A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older

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, Janssen-Cilag 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 Janssen-Cilag Limited.

Janssen-Cilag Limited have provided delegated authority for IQVIA LTD as a processor for key activities in supporting trial recruitment. Clause E (in SD2.2 in the documents store), allows the delegation of ‘preparing and signing documents in accordance with Data Protection requirements’. SD2.1, within the same document store, sets this out in accordance with all applicable laws of the relevant countries as applicable. This includes IQVIA Ltd within the United Kingdom. Therefore James Brook of IQVIA LTD has been designated as delegated representative of Janssen-Cilag Limited for the purposes of signing this agreement on Janssen-Cilag Limited’s behalf.

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 the Vaccine Study, will be sending the email to eligible participants.

This request relates specifically to a vaccine trial.

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3, pivotal efficacy and safety study in adults ≥18 years of age. The efficacy, safety, and immunogenicity of Ad26.COV2.S will be evaluated in participants living in, or going to, locations with high risk for acquisition of SARS-CoV-2 infection after administration of 2 doses of study vaccine.

The study will consist of a screening phase of up to 28 days, a 60-week double-blind study period (including the administration of 2 doses of study vaccine (1 dose on Day 1 and 1 dose on Day 57), after randomization), and a long-term follow-up period of 1 additional year. The duration of individual participation, including screening, will be maximum 2 years and 3 months. If a participant is unable to complete the study, but has not withdrawn consent, an early exit visit will be conducted. The end-of-study is considered as the completion of the last visit for the last participant in the study.

Participants will be randomized in parallel in a 1:1 ratio to receive intramuscular (IM) injections of Ad26.COV2.S or placebo.

The data will be used in support of the development of a commercial vaccine that, should the research prove successful, will generate income for Janssen-Cilag 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 (for example, inclusion criteria, point 3; exclusion criteria, point 8).

INCLUSION CRITERIA:

Each potential participant must satisfy all of the following criteria to be enrolled in the study:

1. Participants must provide consent indicating that he or she understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study.

2. Participant is willing and able to adhere to the prohibitions and restrictions specified in this protocol.

3. Stages 1a and 2a: Participant is ≥18 to <60 years of age on the day of signing the ICF. Stages 1b and 2b: Participant is ≥60 years of age on the day of signing the ICF

4. Stage 1: In the investigator’s clinical judgement, participant must be either in good or stable health, including a BMI <30 kg/m2 . Participants may have underlying illnesses (not associated with increased risk of progression to severe COVID-19a,13 as specified in Exclusion Criteria 14), as long as their symptoms and signs are stable and well-controlled. If participants are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding the 1st vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of relevant medical history and BMI at screening. As of Stage 2: In the investigator’s clinical judgement, participant may have a stable and well controlled comorbidity associated with an increased risk of progression to severe COVID-19 (eg, stable/well-controlled HIV)*. 13 If participants are on medication for comorbidity associated with an increased risk of progression to severe COVID-19, the medication dose must have been stable for at least 12 weeks preceding the 1st vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of relevant medical history and BMI at screening. *Well controlled HIV infection includes: a. Participant has HIV-infection for at least 6 months prior to screening. b. CD4 cell count ≥300 cells/µL. c. Viral load <50 vp/mL. d. Participant must be on a stable anti-retroviral treatment (ART) for 6 months (unless the change is due to tolerability, in which case the regimen can be for only the previous 3 aPer US CDC (Appendix 11). In this study, (former) smoking/vaping and mild hypertension (according to the Toxicity Grading Scale in Section 10.9) will not be considered as a comorbidity. months; changes in formulation are allowed) and the participant must be willing to continue their ART throughout the study as directed by their local physician. Note: Participants with ongoing and progressive co-morbidities associated with HIV will be excluded but co-morbidities associated with HIV that have been clinically stable for the past 6 months are not an exclusion criterion. Laboratory methods for confirming a diagnosis of HIV are: Any evidence (historic or current) from medical records, such as ELISA with confirmation with Western Blot or PCR, or of a detectable viral load (country specific regulatory approved tests). A laboratory result within 6 months of screening does not need to be repeated.

5. Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies. Before randomization, participants must be either (as defined in Appendix 5): a. Not of childbearing potential b. Of childbearing potential and practicing an acceptable effective method of contraception and agrees to remain on such a method of contraception from providing consent until 3 months after the last dose of study vaccine. Use of hormonal contraception should start at least 28 days before the 1st administration of study vaccine. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the 1 st vaccination. Acceptable effective methods for this study include: 1. hormonal contraception: i. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal) ii. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable) 2. intrauterine device; 3. intrauterine hormone-releasing system; 4. bilateral tubal occlusion/ligation procedure; 5. vasectomized partner (the vasectomized partner should be the sole partner for that participant);

6. Sexual abstinence*. *Sexual abstinence is considered an effective method only if defined as refraining from heterosexual intercourse from providing consent until 3 months after the last dose of study vaccine. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. 6. All participants of childbearing potential must: a. Have a negative highly sensitive urine pregnancy test at screening b. Have a negative highly sensitive urine pregnancy test on the day of and prior to each study vaccine administration.

7. Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after the last dose of the study vaccine.

8. Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.

9. Must be able to read, understand, and complete questionnaires in the eCOA (ie, the COVID-19 signs and symptoms surveillance question, the e-Diary, and the electronic patient-reported outcomes (ePROs)).

EXCLUSION CRITERIA:

Any potential participant who meets any of the following criteria will be excluded from participating in the study:

1. Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhoea or mild upper respiratory tract infection) or temperature ≥38.0ºC (100.4°F) within 24 hours prior to the planned 1st dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor.

2. Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine; refer to the IB).

3. Participant has abnormal function of the immune system resulting from: a. Clinical conditions (eg, autoimmune disease, potential immune mediated disease or known or suspected immunodeficiency, chronic kidney disease (with dialysis) expected to have an impact on the immune response of the study vaccine. Participants with clinical conditions stable under non-immunomodulator treatment (eg, autoimmune thyroiditis, autoimmune inflammatory rheumatic disease such as rheumatoid arthritis) may be enrolled at the discretion of the investigator. Non-immunomodulator treatment is allowed as well as steroids at a non-immunosuppressive dose or route of administration. b. Chronic (>10 days) or recurrent use of systemic corticosteroids within 6 months before administration of the 1st dose of study vaccine and during the study. A substantially immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of 20 mg of prednisone or equivalent. Note: Ocular, topical or inhaled steroids are allowed. c. Administration of antineoplastic and immunomodulating agents or radiotherapy within 6 months before administration of the 1st dose of study vaccine and during the study.

4. Participant received treatment with Ig in the 3 months or blood products in the 4 months before the planned administration of the 1st dose of study vaccine or has any plans to receive such treatment during the study.

5. Participant received or plans to receive a. Licensed live attenuated vaccines – within 28 days before or after planned administration of the 1st or subsequent study vaccinations. b. Other licensed (not live) vaccines – within 14 days before or after planned administration of the 1st or subsequent study vaccinations.

6. Participant previously received a coronavirus vaccine.

7. Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months before the planned administration of the 1st dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study. See also Section 6.8. Note: Participation in an observational clinical study is allowed at the investigator’s discretion; please notify the sponsor (or medical monitor) of this decision. Efforts will be made to ensure inclusion of participants who have not been previously enrolled in coronavirus studies and to prevent participants from subsequently enrolling in other coronavirus studies during their participation in this study. The use of any coronavirus vaccine (licensed or investigational) other than Ad26.COV2.S is disallowed at any time prior to vaccination (see also Exclusion Criterion 6) and during the study.

8. Participant is pregnant or planning to become pregnant within 3 months after the last dose of study vaccine.

9. Participant has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the wellbeing) or that could prevent, limit, or confound the protocol-specified assessments.

10. Participant has a contraindication to IM injections and blood draws, eg, bleeding disorders.

11. Participant has had major psychiatric illness, which in the investigator’s opinion would compromise the participant’s safety or compliance with the study procedures.

12. Participant cannot communicate reliably with the investigator.

13. Participant who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study, or is unlikely to complete the full course of vaccination and observation.

14. Stage 1: Participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19a,13 , ie, participants with moderate-to-severe asthma; chronic lung diseases such as chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), idiopathic pulmonary fibrosis and cystic fibrosis; diabetes (including type 1, type 2, or gestational); serious heart conditions, including heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and (pulmonary) moderate to severe hypertension; high blood pressure; obesity (body mass index (BMI) ≥30 kg/m2 ); chronic liver disease, including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions (dementia); end stage renal disease; organ transplantation; cancer; uncontrolled HIV infection and other immunodeficiencies; hepatitis B infection; sleep apnea; Parkinson’s disease; seizures; ischemic strokes; Intracranial hemorrhage; Guillain-Barré syndrome; encephalopathy; meningoencephalitis; and participants who live in nursing homes or long-term care facilities.

15. Stage 1: Participant has a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or other malignancies with minimal risk of recurrence).

16. Stage 1: Participant has a history of acute polyneuropathy (eg, Guillain-Barré syndrome).

17. Stage 1: Participant had surgery requiring hospitalization (defined as inpatient stay for longer than 24 hours or overnight stay), within 12 weeks before 1st vaccination, or will not have fully recovered from surgery requiring hospitalization, or has surgery requiring hospitalization planned during the time the participant is expected to participate in the study or within 6 months after the last study vaccine administration.

18. Stage 1: Participant has chronic active hepatitis B or hepatitis C infection per medical history. Note: Investigators should ensure that all study enrolment criteria have been met prior to the 1st dose of study vaccine. If a participant’s clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the 1st dose of study vaccine is given such that he or she no longer meets all eligibility criteria, then the participant should be excluded from participation in the study. Section 5.4 describes options for retesting. The required documentation to support meeting the enrolment criteria is described under Source Documents in Appendix 3.

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.

This study is looking to recruit 6,000 individuals and estimates that 14,000 emails are required to be sent by NHS Digital in the first instance to work towards meeting this target.

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 Janssen-Cilag 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 Janssen-Cilag 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 Janssen-Cilag 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 Janssen-Cilag 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 Janssen-Cilag 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, Janssen-Cilag Limited have an appropriate data processing agreement in place with IQVIA LTD to support the recruitment into the trial under Janssen-Cilag’s controllership.

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

Janssen-Cilag 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 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.