Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent VLP Vaccine

A Phase II, Randomized, Controlled, Double-Blind, Dosage and Adjuvant Justification, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Adjuvanted With or Without Monophosphoryl Lipid A and Aluminum Hydroxide in Adults

The purpose of this study is to select the optimal formulation of the norovirus vaccine from different concentrations of virus-like particles (VLP), Aluminum Hydroxide and MPL adjuvant (3-O-desacyl-4'-monophosphoryl lipid A) for further development.

The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine adjuvanted with aluminum hydroxide and with or without monophosphoryl lipid A (MPL). The norovirus vaccine is being tested to assess different formulations of the vaccine that will then be further developed.

This study will look at the number of antibodies to norovirus formed in people who take different formulations of the norovirus vaccine. The study will enroll approximately 420 patients. Participants will be randomly assigned (by chance) to one of fourteen treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need).

All participants will receive a vaccination on Day 1 and Day 28 of the study. Some treatment arms will receive one dose of the norovirus vaccine and some arms will receive two. In order to keep the treatment arms undisclosed to the patient and the doctor, those randomized to the one dose groups will receive a dose of Hepatitis A vaccine on Day 1 followed by the norovirus vaccine 28 days later. Participants will be asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 7 days after each vaccination.

This multi-centre trial will be conducted in Belgium. The overall time to participate in this study is up to 393 days. Participants will make 6 visits to the clinic, and will be contacted by telephone twice for follow-up assessments.

Inclusion Criteria:

1. Male and female participants between 18 and 64 years of age at the time of enrollment.
2. In good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs), and clinical judgment of the investigator.
3. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
4. Can comply with trial procedures and are available for the duration of the trial.

Exclusion Criteria:

1. Has received any vaccines containing Hepatitis A vaccine within the past 5 years.

2. Has contraindications, warnings, and/or precautions to vaccination with Havrix as specified within the Summary of Product Characteristics.

3. Has a clinically significant active infection (as assessed by the investigator) or oral body temperature 38°C (100.4°F) or higher within 3 days of the intended date of vaccination.

4. Has received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.

5. Known hypersensitivity or allergy to investigational vaccine (including excipients of the investigational vaccine).

6. Has behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant's ability to participate in the trial.

7. Has a history of any progressive or severe neurologic disorder, seizure disorder, or Guillain-Barré syndrome.

8. Has history of any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial.

9. Known or inspected impairment/alteration of immune function, including the following:

   1. Chronic use of oral steroids (Equivalent to 20 mg/day prednisone for ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
   2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1.
   3. Receipt of immunostimulants within 60 days prior to Day 1.
   4. Receipt of parenteral, epidural, or intra-articular immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Day 1 or planned during the full length of the trial.
   5. Receipt of immunosuppressive therapy within 6 months prior to Day 1.
   6. Human immunodeficiency virus (HIV) infection or HIV-related disease.
   7. Heritable immunodeficiency.

10. Abnormalities of splenic or thymic function.

11. Has a known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.

12. Has any serious chronic or progressive disease according to judgment of the investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic disease).

13. Has a body mass index (BMI) greater than or equal to 35 kg/m^2 (=weight in kg/[height in meters * height in meters]).

14. Is participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.

15. Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of investigational vaccine administration.

16. Is first degree relatives of individuals involved in trial conduct.

17. Has history of substance or alcohol abuse within the past 2 years.

18. If female, of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to trial entry.

19. Female participants of childbearing potential and sexually active, who refuse to use an acceptable contraceptive method from Day 1 through 6 months after the last dose of investigational vaccine.

20. Female participants who plan to donate ova from Day 1 through 6 months after the last dose of investigational vaccine.

21. Female participants with any positive pregnancy test.

22. Female participants who are pregnant or breastfeeding.