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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NovaDigm Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01926028
First received: August 9, 2013
Last updated: May 27, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Vulvovaginal Candidiasis
Biological: NDV-3A
Biological: NDV-3
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by NovaDigm Therapeutics, Inc.:

Primary Outcome Measures:
  • Safety and tolerability over the 12-months post vaccination period [ Time Frame: 12-month ] [ Designated as safety issue: Yes ]
    Number of vaccine-related adverse events over the 12-months post-vaccination period in the NDV-3A vaccine group, the NDV-3 vaccine group, and the placebo group.


Secondary Outcome Measures:
  • Recurrence of VVC over the 6-month post-vaccination period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Recurrence of VVC due to Candida albicans in women with documented RVVC over the 6-month post-vaccination period in the NDV-3A vaccine group and the placebo group

  • Humoral immune response over the 12-month post-vaccination period [ Time Frame: 12-months ] [ Designated as safety issue: No ]
    Serum anti-Als3 antibody 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.

  • Cellular immune response over the 12-month post-vaccination period [ Time Frame: 12-months ] [ Designated as safety issue: No ]
    Als3-specific T-cell responses 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.


Other Outcome Measures:
  • Recurrence of VVC over the 12-month post-vaccination period [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Recurrence of VVC due to Candida albicans in women with documented RVVC 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 0 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Time-to-onset of first VVC episode from Study Day 0, the day of vaccination, for the NDV-3A vaccine group and the placebo group

  • Severity of VVC episodes over the 12-month post-vaccination period [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Severity of VVC episodes over the 12-month post-vaccination period based on the VVC Signs and Symptoms Questionnaire in the NDV-3A vaccine group and the placebo group


Enrollment: 188
Study Start Date: July 2013
Estimated Study Completion Date: May 2016
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01926028

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

Additional Information:
No publications provided

Responsible Party: NovaDigm Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01926028     History of Changes
Other Study ID Numbers: NDV3A-003
Study First Received: August 9, 2013
Last Updated: May 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by NovaDigm Therapeutics, Inc.:
recurrent vulvovaginal candidiasis
candida
NDV3
vaginal thrush
chronic yeast infection

Additional relevant MeSH terms:
Candidiasis
Candidiasis, Vulvovaginal
Genital Diseases, Female
Mycoses
Vaginal Diseases
Vaginitis
Vulvar Diseases
Vulvitis
Vulvovaginitis
Aluminum Hydroxide
Adjuvants, Immunologic
Antacids
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 27, 2015