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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 40
- 主要终点
- Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
NDV-3
Experimental Vaccine: a purified, recombinant antigen (rAls3 with 6-His tag) formulated with aluminum hydroxide adjuvant
干预措施: NDV-3 (Biological)
NDV-3A
Experimental Vaccine: a purified, recombinant antigen (rAls3) formulated with aluminum hydroxide adjuvant
干预措施: NDV-3A (Biological)
Placebo
Placebo: aluminum hydroxide adjuvant
干预措施: Placebo (Biological)
结局指标
主要结局
Summary of Injection Site Reactions for the Safety Population Over the 12-months Post Vaccination Period
时间窗: 12-month
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.
次要结局
- Time to First VVC Episode From Study Day 17 to 360 - All Participants(12 months)
- Cervicovaginal Wash Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period(0, 14, 28, 90, 180 and 360 days)
- Als3-specific T-cell Production of Interferon Gamma Over the Post-vaccination Period(0, 14, 90 days)
- Als3-specific T-cell Production of Interleukin-17A Over the Post-vaccination Period(0, 14, 90 days)
- Number of Patients Who Were Recurrence-free Over the 12-month Post-vaccination Period(12 months)
- Time to First VVC Episode From Study Day 17 to 360 - Participants <40 Years Old(12 months)
- Serum Anti-Als3 IgA1 Titers Over the 12-month Post-vaccination Period(0, 14, 28, 90, 180 and 360 days)
- Cervicovaginal Wash Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period(0, 14, 28, 90, 180 and 360 days)
- Number of Patients <40 Years Old Who Were Recurrence-free Over the 12-month Post-vaccination Period(12 months)
- Serum Anti-Als3 IgG Titers Over the 12-month Post-vaccination Period(0, 14, 28, 90, 180 and 360 days)