Vulvovaginal Candidiasis
Conditions
Keywords
recurrent vulvovaginal candidiasis, candida, NDV3, vaginal thrush, chronic yeast infection
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled study intended to assess the safety, tolerability and humoral and cellular immune response over a 12-month period after receiving one dose of either the NDV-3A vaccine, NDV-3 vaccine, or placebo. In addition, the clinical efficacy of NDV-3A vaccine in lowering the recurrence rate of vulvovaginal candidiasis (VVC) in patients with recurrent VVC (RVVC) will be evaluated relative to placebo.
Detailed description
The purpose of the Phase 1b portion of this study is to compare the NDV-3A vaccine, the NDV-3 vaccine and the placebo head-to-head in the patient population of interest (women with RVVC) to evaluate safety and immunogenicity. The study size for comparing safety and immunogenicity (N=15 per group) is based on the dose comparison design used in study NDV3-001 (clinical trials.gov Identifier NCT01273922). The primary purpose of the Phase 2a portion of this study is to further evaluate safety, tolerability, and immunogenicity of the NDV-3A vaccine compared to placebo in a patient population of interest (women with RVVC). The secondary purpose is to determine whether the NDV-3A vaccine decreases the recurrence rate of VVC in 18-50 year old women with RVVC when compared to placebo. The study size for evaluating efficacy (N=87 per group) is based on assuming a 50% rate of VVC recurrences over the 6 month post-vaccination period in the placebo group and a 50% vaccine efficacy.
Interventions
BIOLOGICALNDV-3A
0.5mL injection IM
BIOLOGICALNDV-3
0.5mL injection IM
BIOLOGICALPlacebo
aluminum hydroxide and buffered saline
Sponsors
NovaDigm Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Has been informed of the nature of the study and has agreed to and is able to read, review, and sign the informed consent document prior to Screening. * Is a female between 18-50 years of age, inclusive, at the time of vaccination on an acceptable form of birth control. * Has a current episode of VVC (at Screening/Day -14) that can be confirmed with acute signs and symptoms of VVC (Composite Questionnaire score of ≥3) and a positive vaginal mycological culture for C. albicans. * Has a history of 2 or more documented episodes of VVC in the 12 months prior to Screening, including at least one of the previous episodes confirmed by positive results from a diagnostic lab test specific for the presence of Candida. Additional episodes may be self-reported. * Has a normal Papanicolaou (Pap) smear from the previous 12 months, or has no clinically significant abnormalities on a Pap smear taken at study entry as judged and documented by the investigator(s). * Is in general good health as judged and documented by the investigator(s)
Exclusion criteria
* Reports receiving any systemic or topical vaginal antifungal therapy for 4 weeks prior to study entry. * Mycological results from Study Day -14 or earlier cultures taken within 4 weeks prior to vaccination that show other yeast species (e.g., C. glabrata, C. tropicalis, etc.) as the cause of vaginitis. * Has other active infectious cause(s) of vulvovaginitis (e.g., bacterial vaginosis, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea, symptomatic Herpes Simplex Virus-1 (HSV-1), symptomatic HSV-2, or symptomatic human papilloma virus) at Screening or other vaginal or vulvar conditions that would confound the interpretation of clinical response as judged by the investigator(s). * Will be under treatment or surgery at the start of the study for cervical intraepithelial neoplasia (CIN) or cervical carcinoma. * Reports any presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s), diagnosed diabetes mellitus (controlled or not) or psychiatric disease that would confound the interpretation of clinical response as judged by the investigator(s). * Reports a history of allergic response(s) or other serious reactions to nickel, aluminum, or yeast products * Reports a history of clinically significant allergies including food or drug allergies, anaphylaxis (or other serious reaction) to vaccines. * Has a known history of or active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). * Reports receiving or planning to receive any investigational drug, investigational vaccine, or investigational device within 4 weeks prior to vaccination, and at any other time during their participation in the study. * Reports receiving or planning to receive any other live vaccine within 3 weeks prior to vaccination and for 3 weeks after vaccination. * Reports having or shows evidence of a recent history of drug or alcohol abuse. * Reports the use or planned use of any immunosuppressive drugs, including systemic or topical vaginal corticosteroids, within 4 weeks prior to vaccination, with the exception of topical steroids (e.g., Over-The-Counter hydrocortisone) used elsewhere on the body. * Reports the use or planned use of any medications or treatments that may alter immune responses to the study vaccine within 3 weeks prior to vaccination * Reports receiving any blood products within 3 months prior to vaccination and throughout the study. * Reports donating blood/plasma within 4 weeks prior to vaccination. * Is pregnant or intends to become pregnant over the course of the study, breastfeeding, or has any other medical and/or social (e.g., non-compliant) reason which, in the opinion of the investigator(s), would prevent participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | 12-month | Summary of injection site reactions for the safety population over the 12-months post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Were Recurrence-free Over the 12-month Post-vaccination Period | 12 months | Number of patients with documented RVVC who were recurrence-free over the 12-month post-vaccination period in the NDV-3A vaccine group and the placebo group |
| Time to First VVC Episode From Study Day 17 to 360 - Participants <40 Years Old | 12 months | Time-to-onset of first VVC episode from Study Day 17 for the NDV-3A vaccine group and the placebo group |
| Time to First VVC Episode From Study Day 17 to 360 - All Participants | 12 months | Time-to-onset of first VVC episode from Study Day 17 for the NDV-3A vaccine group and the placebo group |
| Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | 0, 14, 28, 90, 180 and 360 days | Serum anti-Als3 IgG titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
| Number of Patients <40 Years Old Who Were Recurrence-free Over the 12-month Post-vaccination Period | 12 months | Number of patients \<40 years old with documented RVVC who were recurrence-free over the 12-month post-vaccination period in the NDV-3A vaccine group and the placebo group |
| Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | 0, 14, 28, 90, 180 and 360 days | Cervicovaginal wash anti-Als3 IgG titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
| Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | 0, 14, 28, 90, 180 and 360 days | Cervicovaginal wash anti-Als3 IgA1 titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
| Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | 0, 14, 90 days | Als3-specific T-cell production of interferon gamma will be measured by enzyme-linked immunospot (ELISpot) at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
| Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | 0, 14, 90 days | Als3-specific T-cell production of interleukin-17A will be measured by enzyme-linked immunospot (ELISpot) at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
| Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | 0, 14, 28, 90, 180 and 360 days | Serum anti-Als3 IgA1 titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: aluminum hydroxide adjuvant
Placebo: 0.5 mL injection IM | 85 |
| NDV-3A Experimental Vaccine: a purified, recombinant antigen (rAls3) formulated with aluminum hydroxide adjuvant
NDV-3A: 0.5mL injection IM | 89 |
| NDV-3 Experimental Vaccine: a purified, recombinant antigen (rAls3 with 6-His tag) formulated with aluminum hydroxide adjuvant
NDV-3: 0.5mL injection IM | 14 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 6 | 0 |
| Overall Study | Non compliance or other reasons | 4 | 2 | 0 |
| Overall Study | Physician Decision | 1 | 5 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 9 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | NDV-3 | NDV-3A |
|---|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 8.8 | 32.5 years STANDARD_DEVIATION 8.95 | 35.4 years STANDARD_DEVIATION 10.7 | 32.1 years STANDARD_DEVIATION 8.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 66 Participants | 3 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 122 Participants | 11 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 38 Participants | 2 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 64 Participants | 144 Participants | 12 Participants | 68 Participants |
| Region of Enrollment United States | 85 Participants | 188 Participants | 14 Participants | 89 Participants |
| Sex: Female, Male Female | 85 Participants | 188 Participants | 14 Participants | 89 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 89 | 0 / 14 |
| other Total, other adverse events | 48 / 85 | 35 / 89 | 3 / 14 |
| serious Total, serious adverse events | 0 / 85 | 0 / 89 | 0 / 14 |
Outcome results
Primary
Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period
Summary of injection site reactions for the safety population over the 12-months post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 12-month
Population: All enrolled patients.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Placebo | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Pain | 56 AEs |
| Placebo | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Tenderness | 64 AEs |
| Placebo | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Redness | 34 AEs |
| Placebo | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Induration | 25 AEs |
| Placebo | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Patients with >= 1 injection site reaction | 72 AEs |
| Placebo | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Swelling | 28 AEs |
| NDV-3A | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Patients with >= 1 injection site reaction | 79 AEs |
| NDV-3A | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Induration | 46 AEs |
| NDV-3A | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Pain | 70 AEs |
| NDV-3A | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Redness | 45 AEs |
| NDV-3A | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Swelling | 47 AEs |
| NDV-3A | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Tenderness | 71 AEs |
| NDV-3 | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Induration | 0 AEs |
| NDV-3 | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Tenderness | 10 AEs |
| NDV-3 | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Swelling | 2 AEs |
| NDV-3 | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Pain | 7 AEs |
| NDV-3 | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Patients with >= 1 injection site reaction | 10 AEs |
| NDV-3 | Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period | Redness | 2 AEs |
Secondary
Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period
Als3-specific T-cell production of interferon gamma will be measured by enzyme-linked immunospot (ELISpot) at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 0, 14, 90 days
Population: All participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 14 | 3.0 Spot Forming Units | Standard Deviation 3.2 |
| Placebo | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 0 | 2.7 Spot Forming Units | Standard Deviation 3 |
| Placebo | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 90 | 3.2 Spot Forming Units | Standard Deviation 3.5 |
| NDV-3A | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 14 | 22.8 Spot Forming Units | Standard Deviation 5.3 |
| NDV-3A | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 0 | 3.6 Spot Forming Units | Standard Deviation 3.3 |
| NDV-3A | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 90 | 16.6 Spot Forming Units | Standard Deviation 4.6 |
| NDV-3 | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 0 | 2.6 Spot Forming Units | Standard Deviation 3.4 |
| NDV-3 | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 90 | 15.1 Spot Forming Units | Standard Deviation 4.9 |
| NDV-3 | Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period | Day 14 | 22.1 Spot Forming Units | Standard Deviation 7.7 |
Secondary
Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period
Als3-specific T-cell production of interleukin-17A will be measured by enzyme-linked immunospot (ELISpot) at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 0, 14, 90 days
Population: All Participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 14 | 2.6 Spot Forming Units | Standard Deviation 3.4 |
| Placebo | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 0 | 3.4 Spot Forming Units | Standard Deviation 4.1 |
| Placebo | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 90 | 2.9 Spot Forming Units | Standard Deviation 3.5 |
| NDV-3A | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 14 | 9.6 Spot Forming Units | Standard Deviation 5.3 |
| NDV-3A | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 0 | 4.2 Spot Forming Units | Standard Deviation 4.4 |
| NDV-3A | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 90 | 6.6 Spot Forming Units | Standard Deviation 3.9 |
| NDV-3 | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 0 | 5.2 Spot Forming Units | Standard Deviation 4.1 |
| NDV-3 | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 90 | 3.3 Spot Forming Units | Standard Deviation 3.7 |
| NDV-3 | Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period | Day 14 | 11.1 Spot Forming Units | Standard Deviation 5.4 |
Secondary
Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period
Cervicovaginal wash anti-Als3 IgA1 titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 0, 14, 28, 90, 180 and 360 days
Population: All participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 0 | 4.86 Titer (dilution^-1) | Standard Deviation 6.37 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 14 | 4.99 Titer (dilution^-1) | Standard Deviation 7.89 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 28 | 3.44 Titer (dilution^-1) | Standard Deviation 4.51 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 90 | 2.87 Titer (dilution^-1) | Standard Deviation 4.89 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 180 | 3.13 Titer (dilution^-1) | Standard Deviation 5.6 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 360 | 3.39 Titer (dilution^-1) | Standard Deviation 5.05 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 360 | 9.32 Titer (dilution^-1) | Standard Deviation 7.06 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 0 | 5.16 Titer (dilution^-1) | Standard Deviation 5.38 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 90 | 22.52 Titer (dilution^-1) | Standard Deviation 7.5 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 180 | 17.74 Titer (dilution^-1) | Standard Deviation 5.76 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 14 | 53.65 Titer (dilution^-1) | Standard Deviation 7 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 28 | 45.96 Titer (dilution^-1) | Standard Deviation 8.56 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 14 | 28.24 Titer (dilution^-1) | Standard Deviation 6.86 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 28 | 22.22 Titer (dilution^-1) | Standard Deviation 9.61 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 360 | 5.02 Titer (dilution^-1) | Standard Deviation 7.41 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 90 | 5.75 Titer (dilution^-1) | Standard Deviation 6 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 0 | 2.02 Titer (dilution^-1) | Standard Deviation 6.81 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 180 | 10.17 Titer (dilution^-1) | Standard Deviation 4.83 |
Secondary
Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period
Cervicovaginal wash anti-Als3 IgG titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 0, 14, 28, 90, 180 and 360 days
Population: All participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 0 | 2.03 Titer (dilution^-1) | Standard Deviation 5.27 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 14 | 1.93 Titer (dilution^-1) | Standard Deviation 5.15 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 28 | 1.44 Titer (dilution^-1) | Standard Deviation 3.63 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 90 | 1.40 Titer (dilution^-1) | Standard Deviation 3.97 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 180 | 1.66 Titer (dilution^-1) | Standard Deviation 4.55 |
| Placebo | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 360 | 1.44 Titer (dilution^-1) | Standard Deviation 5.14 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 360 | 4.36 Titer (dilution^-1) | Standard Deviation 6.39 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 0 | 1.93 Titer (dilution^-1) | Standard Deviation 4.19 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 90 | 14.28 Titer (dilution^-1) | Standard Deviation 6.16 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 180 | 7.68 Titer (dilution^-1) | Standard Deviation 6.73 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 14 | 20.67 Titer (dilution^-1) | Standard Deviation 6.28 |
| NDV-3A | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 28 | 24.98 Titer (dilution^-1) | Standard Deviation 6.97 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 14 | 8.01 Titer (dilution^-1) | Standard Deviation 8.09 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 28 | 9.88 Titer (dilution^-1) | Standard Deviation 14.49 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 360 | 2.76 Titer (dilution^-1) | Standard Deviation 6.12 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 90 | 5.28 Titer (dilution^-1) | Standard Deviation 4.11 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 0 | 1.47 Titer (dilution^-1) | Standard Deviation 4.69 |
| NDV-3 | Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 180 | 2.72 Titer (dilution^-1) | Standard Deviation 6.42 |
Secondary
Number of Patients <40 Years Old Who Were Recurrence-free Over the 12-month Post-vaccination Period
Number of patients \<40 years old with documented RVVC who were recurrence-free over the 12-month post-vaccination period in the NDV-3A vaccine group and the placebo group
Time frame: 12 months
Population: Participants \<40 years old
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients <40 Years Old Who Were Recurrence-free Over the 12-month Post-vaccination Period | 11 Participants |
| NDV-3A | Number of Patients <40 Years Old Who Were Recurrence-free Over the 12-month Post-vaccination Period | 24 Participants |
p-value: 0.0395% CI: [0.17, 0.91]Wilcoxon (Mann-Whitney)
Secondary
Number of Patients Who Were Recurrence-free Over the 12-month Post-vaccination Period
Number of patients with documented RVVC who were recurrence-free over the 12-month post-vaccination period in the NDV-3A vaccine group and the placebo group
Time frame: 12 months
Population: All participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients Who Were Recurrence-free Over the 12-month Post-vaccination Period | 17 Participants |
| NDV-3A | Number of Patients Who Were Recurrence-free Over the 12-month Post-vaccination Period | 28 Participants |
p-value: 0.195% CI: [0.27, 1.13]Wilcoxon (Mann-Whitney)
Secondary
Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period
Serum anti-Als3 IgA1 titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 0, 14, 28, 90, 180 and 360 days
Population: All participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 14 | 954 Titer (dilution^-1) | Standard Deviation 6.4 |
| Placebo | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 0 | 937 Titer (dilution^-1) | Standard Deviation 5.6 |
| Placebo | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 28 | 850 Titer (dilution^-1) | Standard Deviation 5.5 |
| Placebo | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 90 | 1062 Titer (dilution^-1) | Standard Deviation 6 |
| Placebo | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 180 | 982 Titer (dilution^-1) | Standard Deviation 7.3 |
| Placebo | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 360 | 563 Titer (dilution^-1) | Standard Deviation 7.3 |
| NDV-3A | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 360 | 8727 Titer (dilution^-1) | Standard Deviation 5.8 |
| NDV-3A | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 180 | 18215 Titer (dilution^-1) | Standard Deviation 5.9 |
| NDV-3A | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 0 | 1011 Titer (dilution^-1) | Standard Deviation 5.5 |
| NDV-3A | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 90 | 23053 Titer (dilution^-1) | Standard Deviation 5.1 |
| NDV-3A | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 14 | 63834 Titer (dilution^-1) | Standard Deviation 5.1 |
| NDV-3A | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 28 | 43557 Titer (dilution^-1) | Standard Deviation 5.2 |
| NDV-3 | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 14 | 44866 Titer (dilution^-1) | Standard Deviation 3.7 |
| NDV-3 | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 28 | 30118 Titer (dilution^-1) | Standard Deviation 3.2 |
| NDV-3 | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 360 | 12357 Titer (dilution^-1) | Standard Deviation 3.1 |
| NDV-3 | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 90 | 20349 Titer (dilution^-1) | Standard Deviation 3.1 |
| NDV-3 | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 0 | 657 Titer (dilution^-1) | Standard Deviation 3.1 |
| NDV-3 | Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period | Day 180 | 14633 Titer (dilution^-1) | Standard Deviation 3.4 |
Secondary
Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period
Serum anti-Als3 IgG titers will be measured by ELISA at pre-defined time points over the 12-month post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.
Time frame: 0, 14, 28, 90, 180 and 360 days
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 0 | 465 Titer (dilution^-1) | Standard Deviation 3.3 |
| Placebo | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 14 | 464 Titer (dilution^-1) | Standard Deviation 3.6 |
| Placebo | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 28 | 419 Titer (dilution^-1) | Standard Deviation 3.3 |
| Placebo | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 90 | 447 Titer (dilution^-1) | Standard Deviation 3.2 |
| Placebo | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 180 | 523 Titer (dilution^-1) | Standard Deviation 3.5 |
| Placebo | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 360 | 371 Titer (dilution^-1) | Standard Deviation 3.6 |
| NDV-3A | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 360 | 5349 Titer (dilution^-1) | Standard Deviation 3.2 |
| NDV-3A | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 0 | 434 Titer (dilution^-1) | Standard Deviation 3.5 |
| NDV-3A | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 90 | 17818 Titer (dilution^-1) | Standard Deviation 3.5 |
| NDV-3A | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 180 | 10852 Titer (dilution^-1) | Standard Deviation 3.5 |
| NDV-3A | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 14 | 37381 Titer (dilution^-1) | Standard Deviation 3.9 |
| NDV-3A | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 28 | 31459 Titer (dilution^-1) | Standard Deviation 3.6 |
| NDV-3 | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 14 | 18078 Titer (dilution^-1) | Standard Deviation 4.6 |
| NDV-3 | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 28 | 13674 Titer (dilution^-1) | Standard Deviation 4.6 |
| NDV-3 | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 360 | 4999 Titer (dilution^-1) | Standard Deviation 3.9 |
| NDV-3 | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 90 | 10868 Titer (dilution^-1) | Standard Deviation 3.8 |
| NDV-3 | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 0 | 305 Titer (dilution^-1) | Standard Deviation 3.1 |
| NDV-3 | Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period | Day 180 | 6297 Titer (dilution^-1) | Standard Deviation 3.9 |
Secondary
Time to First VVC Episode From Study Day 17 to 360 - All Participants
Time-to-onset of first VVC episode from Study Day 17 for the NDV-3A vaccine group and the placebo group
Time frame: 12 months
Population: All participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First VVC Episode From Study Day 17 to 360 - All Participants | 135 Days |
| NDV-3A | Time to First VVC Episode From Study Day 17 to 360 - All Participants | 175 Days |
Secondary
Time to First VVC Episode From Study Day 17 to 360 - Participants <40 Years Old
Time-to-onset of first VVC episode from Study Day 17 for the NDV-3A vaccine group and the placebo group
Time frame: 12 months
Population: Participants \< 40 years old
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First VVC Episode From Study Day 17 to 360 - Participants <40 Years Old | 105 Days |
| NDV-3A | Time to First VVC Episode From Study Day 17 to 360 - Participants <40 Years Old | 210 Days |