Safety Study of Monoclonal Antibodies to Reduce the Vaginal Transmission of HSV and HIV
Condition: HIV; Herpes Simplex Infections
MeSH terms: Herpes Simplex
Study type: Interventional
Phase: Phase 1

Summary: 
      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).
    

Detailed 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.
    

Intervention name(s): MB66; Placebo Film
Intervention type(s): Drug; Drug
Intervention description(s): 10 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film; The placebo film is composed of the identical excipients as MB66 without the monoclonal antibodies.
Other intervention name(s): Investigational Product; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment