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:
1. Formulation A (Low dose): IVR containing 91 mg of VCV (MK-4176) and 10 mg of MK-2048
2. Formulation B (Original dose): IVR containing 182 mg VCV (MK-4176) 30 mg MK-2048
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.
Based on in vitro, in vivo, and ex vivo studies, VCV (MK-4176) and MK-2048 show promise as topically- applied microbicides. The safety and acceptability of these agents alone and in combination were evaluated in the MTN-027 trial; however, the optimal dose of MK-4176 and MK-2048 to achieve sufficient vaginal fluid concentrations for antiviral activity is unknown. 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 was published in Clinical Infectious Diseases on March 19, 2019, along with the primary results manuscript for Protocol MTN-027.
US Eunice Kennedy Shriver National Institute of Child Health and Human Development
US National Institute of Mental Health
US National Institutes of Health
Phase I, single-site, two-arm, randomized (2:1), single-blind trial