MTN-028

Primary Objective

• Assess local pharmacokinetics (PK) of vicriviroc (MK-4176) and MK-2048 during and after 28-days of continuous use of two MK-2048A IVRs containing different dose strengths

Study Summary
MTN-028 was a single-site, single-blind, two-arm, randomized Phase 1 safety and PK trial of two IVRs containing a combination of a CCR5-receptor antagonist, VCV (MK-4176), with an integrase inhibitor, MK-2048. The two rings tested in MTN-028 were formulated with different dose strengths. The study enrolled 18 evaluable healthy, 18-45-year-old HIV-uninfected, non-pregnant, sexually abstinent women who were using adequate contraception. Women were randomized to one of two study regimens in a 2:1 ratio (low dose: original dose). The IVR was used continuously for approximately 28 consecutive days. Two different formulations of the MK-2048A combination IVR were developed and evaluated in MTN-028 to inform in vitro and in vivo modeling to further optimize the drug release profiles of an IVR containing VCV and MK-2048 for use in future studies, including the potential development of a combination antiretroviral/contraceptive ring. MTN-027 and MTN-028 were the first clinical trials to test an integrase inhibitor as a microbicide.

MTN-028 completed follow-up on March 22, 2016. The primary manuscript, the only paper from this study, was published in Clinical Infectious Diseases in March 2019.

Primary Results
The two doses/formulations of a combination VCV/MK-2048 IVR were safe and well-tolerated. All AEs reported were grade 1 or 2, with no statistically significant differences in related genitourinary AEs or grade ≥2 AEs observed between arms (P = >.99). VCV/MK-2048 concentrations rose rapidly, with higher plasma area under the concentration-time curve (AUC) in the original-dose arm (geometric mean ratio, 3.29 for VCV and 1.49 for MK-2048) and similar AUCs across arms for CVF samples. Cervical tissue concentrations were higher in the original-dose arm (geometric mean ratio, 7.94 for VCV and 6.45 for MK-2048), with greater drug released based on residual drug levels. Plasma and CVF concentrations for both drugs fell rapidly after ring removal.