Safety Study of MucoCept-CVN

Official title

Phase 1 Randomized Double-Blind Placebo-Controlled Safety Study of MucoCept-CVN (Lactobacillus Jensenii 1153-1666) Administered Vaginally to Healthy Women

Overview

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.

Detailed description

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.

Interventions

• Drug Live Biotherapeutic Product L. jensenii 1153-1666
  The vaginally administered MucoCept-CVN contains Lactobacillus jensenii 1153-1666, a natural component of the human vaginal microbiota that has been modified to continuously express the potent HIV entry inhibitor modified-cyanovirin-N (mCV-N) right at the site of infection. MucoCept-CVN is supplied as a prefilled vaginal applicator containing Lactobacillus jensenii 1153-1666, a modified strain of L. jensenii 1153 by integrating a modified cyanovirin-N gene into its chromosome to enhance the str
• Drug Placebo
  Each placebo applicator contains 200 mg of placebo powder comprising the same inactive ingredients of the preservation matrix as the study product.

Primary outcome measures

• Safety of MucoCept-CVN - Adverse Events [Time frame: From enrollment to the end of follow up at 8 weeks]
• Antibiotic Clearance of L.jensenii 1153-1666 [Time frame: From enrollment to the end of follow up at 8 weeks]

Secondary outcome measures (4)

• Safety of MucoCept-CVN - Vaginal Inflammation [Time frame: From enrollment to the end of follow up at 8 weeks]
• Vaginal Colonization with L. jensenii 1153-1666 [Time frame: From enrollment to the end of follow up at 8 weeks]
• Tolerability - Proportion of participants not stopping the study due to Adverse Events [Time frame: From enrollment to the end of follow up at 8 weeks]
• Acceptability [Time frame: From enrollment to the end of follow up at 8 weeks]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 1 center

• UCSF Zuckerberg San Francisco General Hospital — San Francisco

Identifiers

NCT: NCT07181486 · U01AI186333 · U01AI186333

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗