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

NCT ID: NCT01926028

Last Updated: 2018-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2016-05-31

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.

Conditions

Vulvovaginal Candidiasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

NDV-3A

Experimental Vaccine: a purified, recombinant antigen (rAls3) formulated with aluminum hydroxide adjuvant

Group Type: EXPERIMENTAL

NDV-3A

Intervention Type: BIOLOGICAL

0.5mL injection IM

NDV-3

Experimental Vaccine: a purified, recombinant antigen (rAls3 with 6-His tag) formulated with aluminum hydroxide adjuvant

Group Type: EXPERIMENTAL

NDV-3

Intervention Type: BIOLOGICAL

0.5mL injection IM

Placebo

Placebo: aluminum hydroxide adjuvant

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

aluminum hydroxide and buffered saline

Interventions

NDV-3A

0.5mL injection IM

Intervention Type: BIOLOGICAL

NDV-3

0.5mL injection IM

Intervention Type: BIOLOGICAL

Placebo

aluminum hydroxide and buffered saline

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NovaDigm Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John P. Hennessey, Jr., Ph.D.

Role: STUDY_DIRECTOR

NovaDigm Therapeutics, Inc.

Locations

Precision Trials LLC

Phoenix, Arizona, United States

Arkansas Women's Center

Little Rock, Arkansas, United States

Women's Health Care Research Corp

San Diego, California, United States

McCann MD Research, Inc.

Torrance, California, United States

Women's Medical Research Group, LLC

Clearwater, Florida, United States

KO Clinical Research, LLC

Fort Lauderdale, Florida, United States

Miami Clinical Research, LLC

Miami, Florida, United States

Community Medical Research

Miami Beach, Florida, United States

Community Medical Research LLC

North Miami, Florida, United States

MedPharmics

Metairie, Louisiana, United States

WSU Physician's Group

Detroit, Michigan, United States

Saginaw Valley Medical Research Group, LLC

Saginaw, Michigan, United States

Lawrence OB/Gyn Clinical Research

Lawrenceville, New Jersey, United States

SUNY Downstate Medical Center

Brooklyn, New York, United States

Suffolk Ob/Gyn

Port Jefferson, New York, United States

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Magnolia OB/GYN Research Center, LLC

Myrtle Beach, South Carolina, United States

Advanced Research Associates

Corpus Christi, Texas, United States

Discovery Clinical Trials- HCWC, LLC

Dallas, Texas, United States

TMC Life Research

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29697768 (View on PubMed)

Other Identifiers

NDV3A-003

Identifier Type: -

Identifier Source: org_study_id