CRC OVERVIEW: ABSTRACT We propose to establish a Contraceptive Research Center (CRC) to develop a new contraception method based on the topical use of a potent antisperm monoclonal antibody (mAb). We propose to manufacture a first generation HCA contraceptive product comprised of HCA human mAb, produced to GMP standards in an innovative cost-effective mAb platform (Nicotiana), and formulated into a film that dissolves on contact with the vaginal mucosa to deliver short-term (on-demand) contraception. The HCA film will be tested in vitro for efficacy and safety, IND-enabling studies will be performed, and after filing an IND application with the FDA the HCA film will be tested for safety and efficacy in two Phase 1 clinical trials. A prototype HCA-intravaginal ring (IVR) will also be developed with the goal to provide long-term (>30 day) contraceptive protection. The HCA-IVR will undergo testing in vitro and in a nonhuman primate (NHP) model for preliminary assessment of PK/PD, antibody distribution and safety. The program will also produce and test HCA multivalent variants with potential enhanced sperm trapping capabilities for use in second generation HCA contraception products. In the future HCA could be used alone in films or IVRs for contraception, or in combination with mAbs or other microbicidal compounds directed against STI pathogens, to enhance the acceptability, efficacy and marketability of Multipurpose Prevention Technology (MPT) products.
