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About
The purpose of this study is to assess the safety and pharmacokinetics of MB66, a monoclonal antibody film for vaginal application that is being developed to potentially reduce the transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV).
Full description
This is a single center, Phase 1, randomized, single blind, placebo-controlled, two-segment study to assess the safety of the MB66 vaginal film. After appropriate screening, approximately 43 healthy women will be enrolled. The study will be divided into two sequential Segments. The first, Segment A, is a single-arm, single-dose, open label design. The 8 Segment A participants will receive a single dose of one full MB66 film. After dosing, subjects will be asked to maintain sexual abstinence and will be evaluated in person on Day 1 (24-hours post MB66 administration), by telephone on Day 3 or 4 and in person on the Day 6-10 Exit Visit, after which subjects will be allowed to resume sexual activity with study-provided condoms until three weeks after last exposure to film (to avoid male exposure to residual drug product). A placebo arm is not included in Segment A, because the very low risk of toxicity of the placebo film makes it unlikely that any toxicity observed in Segment A would be wrongly attributed to the active agents (mAbs) in the MB66 film. This conclusion is based on the known tolerance of the very similar vehicle used in a commercial polyvinyl alcohol (PVA)-based vaginal film (VCF®), and the absence of toxicity of the MB66 placebo film in the very sensitive rabbit model after substantially higher dosing intensity and duration.
Completion of Segment A and a safety review of Segment A adverse events will trigger the initiation of Segment B, a repeat dose, randomized, two arm, single-blind, placebo-controlled design. Subjects will be randomized 1:1 into two groups (15 evaluable subjects per group) and be treated once daily with either 1 MB66 film or 1 vehicle control placebo film for seven consecutive days. For five days before, and for 7 days after the dosing period, subjects will be asked to maintain a period of sexual abstinence. Subjects will be evaluated in person on Day 0 (at 1 and 4 hours post MB66 in-clinic dosing), again on Day 1 (24 hr post dosing), by telephone on Day 3-4, and evaluated again in person on Day 7-8, after which, subjects will be allowed to resumed sexual activity with condoms required until three weeks after last film insertion. Subjects will be evaluated a last time on the Day 12-16 Exit Visit.
In addition to safety measures, pharmacokinetic evaluations will be done on Day 0, Day 1, and Day 7 in both Segments, and additionally on Day 14 for Segment B. Specifically, this study will evaluate the rate of MB66 film dissolution, the vaginal concentrations of the MB66 antibodies, and the degree of systemic absorption of the MB66 antibodies. A number of of exploratory objectives will also be evaluated, including assessment of the antiviral effect of the MB66 antibodies ex vivo in cervicovaginal lavage fluid from participants after dosing with MB66 film, the effects of MB66 and placebo films on the cervicovaginal microbial environment using pH, Nugent score, and bacterial ribosomal DNA polymerase chain reaction (PCR), and comparison of the effect of MB66 and placebo films on cervicovaginal immune mediators by Luminex and ELISA assays. Segment B participants will also be asked to assess the acceptability of the MB66 vaginal film after 7 days of use.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Menopausal at screening (as defined as amenorrhea or irregular periods for one year or more without an alternative etiology)
Hysterectomy
Known adverse reaction to any of the study products (ever)
Known adverse reaction to latex (ever)
Non-therapeutic injection drug use in the 12 months prior to screening
Surgical procedure involving the pelvis in the 90 days prior to screening (includes dilation and curettage or evacuation, and cryosurgery; does not include cervical biopsy for evaluation of an abnormal pap smear or IUD placement)
Participation in a drug, spermicide and/or microbicide study in the 30 days prior to screening or anticipated participation in an investigational drug study in the next 8 weeks
Pregnancy within 90 days prior to screening
Lactating
Use of a diaphragm, NuvaRing®, or spermicide for contraception
As determined by the PI, a degree of menstrual cycle irregularity that would make it difficult to schedule follow up visits without interruption by menses
Active sexually transmitted infection or documented treatment of sexually transmitted infections in the last 6 months, including, but not limited to: chlamydia, gonorrhea, syphilis, trichomonas, cervicitis or pelvic inflammatory disease, or currently active HSV lesions or other sores. (Participants seropositive for or with a history of HSV without current active lesions will not be excluded.)
Women who by history engage in condom-less intercourse with HIV-infected partners, or who exchange sex for money, shelter, or gifts, or who in the opinion of the investigators, may be at risk for HIV acquisition during the duration of the study
More than one sex partner within the past 3 months
Current sexual partner known by participant to be HIV seropositive
Current or planned use of pre-exposure prophylaxis against HIV infection
Currently active genital HSV lesions, or other genital tract epithelial disruption or inflammation
Current or episodic use of anti-herpes suppressive therapy
Urinary tract infection, symptomatic candidiasis, or symptomatic bacterial vaginosis within 14 days of enrollment, or currently residual symptoms thereof Note: women with these infections at screening can be enrolled after treatment and resolution of the infection.
Antibiotic or antifungal therapy (vaginal or systemic) within 7 days of enrollment
Use of systemic immunomodulatory medications within 4 weeks of enrollment
Menses or other vaginal bleeding at the time of enrollment* or expecting menses in the 10 days after enrollment (Segment A participants) or 16 days after enrollment (for Segment B participants)
*Note: for women with monthly cycles, every attempt will be made to enroll these participants in the first half of their menstrual cycle. Women who have vaginal bleeding at the scheduled Enrollment Visit may return at a different date to be re-examined and possibly enrolled provided they are still within the screening window and meet all criteria.
Lack of stable living conditions to allow reliable room temperature storage of study product (Segment B participants only)
At enrollment has any of the following laboratory abnormalities per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, Nov 2014:
As determined by the Principal Investigator (PI), any subject who has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease, anticoagulation with warfarin or heparin; or any other condition that, in the opinion of the Investigator, would preclude provision of consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Primary purpose
Allocation
Interventional model
Masking
38 participants in 3 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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