HIV -1 Infection
Conditions
Keywords
HIV prevention, live biotherapeutic product, MucoCept-CVN, Vaginal microbiome
Brief summary
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
DRUGLive 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 strain's ability to inhibit HIV. Each applicator contains 200 mg of MucoCept-CVN powder (1 x 109 CFU), and an inactive preservation matrix.
DRUGPlacebo
Each placebo applicator contains 200 mg of placebo powder comprising the same inactive ingredients of the preservation matrix as the study product.
Sponsors
Craig Cohen, MD, MPH
Osel, Inc.
Duke University
DFNet Research Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy pre-menopausal women 18-45 years of age, inclusive, with regular predictable menstrual cycles 2. Ability to read and consent in English 3. Previous experience of gynecological examinations 4. Consent to participate and adhere to all procedures, including frequent visits at the UCSF Clinical Research Center (CRC) facility for at least 53 days 5. Agree to get tested for STIs and a Pap Smear 6. Agree not to use any other vaginal product during the course of the study, including spermicides 7. 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 8. 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. 9. 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. 10. 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: 1. Ability to read and consent in English 2. 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) 3. 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
1. Urogenital infection, including UTI, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, HIV-1/2, BV, or vulvovaginal candidiasis 2. Abnormal Pap smear result 3. Pregnancy or within two months of last pregnancy or lactation 4. Antibiotic or antifungal therapy (vaginal or systemic) within 30 days of enrollment 5. Investigational or immune-suppressive drug use within 30 days of enrollment visit or 10 half-lives, or planned during the study 6. Intrauterine device insertion or removal, pelvic surgery, cervical cryotherapy, cervical laser or loop electrosurgical procedure, abortion, labioplasty within three months prior to enrollment 7. Findings during the pelvic exam at the enrollment visit involving significant deep disruption of the epithelium (e.g., Herpes genitalis lesions) 8. Known allergy to any component used in MucoCept-CVN or clindamycin and azithromycin in participant or sexual partner(s), including azithromycin-associated cholestatic jaundice. 9. History of transplant surgery, cancer, HIV, diabetes or condition that could facilitate the growth of microorganisms 10. Recent history of drug or alcohol abuse 11. Unwillingness to abstain from sexual activity during study by participant or sexual partner(s) 12. If in a sexual relationship, inability to present with their sexual partner before enrollment 13. If in a sexual relationship, having multiple concurrent partners or anonymous partners. 14. Any other condition which the study clinician feels would limit the participant's ability to be an appropriate study subject 15. History of regional enteritis (Crohn's disease), ulcerative colitis, or "antibiotic-associated" colitis For sexual partners of study participants, the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of MucoCept-CVN - Adverse Events | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of MucoCept-CVN - Vaginal Inflammation | From enrollment to the end of follow up at 8 weeks | Proportion of participants with colposcopic findings and inflammation in vaginal biopsy. |
| Vaginal Colonization with L. jensenii 1153-1666 | From enrollment to the end of follow up at 8 weeks | Proportion of participants with achieved vaginal colonization and clearance of vaginal colonization with L. jensenii 1153-1666, using next generation sequencing (NGS). |
| Tolerability - Proportion of participants not stopping the study due to Adverse Events | From enrollment to the end of follow up at 8 weeks | Tolerability as proportion of participants not stopping the study due to AE. |
| Acceptability | From enrollment to the end of follow up at 8 weeks | Acceptability of MucoCept-CVN using a self-administered questionnaire at enrollment and final visit, including perceptions around method of delivery and dosing, and self-reported attitudes about positive and negative study product attributes. |
Countries
United States
Contacts
CONTACTAnke Hemmerling, MD, PhD, MPH
CONTACTCraig R Cohen, MD, MPH
PRINCIPAL_INVESTIGATORCraig Cohen, MD, MPH
University of California, San Francisco
Outcome results
None listed