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

Vulvovaginal Candidiasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01926028
• Other study ID #: NDV3A-003
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2013
• Est. completion date: May 2016

Study information

• Verified date: June 2018
• Source: NovaDigm Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: May 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Candidiasis
• Candidiasis, Vulvovaginal
• Vulvovaginal Candidiasis

Intervention

Biological:
• NDV-3A
0.5mL injection IM
• NDV-3
0.5mL injection IM
• Placebo
aluminum hydroxide and buffered saline

Locations

Country	Name	City	State
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Women's Medical Research Group, LLC	Clearwater	Florida
United States	Advanced Research Associates	Corpus Christi	Texas
United States	Discovery Clinical Trials- HCWC, LLC	Dallas	Texas
United States	WSU Physician's Group	Detroit	Michigan
United States	KO Clinical Research, LLC	Fort Lauderdale	Florida
United States	TMC Life Research	Houston	Texas
United States	Lawrence OB/Gyn Clinical Research	Lawrenceville	New Jersey
United States	Arkansas Women's Center	Little Rock	Arkansas
United States	MedPharmics	Metairie	Louisiana
United States	Miami Clinical Research, LLC	Miami	Florida
United States	Community Medical Research	Miami Beach	Florida
United States	Magnolia OB/GYN Research Center, LLC	Myrtle Beach	South Carolina
United States	Community Medical Research LLC	North Miami	Florida
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Precision Trials LLC	Phoenix	Arizona
United States	Suffolk Ob/Gyn	Port Jefferson	New York
United States	Saginaw Valley Medical Research Group, LLC	Saginaw	Michigan
United States	Women's Health Care Research Corp	San Diego	California
United States	McCann MD Research, Inc.	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
NovaDigm Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12-month
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	12 months
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	12 months
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	12 months
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	12 months
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 28, 90, 180 and 360 days
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.	0, 14, 90 days
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.	0, 14, 90 days

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