Safety, Tolerability, Immunogenicity and Efficacy of NDV-3A Vaccine in Preventing Recurrent Vulvovaginal Candidiasis

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

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.

Study Overview

• Status: Completed
• Conditions: Vulvovaginal Candidiasis
• Intervention / Treatment: Biological: NDV-3A; Biological: NDV-3; Biological: 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.

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Precision Trials LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Women's Center
  • California
    • San Diego, California, United States, 92123
      • Women's Health Care Research Corp
    • Torrance, California, United States, 90505
      • McCann MD Research, Inc.
  • Florida
    • Clearwater, Florida, United States, 33759
      • Women's Medical Research Group, LLC
    • Fort Lauderdale, Florida, United States, 33316
      • KO Clinical Research, LLC
    • Miami, Florida, United States, 33155
      • Miami Clinical Research, LLC
    • Miami Beach, Florida, United States, 33141
      • COMMUNITY Medical Research
    • North Miami, Florida, United States, 33181
      • Community Medical Research LLC
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics
  • Michigan
    • Detroit, Michigan, United States, 48201
      • WSU Physician's Group
    • Saginaw, Michigan, United States, 48604
      • Saginaw Valley Medical Research Group, LLC
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrence OB/Gyn Clinical Research
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Port Jefferson, New York, United States, 11777
      • Suffolk OB/GYN
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29752
      • Magnolia Ob/Gyn Research Center, LLC
  • Texas
    • Corpus Christi, Texas, United States, 78414
      • Advanced Research Associates
    • Dallas, Texas, United States, 75231
      • Discovery Clinical Trials- HCWC, LLC
    • Houston, Texas, United States, 77054
      • TMC Life Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NDV-3A; Experimental Vaccine: a purified, recombinant antigen (rAls3) formulated with aluminum hydroxide adjuvant	Biological: NDV-3A; 0.5mL injection IM
Experimental: NDV-3; Experimental Vaccine: a purified, recombinant antigen (rAls3 with 6-His tag) formulated with aluminum hydroxide adjuvant	Biological: NDV-3; 0.5mL injection IM
Placebo Comparator: Placebo; Placebo: aluminum hydroxide adjuvant	Biological: Placebo; aluminum hydroxide and buffered saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months
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	12 months
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	12 months
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	12 months
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 90 days
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.	0, 14, 90 days

Collaborators and Investigators

• Sponsor: NovaDigm Therapeutics, Inc.
• Investigators: Study Director: John P. Hennessey, Jr., Ph.D., NovaDigm Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Helpful Links

• Company Web Site

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: August 16, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: June 22, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: candida; recurrent vulvovaginal candidiasis; NDV3; vaginal thrush; chronic yeast infection
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Vaginal Diseases; Vulvar Diseases; Vaginitis; Vulvitis; Vulvovaginitis; Candidiasis; Candidiasis, Vulvovaginal
• Other Study ID Numbers: NDV3A-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Presentations at scientific meetings and publication