Safety and Immunogenicity Study of the DuoChol Oral Cholera Vaccine in Healthy Participants

A Phase I, Open-label, Randomized, Active-Controlled Trial to Evaluate the Safety and Immunogenicity of the DuoChol Oral Cholera Vaccine in 18 to 45 Years Old Healthy Participants in Sweden

The goal of this phase I, open-label, randomized, active-controlled Trial is to evaluate the safety and immunogenicity of the DuoChol Oral Cholera Vaccine in 18 to 45 years old healthy participants in Sweden. This first-in-human study is intended to obtain initial data on the DuoChol oral cholera vaccine safety and its effect on immune responses in a cholera non-endemic setting to guide future studies in cholera endemic population. The Investigators will evaluate the safety and immunogenicity after each dose vaccination of DuoChol Oral Cholera Vaccine/Dukoral®.

The participants will be randomly assigned to receive 2 vaccinations at 14-day intervals of DuoChol or Dukoral® in a 2:1 ratio. Participants in the DuoChol arm will receive one capsule of DuoChol on days 0 and 14. Participants in the Dukoral® arm will receive the standard dose as indicated in the Dukoral® package insert. The Investigators will follow-up the participants for 4 weeks after the second vaccination.

The study is funded by Wellcome Trust, grant number : 226726/Z/22/Z.

A total of 60 healthy participants aged 18-45 in Sweden will be recruited and randomly assigned in a 2:1 ratio: 40 participants will receive DuoChol, 20 participants will receive Dukoral®. Each person will receive two doses of DuoChol or Dukoral® orally. There participants will have 6 scheduled study visits, including blood sampling for immunogenicity testing and safety assessment.

Blood samples will be taken at screening, and then during the study, to check immune response and overall health status. Baseline tests include HIV, hepatitis, complete blood counts, and liver function test. Women of childbearing age will undergo pregnancy testing during screening and prior to each vaccination.

All participants will be observed after vaccination for immediate reactions. Serious adverse events will be reported, and followed up till resolution, and participants are instructed to contact the Investigator team if they experience any serious adverse event.

Study Objectives:

• Primary: To evaluate the safety after each dose vaccination of DuoChol Oral Cholera Vaccine.
• Secondary: To compare the immune response of DuoChol with the existing vaccine Dukoral® to assess whether DuoChol can generate a response in the immune system to protect against the disease.

Key Endpoints:

• Monitor for any serious adverse events like hospitalization, death, or significant disability that happen during the study that may or may not be related to the vaccines.
• Track immediate reactions within 1-2 hours after vaccination to detect allergic or other immediate responses.
• Record mild to moderate side effects such as nausea, fever, or diarrhea for up to 14 days after each dose.
• Measure immune response in the blood 14 days after each dose.

Inclusion Criteria:

1. Healthy male or female participants aged 18 to 45 years, inclusive, at the time of signing the informed consent.

2. Must have a Swedish (or other nationality) identity card

3. Must be able to understand the information included in the informed consent form and be willing to provide voluntary informed consent to participate in the study

4. Must agree to not take any medication affecting gastric acidity (such as proton pump inhibitor, H2 receptor blocker, or antacid) for 7 days prior to and until 24 hours after each vaccination.

5. Must be able to attend all scheduled study visits and comply with all study procedures.

6. Must be in good general health and without clinically significant medical history, as determined by the study investigator using clinical judgement after review of medical history, physical examination, and laboratory screening tests (hematology, renal function, and liver function tests).

7. Female-Specific Criteria:

   1. Not currently pregnant or breastfeeding and not planning to become pregnant for at least 12 weeks after last vaccination.
   2. Negative urine pregnancy test at the time of vaccination.
   3. Agree to use at least one acceptable an adequate birth control method for at least 4 weeks prior to receipt of vaccine and for at least 12 weeks after receipt of the vaccine. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted underneath the skin, surgical methods (hysterectomy or bilateral tub l ligation), condoms, diaphragms, intrauterine device, or abstinence

8. Male-Specific Criteria:

   1. Be willing to use an adequate birth control method during study participation and 12 weeks after the last vaccination.
   2. For non-vasectomized male participants with female partners of child- bearing potential this includes the use of condoms or abstinence and/or their partner's use of contraceptive medications delivered orally, intramuscularly, vaginally, or implanted underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), diaphragms, or intrauterine device.

Exclusion Criteria:

1. Any clinically significant symptom of acute illness (e.g., cough, sore throat), febrile illness (tympanic temperature >38°C) within 72 hours prior to the enrollment. A prospective participant should not be included until 72 hours after the condition has completely resolved.
2. Participant with diarrhea, abdominal pain or vomiting in the past 24 hours or with history of diarrhea lasting for more than 2 weeks in the past 6 months.
3. Known history of any immunocompromised condition, including immunodeficiency disease, renal function disorder, malignancy, chronic inflammatory disease, etc.
4. Use of systemic steroids within past 6 months (>10 mg/day prednisone equivalent for period exceeding 2 consecutive weeks), or history of having received chemotherapy, radiation therapy or other immunosuppressive drugs within the past 6 months.
5. Participant who has ever received previous immunization with cholera vaccine, who has received any vaccine within 4 weeks prior to the first dose of study vaccination, or who plans to receive any other vaccine within 4 weeks following last dose of the investigational product.
6. Participant concomitantly enrolled or scheduled to be enrolled in another trial.
7. Participant with previous history of confirmed cholera, salmonella, shigella or ETEC disease.
8. Known history or allergy to vaccine components, or any other allergies deemed by the investigator to increase risk of an adverse event during trial participation.
9. Individuals with a known bleeding disorder, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for blood sample collection.
10. Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months.
11. Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant or interfere with the assessment of the study objectives.
12. Any female participant who is lactating*, pregnant, or planning for pregnancy during study period.
13. Individuals who are involved in DuoChol Clinical trial or family/household members of research staff.
14. Any other condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives (e.g., alcohol or drug abuse, neurologic or psychiatric conditions etc.).