MTN-028 is 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:
- Formulation A (Low dose): IVR containing 91 mg of VCV (MK-4176) and 10 mg of MK-2048
- Formulation B (Original dose): IVR containing 182 mg VCV (MK-4176) 30 mg MK-2048
The study enrolled 18 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. The IVR was worn 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 were evaluated in MTN-028 in an effort 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. Safety data from MTN-027 will be considered in the analysis of MTN-028.
MTN-027 and MTN-028 are the first clinical trials to test an integrase inhibitor as a microbicide.
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