by ModernaTX, Inc.

ModernaTX, Inc (also known as Moderna, Inc and previously known as Moderna Therapeutics, Inc) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. ModernaTX, Inc solely determine the purposes and means of the processing in this study, and the way the study is conducted and is therefore considered the sole Data Controller for this agreement. Additionally, Informa UK Ltd, who are a publishing company serving tech businesses and professionals, are acting as a data processor on behalf of ModernaTX, Inc by managing the pre-screening website and passing details of potential participants on to the trial recruitment sites.

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 questions 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 ModernaTX, Inc will be sending the email to eligible participants.

This request relates specifically to a vaccine trial. The full title for this study is "A Phase 2/3, Randomized, Stratified, Observer-blind Study to Evaluate the Immunogenicity and Safety of mRNA-1273.529 (B.1.1.529, Omicron variant) in Comparison with mRNA-1273 (prototype) Booster Vaccine"

There is an urgent need for vaccination strategies that induce broader protection against SARSCoV2 variants of concern (VOC), including the Omicron variant, to decrease morbidity and mortality. In addition, it is currently not known whether breakthrough infections could occur long term due to waning antibody titers*. Based on the experience of mRNA1273, available under Emergency Use Authorisation (EUA), and leveraging the flexible nature of the messenger ribonucleic acid (mRNA) technology, ModernaTX, Inc are evaluating a mRNA vaccine to address the Omicron variant.

* An antibody titer is a type of blood test that determines the presence and level (titer) of antibodies in the blood. This test is carried out to investigate if there is an immune reaction triggered by foreign invaders (antigens) in the body.

In November 2021, the SARS-CoV-2 Omicron variant (B.1.1.529) was detected in South Africa and epidemiological information about its spread in other regions is being evaluated. Preliminary evidence suggests that the Omicron variant has transmission advantage over the Delta variant. The Omicron variant has significant antigenic change with a potential growth advantage. In addition, it contains potential antibody escape site mutations (such as the categorised mutations K417N, T478K, E484A, N501Y). Preliminary results from the Sponsor show that 1 month after completing the primary series, mRNA-1273-elicited serum neutralization of Omicron variant pseudovirus was not detectable. However, neutralization was observed at 2 weeks after an mRNA-1273 booster dose, although activity was reduced relative to the prototype D614G strain and remained lower than that observed against the prototype D614G strain at 1 month after the primary series. Further evaluation of the in vitro neutralization of the Omicron variant, using sera (an amber-coloured, protein-rich liquid which separates out when blood coagulates) from vaccines, is currently in progress.

Overall, this study will assess whether a single booster dose of the Moderna mRNA vaccine boosts antibody responses to the Omicron variant and the prototype strain. Participants who previously received 2 or 3 doses of a COVID-19 vaccine will receive a single booster dose of the Moderna mRNA-1273 or Moderna mRNA-1273.529 vaccines in this study

The aim is to recruit a total of approximately 3,000 participants. 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 xxxx individuals to be contacted.

The GDPR legal basis for processing the data is GDPR Article 6(1)(f): (the processing is necessary for your legitimate interests or the legitimate interests of a third party, unless there is a good reason to protect the individual’s personal data which overrides those legitimate interests) - The processing is necessary for legitimate interests and ModernaTX, Inc have completed a Legitimate Interests Assessment.

In addition to the above GDPR Legal Basis for Processing, this agreement refers to health data, which is a Special Category of Personal Data and therefore ModernaTX, Inc also relies upon Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject). NHS Digital is content that the purpose of this study is 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, thus clearly demonstrating that the study purpose is research into public health and therefore providing benefit to health and social care in the UK.

The data are required for research purposes in the public interest- meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data. The ways in which the processing of data will be of benefit to the public – thereby demonstrating that the processing is in the public interest – are described in section ‘5d. ii. Expected Measurable Benefits to Health and/or Social Care Including Target Date’.

- In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include:

i. The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS Digital’s acceptance criteria (see sections 2 and 5b of this application for further details) although it should be noted that ModernaTX, Inc is not receiving data from NHS Digital in this agreement;

ii. The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details);

iii. Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection;

iv. Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights.

In the interests of full transparency, it is noted here that the data will be used in support of the development of a commercial vaccine(s) that, should the research prove successful, will generate income for ModernaTX, Inc, to cover the development costs of the vaccine and also generate profit for the organisation.

NHS Digital will extract a list of patients meeting the following criteria, where that criteria can be ascertained using the NHS Digital COVID-19 Vaccine Research Registry:

Personal Information:

Age

Location

Sex at birth

Ethic Group

Health questions:

Flu Jab

Diabetes

Asthma

Lung conditions

Liver conditions

Heart conditions

Cancer treatment

Bleeding disorders

Immune system disorders

The inclusion and exclusion criteria noted above is based on the information provided by members on the NHS Digital COVID-19 Vaccine Research Registry (where it can be obtained from this dataset ), and is not collected from other NHS data sources.

NHS Digital will identify the required number of individuals within the NHS Digital COVID-19 Vaccine Research Registry 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 respond to the invitation. The process may be repeated, with amended numbers, depending on the level of response. This could encompass any part of the criteria, depending on how the recruitment progresses.

NHS Digital will contact individuals in the subset inviting them to participate within the trial using ethically approved text provided by ModernaTX, Inc. The communication 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 communication 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 registry 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.

Some of the above inclusion and exclusion criteria will be used by the recruitment sites during the Screening phase. During the screening phase, the study team will use further inclusion and exclusion criteria in order to further filter the potential participants to undertake consent and discuss the trial:

INCLUSION CRITERIA:

The rollout of licensed vaccines is impacting on the volunteers available to recruit to studies and the inclusion criteria, e.g., age range, as listed below will be adjusted in line with the current progress of vaccine deployment.

Each participant must meet all of the following criteria during the screening period and at Day 1, unless noted otherwise, to be enrolled in this study:

1. Male or female, at least 16 years of age at the time of consent (Screening Visit).

1. Investigator’s assessment that participant understands and is willing and physically able to comply with protocol-mandated follow-up, including all procedures.

2. Participant has provided written informed consent for participation in this study, including all evaluations and procedures as specified in this protocol.

3. Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as bilateral tubal ligation > 1 year prior to the Screening Visit, bilateral oophorectomy, hysterectomy, or postmenopausal (defined as amenorrhea for ≥ 12 consecutive months prior to the Screening Visit without an alternative medical cause). A folliclestimulating hormone (FSH) level may be measured at the discretion of the investigator to confirm postmenopausal status.

4. Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:

- Has a negative pregnancy test at the Screening Visit and on the day of vaccination prior to vaccine dose being administered on Day 1.

- Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1).

- Adequate female contraception is defined as consistent and correct use of a local health authority approved contraceptive method in accordance with the product label.

- Has agreed to continue adequate contraception through 90 days following vaccine administration.

5. Had received two prior doses of a COVID-19 vaccine that had first received authorisation/approval prior to December 2021.

6. Had received at least one COVID-19 mRNA vaccine as the most recent vaccine dose.

EXCLUSION CRITERIA:

Note that the following exclusion criteria is included based on documented safety grounds and has been ethically approved:

Participants meeting any of the following criteria, unless noted otherwise, will be excluded from the study:

1. Had significant exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 14 days, as defined by the CDC as a close contact of someone who has had COVID19.

2. Participant is acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled within the 28-day screening window and will retain their initially assigned participant number.

3. Had laboratory-confirmed diagnosis of COVID-19 in November 2021 or later.

4. Had received a COVID-19 vaccine within 3 months of Day 1.

5. Had received a total of 4 doses of COVID-19 vaccine.

6. Had received a COVID-19 vaccine at a dose different from the authorized/approved dose.

7. History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Clinically unstable is defined as a diagnosis or condition requiring significant changes in management or medication within the 2 months prior to screening and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition.

8. Reported history of congenital or acquired immunodeficiency, immunosuppressive condition, or immune-mediated disease requiring immunosuppressive treatment or other immunosuppressive condition.

9. Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos, psoriasis patches affecting skin over the deltoid areas).

10. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any components of mRNA vaccine.

11. Reported history of bleeding disorder that is considered a contraindication to intramuscular (IM) injection or phlebotomy.

12. Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. Asymptomatic conditions and conditions with no evidence of end organ involvement (eg, mild hypertension, dyslipidemia) are not exclusionary, provided that they are being appropriately managed and are clinically stable (ie, unlikely to result in symptomatic illness within the time course of this study). Illnesses or conditions may be exclusionary, even if otherwise stable, due to therapies used to treat them (eg, immune modifying treatments), at the discretion of the Investigator.

13. Had received systemic immunosuppressants or immune-modifying drugs for > 14 days in total within 181 days prior to screening (for corticosteroids ≥ 10 mg/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study.

14. Had received or plans to receive any licensed vaccine ≤ 28 days prior to the study injection (Day 1) or plans to receive a licensed vaccine within 28 days after the study injection (with the exception that approved seasonal influenza vaccine may be received by at least 7 and preferably 14 days apart from the study injection)

15. Had received systemic immunoglobulins or blood products within 90 days prior to the Screening Visit or plans to receive during the study.

16. Diagnosis of malignancy within previous 10 years (excluding nonmelanoma skin cancer).

17. Had donated ≥ 450 mL of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study.

18. Had participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study.

19. Is an immediate family member or household member of study personnel, study site staff, or Sponsor personnel.

ModernaTX, Inc are partnering with Informa UK Ltd to support recruitment for the mRNA-1273-P305 clinical trial, specifically using their Citeline Connect platform. This platform will be used to host a trial landing page and pre-screener that will send pre-qualified referrals to participating research sites. Interested volunteers will be directed to the trial landing page, where they can learn about the trial and then complete a brief pre-screener to determine if they may be eligible. Qualified volunteers then have the option of submitting their contact information to a nearby site, using postal code matching, and sites will receive these prequalified referrals in the Citeline Connect portal.

ModernaTX, Inc have an appropriate data processing agreement in place with Informa UK Ltd to support the recruitment into the trial under ModernaTX, Inc controllership.

Informa UK 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 NHS Digital COVID-19 Vaccine Research Registry. All data that flows to NHS Digital in this context falls under the controllership of ModernaTX, Inc. Once it is received at NHS Digital then NHS Digital become controller for that data in their existing role as controller of the NHS Digital COVID-19 Vaccine Research Registry.

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

ModernaTX, Inc and Informa UK Ltd 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 allow researchers to identify a suitable cohort and recruit them quickly into the vaccine trial – thus reducing the overall time to recruit into the trials. This is expected to accelerate the delivery of an effective vaccine to treat individuals to manage the COVID-19 outbreak and to save lives.

It is expected that this will reduce the burden on research staff in identifying and contacting potential clinical trial participants. It is anticipated this will also support 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.