Microbicide Trials Network

MTN-028

Details

Protocol Title: 
Phase 1 Pharmacokinetic Trial of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048
DAIDS Protocol ID: 
12022
Status: 
Closed to Follow Up

Protocol Chair(s)

Albert Liu (Protocol Chair)

Description


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:

 

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 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.

Other Study Info

Sponsors:

Division of AIDS, US National Institute of Allergy and Infectious Diseases 

US Eunice Kennedy Shriver National Institute of Child Health and Human Development 

US National Institute of Mental Health 

US National Institutes of Health 

Co-Sponsors:

DAIDS 

Study Design:

Phase I, single-site, two-arm, randomized (2:1), single-blind trial