User-based identification of preferred design features for MM008, a non-hormonal contraceptive vaginal ring

基于用户的非激素避孕药MM008首选设计特征的识别 阴道环 项目摘要 在美国，近一半的怀孕是意外的，大多数发生在没有使用 避孕药。不使用避孕药的原因多种多样；一个共同的原因是 由于实际和感知的副作用，女性对使用外源性激素有强烈的反感。很有可能 如果有一个非荷尔蒙的使用者，避孕用法和满意度将大大增加- 受控避孕方法，不需要在性交前立即使用，也不要求每天服用。我们 相信我们可以创造出这样一种非荷尔蒙避孕药，这种避孕药是基于阴道交付的抗精子 一种单抗，能在粘液中凝集和捕获精子，从而防止精子 够到蛋了。我们已经开发出一种非常有效的单抗MM008，它针对的是一种具有良好特性的 所有人类精子上普遍存在的有效抗原靶标。MM008高度同质化， 稳定性好，可以使用传统的生物制造工艺以非常高的产量生产。更多 重要的是，MM008的效力是文献中已知的最好的抗精子抗体Aggulutate的16倍。 精子含量最低可达100毫微克/毫升，可使绵羊阴道内的活动性精子逐渐减少99.9% 在2分钟内，每只羊只需33微克的剂量。自那以后，我们已经证明，我们可以稳步发布MM008 来自一种专有的胶囊-阴道内环(IVR)系统，该系统可维持高效浓度的 MM008在绵羊阴道中超过20天(足以覆盖大多数受精窗口 女性)。这些非常有希望的结果促使我们积极推动MM008-IVR进入临床。我们的目标 就是开发一种既能满足许多女性的避孕需求，又能达到高效、高效的产品。 用户采用率。因此，对我们来说，严格调查用户的看法和偏好是很重要的 可能会影响他们尝试或使用该产品的意愿。在这项提案中，我们寻求回应RFA HD-22- 019以确定首选使用特征(PUC)并调查用户的感官感知和 MM008-IVR的几点体会在具体目标1中，我们将进行混合方法集成设计研究 检查非荷尔蒙避孕的可知性和PUC，包括操作上的比较 我们的MM008-IVR变种的评估。这些用户洞察力将首先通过量化调查进行 在线调查，然后是面对面的焦点小组。在具体目标2中，我们将进行短期 一项用户体验研究，以评估阴道置入和使用一种药物后的知觉和相关的PUC 非药物IVR在外观和物理特性上与AIM 1的首选MM008-IVR相同。 成功完成拟议的工作将有助于确保我们正在推进的产品能够满足 美国和世界各地数百万女性的避孕需求和偏好。

User-based identification of preferred design features for MM008, a non-hormonal contraceptive vaginal ring Project Summary Nearly half of all pregnancies in the U.S. are unintended, and most occur in women who are not using contraceptives. There are diverse reasons for not using contraceptives; one common reason is that many women have a strong aversion to using exogenous hormones due to real and perceived side effects. It is likely that contraceptive use and satisfaction would substantially increase if there was a non-hormonal, user- controlled contraceptive method that did not require use immediately prior to intercourse, nor daily dosing. We believe we can create such a non-hormonal contraceptive based on vaginal delivery of an anti-sperm monoclonal antibody (mAb) that agglutinates and traps sperm in mucus, thereby preventing sperm from reaching the egg. We have developed an exceptionally potent mAb, MM008, that target a well characterized and validated antigen target universally present on all human sperm. MM008 is highly homogeneous and stable, and can be produced at very high yields using conventional biomanufacturing processes. More importantly, MM008 is >16-fold more potent than the best anti-sperm IgG known in the literature, aggulutinate sperm even down to <100 ng/mL, and can reduce progressively motile sperm by 99.9% in the sheep vagina within 2 mins at a dose of just 33 µg per sheep. We have since shown that we can steadily release MM008 from a proprietary capsule-intravaginal ring (IVR) system that sustains highly effective concentrations of MM008 in the sheep vagina for over 20 days (more than adequate to cover the fertility window in most women). These highly promising results motivated us to actively advance MM008-IVR into the clinic. Our goal is to advance a product that suits the contraceptive needs for many women, with both high efficacy and high user adoption. Thus, it is important for us to rigorously investigate user pereceptions and preferences that could impact their willingness to try or use the product. In this proposal, we seek to respond to the RFA HD-22- 019 to identify preferred use characteristics (PUC) and investigate the user sensory perceptions and experiences for MM008-IVR. In Specific Aim 1, we will conduct mixed method integrative design study to examine the perceptibility and PUCs of non-hormonal contraception, including an in mano comparative assessment of variants of our MM008-IVR. These user insights will be investigated initially through quantitative online survey, and then followed by in-person focus groups. In Specific Aim 2, we will conduct a short-term user experience study to evaluate the perceptibility and related PUC following vaginal insertion and use of a non-medicated IVR identical in appearance and physical properties to the preferred MM008-IVR from Aim 1. Successful completion of the proposed work will help ensure we are advancing a product that can meet the contraceptive needs and preferences of millions of women in the U.S. and worldwide.