Phase 1 Randomized Double-Blind Placebo-Controlled Safety Study of MucoCept-CVN (Lactobacillus Jensenii 1153-1666) Administered Vaginally to Healthy Women
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Safety of MucoCept-CVN - Adverse Events
研究概览
简要总结
MucoCept-CVN uses a Lactobacillus strain native to the human vagina that is modified into a live biotherapeutic product (LBP) that continuously expresses a potent anti-HIV drug. If research shows that MucoCept-CVN is safe and effective, it could become a self-renewing, female-initiated prevention product for women that promotes vaginal health and provides protection from HIV.
The goal of this first-in-human Phase 1 dose-ranging, randomized, placebo-controlled study of MucoCept-CVN is to collect data on safety, colonization, changes to the vaginal microbiota and clearance of the strain with antibiotics.
Twelve healthy women will be enrolled and take either one or three doses of MucoCept-CVN or placebo, and a week later will receive antibiotics to clear the Lactobacillus strain.
If research shows that MucoCept-CVN is safe and effective, it could become a self-renewing, long-acting, female-initiated prevention product for women that promotes vaginal health and provides protection from HIV.
详细描述
The goal of this first-in-human Phase 1 dose-ranging, randomized, placebo-controlled study is to collect critical data needed to advance the clinical development of MucoCept-CVN, specifically (1) understanding factors that influence vaginal colonization by L. jensenii 1153-1666, including dose and endogenous vaginal microbiota; and (2) pharmacokinetic, tissue and systemic effects of L. jensenii 1153-1666, such as adverse events (AE) and findings in colposcopy and vaginal biopsy, and (3) changes to the vaginal microbiota. We also need to show that (4) L. jensenii 1153-1666 can be sufficiently cleared with antibiotics should the need arise for rescue therapy.
Twelve healthy women will be enrolled. Two women in Cohort 1 will receive one dose of active investigational product. Four women in Cohort 2 will be randomized 1:1 to either receive one dose of active investigational product or placebo. Two women in Cohort 3 will receive three doses of active investigational product. Four women in Cohort 4 will be randomized 1:1 to either receive three doses of active investigational product or placebo. Participants will be closely followed over the course of 23-37 days until antibiotic clearance of L. jensenii 1153-1666 is achieved, with a final follow-up visit occurring 30 days after clearance (Day 53-67).
Any sexual partners of study participants will be informed and consented before enrollment of study participants, and need to agree to sexual abstinence during the study. Should exposure to L. jensenii 1153-1666 occur in sexual partners, they will receive testing for L. jensenii 1153-1666 and antibiotic clearance as safety management.
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)
盲法说明
For this first-in-human study, the first two participants for single dose (Cohort 1) and triple dose (Cohort 3) are unblinded and will receive the investigational product MucoCept-CVN.
Cohort 2 (single dose randomized) and Cohort 4 (triple dose randomized) are double-blinded.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy pre-menopausal women 18-45 years of age, inclusive, with regular predictable menstrual cycles
- •Ability to read and consent in English
- •Previous experience of gynecological examinations
- •Consent to participate and adhere to all procedures, including frequent visits at the UCSF Clinical Research Center (CRC) facility for at least 53 days
- •Agree to get tested for STIs and a Pap Smear
- •Agree not to use any other vaginal product during the course of the study, including spermicides
- •Agree to sexual abstinence (no vaginal, anal, and receptive oral intercourse) until the elimination of L. jensenii 1153-1666 is confirmed and for 12 hours prior to the final study visit after clearance is confirmed
- •For participants with male sexual partners: Agree to use two forms of contraception, condoms plus hormonal or permanent method (intrauterine device [IUD] or tubal ligation) during vaginal intercourse from the time clearance is established to the Final Visit 30 days after clearance. Use of spermicides is not permitted.
- •For participants with female sexual partners: Agree to use female condoms during intercourse from the time clearance is established to the Final Visit 30 days after clearance. Use of hormonal or permanent method of contraception (IUD or tubal ligation) is not required.
- •Agree to inform their sexual partner about the goals of the study and importance of sexual abstinence (no vaginal, anal, and receptive oral intercourse) and present with their partner at enrollment visit for separate consent procedure for partners
- •Current sexual partners of participants must meet all the following criteria to be enrolled:
- •Ability to read and consent in English
- •Consent to participate and adhere to all procedures for sexual partners should exposure to L. jensenii 1153-1666 be suspected, including multiple visits at the UCSF Clinical Research Center (CRC)
- •Agree to sexual abstinence (no vaginal, anal, and receptive oral intercourse) until the elimination of L. jensenii 1153-1666 is confirmed, and for 12 hours prior to the final study visit after clearance is confirmed
排除标准
- •Urogenital infection, including UTI, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, HIV-1/2, BV, or vulvovaginal candidiasis
- •Abnormal Pap smear result
- •Pregnancy or within two months of last pregnancy or lactation
- •Antibiotic or antifungal therapy (vaginal or systemic) within 30 days of enrollment
- •Investigational or immune-suppressive drug use within 30 days of enrollment visit or 10 half-lives, or planned during the study
- •Intrauterine device insertion or removal, pelvic surgery, cervical cryotherapy, cervical laser or loop electrosurgical procedure, abortion, labioplasty within three months prior to enrollment
- •Findings during the pelvic exam at the enrollment visit involving significant deep disruption of the epithelium (e.g., Herpes genitalis lesions)
- •Known allergy to any component used in MucoCept-CVN or clindamycin and azithromycin in participant or sexual partner(s), including azithromycin-associated cholestatic jaundice.
- •History of transplant surgery, cancer, HIV, diabetes or condition that could facilitate the growth of microorganisms
- •Recent history of drug or alcohol abuse
- •Unwillingness to abstain from sexual activity during study by participant or sexual partner(s)
- •If in a sexual relationship, inability to present with their sexual partner before enrollment
- •If in a sexual relationship, having multiple concurrent partners or anonymous partners.
- •Any other condition which the study clinician feels would limit the participant's ability to be an appropriate study subject
- •History of regional enteritis (Crohn's disease), ulcerative colitis, or "antibiotic-associated" colitis
- •For sexual partners of study participants, the following exclusion criteria apply:
- •Known allergy to any component used in MucoCept-CVN or clindamycin and azithromycin, including azithromycin-associated cholestatic jaundice.
- •Having multiple concurrent sex partners or anonymous sex partners.
- •HIV-1/2 infection
- •Any other condition which the study clinician feels would limit the ability of sexual partner(s) to complete the study
- •Co-enrollment in clinical trials testing study drugs
研究组 & 干预措施
Single Dose MucoCept-CVN
Two women in Cohort 1 will receive a single dose of active investigational product. Two of four women in Cohort 2 (1:1 randomization) will receive a single doses of active investigational product.
干预措施: Live Biotherapeutic Product L. jensenii 1153-1666 (Drug)
Placebo (Single Dose and Triple Dose)
Two of four women in Cohort 2 (1:1 randomization) will receive one dose of placebo.
Two of four women in Cohort 4 (1:1 randomization) will receive three dose of placebo.
干预措施: Placebo (Drug)
Triple Dose MucoCept-CVN
Two women in Cohort 3 will receive three doses of active investigational product. Two of four women in Cohort 4 (1:1 randomization) will receive three doses of active investigational product.
干预措施: Live Biotherapeutic Product L. jensenii 1153-1666 (Drug)
结局指标
主要结局
Safety of MucoCept-CVN - Adverse Events
时间窗: From enrollment to the end of follow up at 8 weeks
Proportion of participants with serious adverse events, any genital AEs and Grade 2 or above systemic AEs.
Antibiotic Clearance of L.jensenii 1153-1666
时间窗: From enrollment to the end of follow up at 8 weeks
Inability to clear L. jensenii 1153-1666 after administration of antibiotics, using next generation sequencing (NGS).
次要结局
- Safety of MucoCept-CVN - Vaginal Inflammation(From enrollment to the end of follow up at 8 weeks)
- Vaginal Colonization with L. jensenii 1153-1666(From enrollment to the end of follow up at 8 weeks)
- Tolerability - Proportion of participants not stopping the study due to Adverse Events(From enrollment to the end of follow up at 8 weeks)
- Acceptability(From enrollment to the end of follow up at 8 weeks)
研究者
Craig Cohen, MD, MPH
Professor, Obstetrics, Gynecology, and Reproductive Sciences
University of California, San Francisco