A Study on the Safety and Immune Response of Investigational COVID-19 mRNA Vaccines in Healthy Adults

A Phase 2 Randomized, Active-controlled, Observer-blind Study to Assess the Safety, Reactogenicity, and Immunogenicity of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults Who Previously Received a Complete Primary Vaccination Series With or Without Booster Dose(s)

The purpose of Part A of this study is to assess the immune response and safety of a booster dose of investigational COVID-19 mRNA vaccines in healthy adults. The study will compare the investigational vaccines to control vaccine.

The purpose of Part B of this study is to assess the immune response and safety of a booster dose of investigational COVID-19 mRNA vaccines in healthy adults. The study will compare the investigational vaccine under three different storage conditions.

Part A:

This Phase 2 study's Part A evaluates the safety, reactogenicity, and immunogenicity of two candidate vaccines - the bivalent CV0701 and the monovalent CV0601 - in healthy adults who have received a full primary vaccination series (with or without booster doses). By including these candidates, the study will assess whether immune interference occurs between the XY spike protein and the XX spike protein antigens in the bivalent vaccine compared with the XX spike protein antigen in the monovalent vaccine. In Part A, both CV0701 and CV0601 will be compared to the Control Vaccine (that serve as a standard of care control) using a randomized, observer-blinded design.

Part B:

The purpose of Part B is to evaluate the safety and Day 29 immunogenicity of CV0801 under three storage conditions:

• Condition 1: Baseline/control
• Condition 2: Intermediate storage
• Condition 3: Maximum storage

Condition 1 serves as the control against which the performance (safety, reactogenicity, and immunogenicity) of Conditions 2 and 3 will be compared.

mRNA vaccine stability is affected by product-specific factors (e.g., molecular weight, buffer composition, lipid nanoparticle encapsulation), manufacturing factors (such as the duration the vaccine remains in liquid form during production and handling at different temperatures), and storage conditions. The impact of these factors is based on product and process knowledge as well as clinical experience.

Through Part B of this Phase 2 study, GSK and CureVac aim to develop data on how different storage conditions affect the final attributes of the vaccine in a clinical trial setting.

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Is at least 18 years old and has achieved legal age according to local regulations in each participating country.

2. Must provide documented informed consent prior to any study procedures being performed.

3. Can and will comply with the requirements of the protocol, in the opinion of the investigator.

4. Is healthy or medically stable as determined by the investigator's judgment based on medical history, vital sign measurements, and physical examination findings. Participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.

5. Prior receipt of an mRNA COVID-19 vaccine. This may be from a completed primary vaccination series or booster dose(s) of an approved or authorized mRNA COVID-19 vaccine. The last vaccination must be an mRNA COVID-19 vaccination received at least 3 months prior to randomization.

6. If the participant is a woman of childbearing potential, the participant may be enrolled in the study, if they:

   • have practiced adequate contraception for 30 days prior to study intervention administration; and
   • have a negative pregnancy test result on the day of study intervention administration; and
   • have agreed to continue adequate contraception for 2 months after study intervention administration.

Female participants of non-childbearing potential may be enrolled in the study. Nonchildbearing potential is defined as current salpingectomy, hysterectomy, ovariectomy, or postmenopausal.

Participants are excluded from the study if any of the following criteria apply:

1. Is pregnant or has a positive pregnancy test result at Visit 1.
2. Is breastfeeding or will (re)start breastfeeding from the study intervention administration to 3 months after study intervention administration.
3. Has any medical disease or psychiatric condition that, in the opinion of the investigator, precludes study participation because it would place the participant at an unacceptable risk of injury, would render them unable to meet the requirements of the protocol or may interfere with successful completion of the study.
4. Has any history of an immunosuppressive or immunodeficient condition resulting from disease.
5. Has used immunosuppressants or other immune-modifying drugs for 14 consecutive days or more within 3 months prior to the study intervention administration. Non-systemic corticosteroids are allowed. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration.
6. Has an acute medical illness or acute febrile illness with oral temperature ≥38.0°C or ≥100.4°F within 72 hours prior to study intervention administration.
7. Has participated in another study involving any investigational product, vaccine, or device within 28 days before the study intervention administration and/or planned participation through end of study (EoS).
8. Has participated in Part A of this study.
9. Has a history of hypersensitivity or severe allergic reaction including anaphylaxis, generalized urticaria, angioedema, and other significant reactions to any previous mRNA vaccine or any component of the study intervention(s).
10. Has received or plans to receive immunoglobulins or any blood or blood products within 3 months before study intervention administration through EoS.
11. Has a bleeding disorder, or prior history of significant bleeding or bruising following intramuscular injections.
12. Has a history of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
13. Has a history of myocarditis, pericarditis, or idiopathic cardiomyopathy, or presence of any medical condition that increases risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis and persistent myocardial infection.
14. Has received a live vaccine 30 days before the study intervention administration or has a planned administration within 30 days after the study intervention administration.
15. Has received a non-replicating vaccine 8 days before the study intervention administration or has a planned administration within 14 days after the study intervention administration.
16. Has a documented history of confirmed SARS-CoV-2 infection within 3 months before study intervention administration.
17. Has had known close contact with anyone who had a confirmed SARS-CoV-2 infection within 2 weeks before study intervention administration.
18. Is an employee or family member of the investigator or study site staff.