Phase II-b Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus Crispatus CTV-05 (LACTIN-V) to Prevent the Recurrence of Bacterial Vaginosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 228
- 试验地点
- 4
- 主要终点
- The Proportion of Participants Reporting Product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) in Each Study Arm.
研究概览
简要总结
This Phase 2b trial is designed to provide a screening evaluation for the hypothesis that, following a 5-day treatment with MetroGel® to treat BV, L. crispatus CTV-05 (LACTIN-V, Osel, Inc.) administered at 2 x 10^9 cfu/dose using a vaginal applicator reduces the 12-week incidence of BV recurrence when compared to placebo. The primary objectives of this study are: 1) To estimate the efficacy of repeated doses of LACTIN-V (2 x 10^9 cfu/dose) as compared to placebo in preventing BV recurrence by 12 weeks following treatment of BV with MetroGel vaginal gel (MetroGel). 2) To assess the safety of LACTIN-V over 24 weeks by comparing the incidence of AEs between individuals randomized to LACTIN-V or placebo.
详细描述
This is a Phase II-b multicenter randomized double-blind placebo-controlled trial to assess the efficacy of repeated doses of LACTIN-V compared to placebo in preventing BV recurrence in women diagnosed with BV. The study will also assess the safety of LACTIN-V by comparing the incidence of AEs between women randomized to LACTIN-V or placebo. The study plans to enroll 228 non-pregnant, pre-menopausal women age 18 to 45 years. Women will be randomized 2:1 to receive LACTIN-V or placebo. Potentially eligible women will start a standard 5-day course of MetroGel. Women will return to the study clinic within 2 days after completing the 5-day course of MetroGel to re-evaluate eligibility criteria and review the BV test results from the screening visit. Women with Amsel criteria > /=3 and Nugent score 4-10 will be instructed to administer the LACTIN-V or placebo at home for 5 consecutive days and then twice weekly for 10 weeks. The primary objectives of this study are: 1) To estimate the efficacy of repeated doses of LACTIN-V (2 x109 cfu/dose) as compared to placebo in preventing BV recurrence by 12 weeks following treatment of BV with MetroGel vaginal gel (MetroGel). 2) To assess the safety of LACTIN-V over 24 weeks by comparing the incidence of AEs between individuals randomized to LACTIN-V or placebo. Secondary objectives are: 1) To investigate the colonization of LACTIN-V (presence of L. crispatus CTV-05 in the vaginal specimen) and fluctuations over 12 weeks, in relation to menses and sexual intercourse 2) To evaluate user acceptability and tolerability of LACTIN-V over 12 weeks, including perceptions around method of delivery and dosing. 3) To measure long-term colonization of LACTIN-V at 24 weeks (12 weeks after last dosing) 4) To estimate the long-term efficacy of repeated doses of LACTIN-V (2 x 109 cfu/dose) as compared to placebo in preventing BV recurrence at 24 weeks (12 weeks after last dosing)
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Capable of reading and writing English and voluntarily provide written informed consent to participate in the study and comply with all study procedures
- •Untreated BV (asymptomatic or symptomatic) as diagnosed during the screening visit defined by >/=3 Amsel criteria. Note: Amsel criteria include the following: --Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls; --Vaginal pH >4.5; --Positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10% potassium hydroxide (KOH) is added to a sample of vaginal discharge; --Presence of clue cells (>20% on microscopy).
- •Untreated BV(asymptomatic or symptomatic) as confirmed in the laboratory using the Nugent scoring system (Nugent Score >/= 4)
- •Otherwise healthy pre-menopausal women 18-45 years of age on the day of screening
- •Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of a long-acting progestin or continuous use of oral contraceptives
- •Willing to be asked questions about personal medical health and sexual history.
- •Willing to apply study agent vaginally and comply with study examinations.
- •Agree to abstain from sexual intercourse during the first 5 consecutive days of study product administration, 12 hours prior to study visits and for 12 hours after each study product application
- •Agree to abstain from the use of any other intravaginal product throughout the trial period from the time of screening through Visit 7 (Week 24, Day 168) Note: Intravaginal products include contraceptive creams such as Gynol II, gels, foams, sponges, lubricants not approved by the study investigators, and douches. Limit use of tampons during menstruation to unscented products.
- •Must be of non-childbearing potential or if of childbearing potential, must agree to use a reliable method of birth control for the duration of the study Note: Reliable methods of birth control include tubal ligation, male partner with a vasectomy, a steroidal contraceptive (oral, patch, injectable or implantable), IUD, condoms or abstinence.
排除标准
- •Urogenital infection at screening Note: Urogenital infection includes urinary tract infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Treponema (T.) pallidum, or vulvo-vaginal candidiasis.
- •Diagnosis of two or more outbreaks of N. gonorrhoeae, C. trachomatis, T. pallidum, T. vaginalis, or herpes simplex virus (herpes genitalis) within 6 months prior to screening
- •Positive for syphilis or HIV at screening
- •Current pregnancy or within 2 months of last pregnancy and/or currently breastfeeding**. Criteria will be assessed at screening and enrollment.
- •Vaginal or systemic antibiotic or antifungal therapy (other than MetroGel given as part of study procedures) within 21 days of screening or within 30 days of enrollment**
- •Use of disulfiram within past 2 weeks or other contraindication to use of MetroGel**
- •Any condition requiring regular periodic use of systemic antibiotics during participation in the trial
- •Active genital herpes lesion** (if not resolved by enrollment)**
- •Investigational drug use other than LACTIN-V within 30 days or 10 half-lives of the drug, whichever is longer, of enrollment visit**
- •Other planned participation in an investigational drug study while participating in this study**
- •Menopause defined as more than 12 consecutive months of amenorrhea without another known cause including pregnancy
- •IUD insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser treatment within the last 2 months prior to screening
- •Use of vaginal ring (eg, NuvaRing) within 3 days of screening or during the course of the study**
- •Failure to complete 5 days of MetroGel with the last dose taken no later than 48 hours prior to randomization***
- •Use of new long-acting hormonal treatments. Participant may be enrolled if stable (>3 months) on existing therapy as determined by the principal investigator**
- •Known allergy to any component of LACTIN-V/placebo or MetroGel or to nitroimidazole derivatives or latex (condoms)
- •Any social, medical, or psychiatric condition, including history of drug or alcohol abuse that in the opinion of the investigator would make it unlikely for the participant to comply with the study ** Note: Criteria will be assessed at screening and enrollment. ***Note: Criteria will be assessed at enrollment
研究组 & 干预措施
LACTIN-V
Subjects receive 5-day course of metronidazole gel 7.5 mg/gm daily applied vaginally. Subjects then receive LACTIN-V 2x10^9 cfu/dose applied vaginally for 5 days then twice weekly for 10 weeks. N=152
干预措施: Lactobacillus crispatus CTV-05 (Biological)
LACTIN-V
Subjects receive 5-day course of metronidazole gel 7.5 mg/gm daily applied vaginally. Subjects then receive LACTIN-V 2x10^9 cfu/dose applied vaginally for 5 days then twice weekly for 10 weeks. N=152
干预措施: Metronidazole (Drug)
Placebo
Subjects receive 5-day course of metronidazole gel 7.5 mg/gm daily applied vaginally. Subjects then receive placebo applied vaginally for 5 days then twice weekly for 10 weeks. N=76
干预措施: Metronidazole (Drug)
Placebo
Subjects receive 5-day course of metronidazole gel 7.5 mg/gm daily applied vaginally. Subjects then receive placebo applied vaginally for 5 days then twice weekly for 10 weeks. N=76
干预措施: Placebo (Other)
结局指标
主要结局
The Proportion of Participants Reporting Product-related Adverse Events (AEs) and Serious Adverse Events (SAEs) in Each Study Arm.
时间窗: Day 1 to Day 168
Adverse events and serious adverse events were collected during the entire study period. Relatedness to study product was assessed by the site investigator according to the protocol definition of related as "There is a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE."
The Proportion of Participants With a Positive BV Diagnosis in Each Study Arm.
时间窗: Day 1 to Day 84
A positive BV diagnosis was defined by meeting at least 3 of the 4 Amsel criteria and a Nugent score of 4-10. Amsel criteria are: homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls; vaginal pH \>4.5; positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10% potassium hydroxide is added to a sample of vaginal discharge; and presence of clue cells (\>20%) on microscopy. The Amsel score ranges from 0-4, where higher scores mean a worse outcome. The Nugent score is calculated by assessing for the presence of large Gram-positive rods scored as 0 to 4, small Gram-variable rods scored as 0 to 4, and curved Gram-variable rods scored as 0 to 2, and adding all component scores. The Nugent score ranges from 0-10, where higher scores mean a worse outcome. All BV diagnoses following 15 days after enrollment (22 days after commencement of MetroGel treatment) were considered a recurrent episode.
次要结局
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction as Influence(Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Continuous/Discrete Response Regarding Product(Day 84)
- The Number of Participants Who Discontinued Study Product Early in Each Study Arm Due to Adverse Events.(Day 1 to Day 84)
- The Proportion of Participants Who Are Compliant With the Complete Dose Regimen as Assessed by Participant Reporting and Applicator Staining.(Day 1 to Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Categorical Variables on Likert Scale(Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Likelihood to Use(Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Current Partner's Reaction to the Product(Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Experience Side Effects(Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Experience of Side Effects Make Less Likely to Use(Day 84)
- Acceptability of LACTIN-V and the Applicator Measured by Self-administered Questionnaires About Acceptability - Continuous/Discrete Response Regarding Product Use(Day 84)
- The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product in the LACTIN-V Arm Overall.(Day 1 to Day 84)
- The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Intercourse.(Day 84)
- The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product by Occurrence of Menses.(Day 84)
- The Proportion of Participants Experiencing Successful Colonization With L. Crispatus CTV-05 Following Dose of Study Product Overall.(Day 1 to Day 168)
- The Proportion of Participants With a Positive BV Diagnosis in Each Study Arm.(Day 1 to Day 168)