Safety Study of Monoclonal Antibodies to Reduce the Vaginal Transmission of HSV and HIV

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.