MTN-044/IPM 053/CCN019

Primary Objective

• To characterize the local and systemic pharmacokinetics of one DPV-LNG vaginal ring formulation used either continuously or cyclically (~28/2) for approximately 90 days

Study Summary
MTN-044/IPM 053/CCN019 was a single-site, randomized (1:1), open-label Phase 1 trial. The study assessed the pharmacokinetics and safety of one silicone elastomer vaginal matrix rings containing 200 mg of dapivirine and 320 mg of levonorgestrel. The study enrolled 25 healthy, HIV-uninfected, non-pregnant women between 18-45 years of age. The participants used the vaginal ring either continuously or cyclically (worn for 28 days and taken out for two days) for approximately 90 days and were followed up for a total duration of approximately 26 weeks. The primary focus of MTN-044/IPM 053/CCN019 was the collection of pharmacokinetic and safety data on the vaginal ring containing a combination of dapivirine and levonorgestrel, formulated with higher dapivirine dose strengths than previously evaluated in Phase 3 trials. Furthermore, MTN-044/IPM 053/CCN019 assessed the vaginal bleeding patterns associated with using the DPV-LNG VR either continuously or cyclically for approximately 90 days. This study also investigated the acceptability of and adherence to this biomedical HIV prevention-plus-contraception method and evaluated the vaginal microenvironment (microflora and biomarkers) and the HIV inhibitory activity in cervical tissue during approximately 90 days of continuous or cyclic study product use. MTN-044/IPM 053/CCN019 was the first study to assess local and systemic PK, safety and tolerability of the DPV-LNG VR when used by women continuously versus cyclically for approximately 90 days.   

The study completed follow-up on October 7, 2019. Primary results were presented at the HIV Research for Prevention (HIVR4P) conference held virtually on January 27-28 and February 3-4, 2021. Primary and secondary manuscripts are in development.

Primary Results
Twenty-five evaluable participants had median age 36.0 years (range 21-43) and BMI 27 (range 20-39), and 20 (80%) self-identified as white. There were 84 AEs: 59 Grade-1, 24 Grade-2, and one Grade-4 (anemia related to cyclic product use). The number of women with =Grade-2 genitourinary AEs did not differ by continuous (3/12, 25%) or cyclic (5/13, 38%) use. With continuous use, median Cmax for DPV and LNG were 750pg/mL (IQR 475-1401) and 1675pg/mL (IQR 645-2575), respectively. Two days after ring removal (cyclic group), plasma DPV remained =concentration associated with previously demonstrated efficacy. Number of days with no bleeding, spotting/light, moderate, and heavy bleeding did not differ by use pattern. Serum DPV and LNG concentrations previously associated with efficacy for HIV and pregnancy prevention respectively are achieved or exceeded with cyclic and continuous use of this MPT ring without toxicity.