Assessing the Safety, Immune Response, and Early Efficacy of a Candida Vaccine in Women With Recurrent Vulvovaginal Candidiasis: A Randomized Controlled Study

Candi5V01 A FTIH Phase I/II Randomized and Controlled Study to Test Safety, Immunogenicity and Preliminary Efficacy of a Pentavalent Bioconjugate Vaccine (Candi5V) Against Candida in Women With Recurrent Vulvovaginal Candidiasis.

In this study, the pentavalent bioconjugate candidate vaccine (Candi5V) against Candida will be tested to obtain first-time-in-human (FTIH) data on its safety, immunogenicity, and preliminary efficacy in women with recurrent vulvovaginal candidiasis.

This is a First Time In Human (FTIH), phase I/II, double-blind, randomized, placebo-controlled study to evaluate the safety, immunogenicity and preliminary efficacy of the candidate pentavalent bioconjugate vaccine (Candi5V), administered twice, 2 months apart, with or without adjuvant.

The study will be conducted in two subsequent steps:

Step 1 (safety cohort): staggered enrolment of small groups of women with history of RVVC, sequentially administered with the half dose of Candi5V non-adjuvanted and with adjuvant or placebo, followed by groups administered with the target dose of Candi5V non-adjuvanted and with adjuvant or placebo.

Step 2 (target cohort): concurrent enrolment of women with history of RVVC, randomized 1:1:1 to Candi5V, Candi5V + adjuvant and placebo.

All study participants will be followed for 12 months after the second vaccination, to assess the vaccine safety profile, the immunological response and the recurrence of any VVC episode.

Inclusion Criteria:

1. Good general health by medical history, laboratory findings and physical examination before receiving vaccination as judged by the Investigator.

2. Documented history of R-VVC, defined as 3 or more VVC episodes in the previous year, of which:

   1. at least 3 can be documented by a visit at a physician's office OR are documented by antifungal drug use as proven by a retrospective pharmacist drug delivery list, or electronic prescription by a physician
   2. at least one is culture OR microscopy confirmed (Pap smear, wet mount or Gram stain for Candida spp).

   Note: patients on chronic long-term treatment with documented RVVC diagnosis with at least 3 VVC episodes within the previous 3 years before enrolment, of which:

   1. at least 3 can be documented by a visit at a physician's office OR are documented by antifungal drug use as proven by a retrospective pharmacist drug delivery list, or electronic prescription by a physician
   2. at least one is culture OR lab-based microscopy confirmed for Candida spp (Pap smear, wet mount or Gram stain).

   may also be considered eligible if not on any antifungal treatment for at least 1-month preceding vaccination.

3. Participant who is willing and able to comply with the requirements of the protocol (e.g., completion of the study diary, return for follow-up visits).

4. Signed written informed consent obtained from the participant.

5. Females between 18-47 years (inclusive) of age at the time of the first vaccination practicing highly effective birth control from prior to first vaccination until at least 28 days after the last vaccination agreed by participants. Females between 48-50 years (inclusive) can be included if they are using combined (estrogen and progesteron containing) hormonal oral contraceptives from prior to first vaccination until at least 1 month after the last vaccination as agreed by participants.

Note: highly effective birth control is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined (estrogen and progesteron containing) hormonal contraceptives associated with inhibition of ovulation (oral or intravaginal or transdermal); progesteron-only hormonal contraceptives associated with inhibition of ovulation (oral or injectable or implantable); intrauterine device; intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; sexual abstinence; vasectomized partner (male partner sterilisation at least 6 months prior to the female participant's entry into the study, and if the relationship is monogamous.

Exclusion Criteria:

1. Health condition that, in the opinion of the Investigator, may interfere with optimal participation in the study or place the participant at increased risk of adverse events.
2. Acute disease including VVC-symptoms at the time of vaccination.
3. Any deviation from the normal range in biochemistry or haematology blood tests or urine safety laboratory clinically significant in the opinion of the Investigator.
4. Clinically significant abnormalities on physical examination.
5. Suspected or known hypersensitivity (including allergy) to any of the medicinal products or medical equipment whose use is foreseen in this study.
6. History of allergy to any vaccine.
7. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws (e.g., coagulation disorder).
8. VVC therapy within 1 month preceding the 1st vaccination (participants meeting this criterion will be followed and may be re-screened at a later timepoint following a negative culture).
9. Participants with cervical diseases, or any other vulvovaginal conditions that may influence vaccine efficacy and VVC treatment.
10. Known or suspected impairment of immunological function, documented Human Immunodeficiency Virus (HIV) infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder.
11. Positive blood test for HBsAg, HCV, HIV-1/2.
12. History of systemic administration of immunosuppressive drugs, i.e., corticosteroids, (PO/IV/IM) within the last month prior to 1st vaccination or for more than 14 consecutive days within 3 months prior to 1st vaccination, until the last blood sampling visit (i.e., prednisone or equivalent ≥20 mg/day). Inhaled and topical steroids are allowed.
13. Administration of antineoplastic and immune-modulating agents or chemotherapy within 3 months prior to informed consent.
14. Planned or actual administration of any licensed vaccine within 14 days prior to each vaccination and 30 days after each vaccination. Note: In case an emergency mass vaccination for an unforeseen public health threat is organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary, for that vaccine provided it is licensed and used according to the local governmental recommendations and provided a written approval of the Sponsor is obtained.
15. Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational interventional vaccine/product (pharmaceutical product).
16. Body Mass Index (BMI) ≤19 and ≥30.
17. History of any chronic or progressive disease that according to judgment of the Investigator could interfere with the study outcomes or pose a threat to the participant's health.
18. Received an investigational or non-registered product (medicinal drug or vaccine), other than the study vaccine within 3 months prior to 1st administration of study vaccine, or planned use during the study period.
19. Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine.
20. Blood donation equal or greater to 500 mL of blood drawn within 3 months preceding the first vaccination or planned during the study period as reported by the participant.
21. Use of any systemic antibiotic therapy within 1 week preceding each vaccination.
22. Participants with an elective surgical intervention, planned during the study period until 28 days after 2nd vaccination.
23. Females lactating, pregnant, or intending to become pregnant as reported by the participant, within at least one month post second vaccination. Note: in case of unintended and unknown pregnancy from prior to first vaccination until at least 1 month after the last vaccination, pregnancy should be followed to term, any premature terminations should be reported, and the health status of the mother and child including date of delivery and the child's gender and weight should be reported after delivery.
24. Current and/or history of chronic alcohol consumption and/or drug abuse.
25. History of immune-mediated disease.