Clinical trial NCT01926028: Safety, Tolerability, Immunogenicity and Efficacy of NDV-3A Vaccine in Preventing Recurrent Vulvovaginal Candidiasis
Official title: Phase 1b/2a, Multi-center, Double-blind, Randomized, Placebo-controlled Study of a Single Dose of NDV-3A or NDV-3 Vaccine to Evaluate Safety, Tolerability, Immunogenicity and Efficacy in Preventing Recurrent Vulvovaginal Candidiasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Vulvovaginal Candidiasis
Keywords: recurrent vulvovaginal candidiasis
candida
NDV3
vaginal thrush
chronic yeast infection
Lead sponsor: NovaDigm Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-20
Enrollment: 188
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period
timeFrame: 12-month
Secondary outcomes:
measure: Number of Patients <40 Years Old Who Were Recurrence-free Over the 12-month Post-vaccination Period
timeFrame: 12 months
measure: Number of Patients Who Were Recurrence-free Over the 12-month Post-vaccination Period
timeFrame: 12 months
measure: Time to First VVC Episode From Study Day 17 to 360 - Participants <40 Years Old
timeFrame: 12 months
measure: Time to First VVC Episode From Study Day 17 to 360 - All Participants
timeFrame: 12 months
measure: Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period
timeFrame: 0, 14, 28, 90, 180 and 360 days
measure: Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period
timeFrame: 0, 14, 28, 90, 180 and 360 days
measure: Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period
timeFrame: 0, 14, 28, 90, 180 and 360 days
measure: Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period
timeFrame: 0, 14, 28, 90, 180 and 360 days
measure: Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period
timeFrame: 0, 14, 90 days
measure: Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period
timeFrame: 0, 14, 90 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Precision Trials LLC
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Women's Center
state: Arkansas
city: San Diego
country: United States
facility: Women's Health Care Research Corp
state: California
city: Torrance
country: United States
facility: McCann MD Research, Inc.
state: California
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: KO Clinical Research, LLC
state: Florida
city: Miami Beach
country: United States
facility: Community Medical Research
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research, LLC
state: Florida
city: North Miami
country: United States
facility: Community Medical Research LLC
state: Florida
city: Metairie
country: United States
facility: MedPharmics
state: Louisiana
city: Detroit
country: United States
facility: WSU Physician's Group
state: Michigan
city: Saginaw
country: United States
facility: Saginaw Valley Medical Research Group, LLC
state: Michigan
city: Lawrenceville
country: United States
facility: Lawrence OB/Gyn Clinical Research
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Port Jefferson
country: United States
facility: Suffolk Ob/Gyn
state: New York
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Magnolia OB/GYN Research Center, LLC
state: South Carolina
city: Corpus Christi
country: United States
facility: Advanced Research Associates
state: Texas
city: Dallas
country: United States
facility: Discovery Clinical Trials- HCWC, LLC
state: Texas
city: Houston
country: United States
facility: TMC Life Research
state: Texas
Study officials:
affiliation: NovaDigm Therapeutics, Inc.
name: John P. Hennessey, Jr., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Edwards JE Jr, Schwartz MM, Schmidt CS, Sobel JD, Nyirjesy P, Schodel F, Marchus E, Lizakowski M, DeMontigny EA, Hoeg J, Holmberg T, Cooke MT, Hoover K, Edwards L, Jacobs M, Sussman S, Augenbraun M, Drusano M, Yeaman MR, Ibrahim AS, Filler SG, Hennessey JP Jr. A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis. 2018 Jun 1;66(12):1928-1936. doi: 10.1093/cid/ciy185.