Microbicide Trials Network

MTN-038

Details

Protocol Title: 
A Phase 1, Randomized, Pharmacokinetic and Safety Study of a 90 Day Intravaginal Ring Containing Tenofovir
DAIDS Protocol ID: 
38460
Status: 
In Development

Protocol Chair(s)

Albert Liu (Protocol Chair)

Description

Multiple clinical trials have evaluated the safety and effectiveness of TFV for the prevention of HIV acquisition in vaginal gel and in oral tablet formulations.  These clinical trials support the favorable safety profile and tolerability of TFV in general and specifically in vaginal and oral delivery formulations. The development of an extended duration intravaginal ring (IVR) may allow less frequent IVR replacements (e.g., quarterly basis instead of monthly basis) that may further reduce patient and provider burden, streamline follow-up, and improve adherence. Such a delivery mechanism could overcome the adherence and efficacy issues observed with the vaginal gel formulation of TFV and challenges with daily dosing of oral TDF/FTC, thus providing a viable vaginal delivery complement to the oral tablet.

 

MTN-038 is a Phase 1, two-arm, multi-site, randomized (2:1), placebo-controlled trial. The study will evaluate the safety and PK of a 90-day TFV IVR. The study population will consist of healthy, HIV-uninfected women ages 18-45. Participants will be randomized (2:1) to TFV IVR or placebo, and will use the assigned IVR for approximately 90 days. It is anticipated that this study will take approximately 6-9 months to enroll the target sample size, and that total study duration for participants will be approximately 13 weeks. MTN-038 will evaluate TFV and TFV-DP levels in plasma, cervicovaginal fluid (CVF), rectal fluid, and cervical tissue during approximately 91 days of continuous use of a single ring containing 1.4 g TFV. PK data will help determine the concentration-time profile using pooled data across all participants. The study design includes frequent collection of corresponding blood, rectal and CVF samples following the insertion of a TFV IVR to allow for the detection of drug release from the ring.  PK parameters of TFV will be calculated for blood plasma, CVF, rectal fluid, and cervical tissue. It is hypothesized that plasma, CVF, and rectal fluid TFV levels and cervical tissue TFV and TFV-DP levels will be measurable in all participants, and that continuous exposure to TFV due to sustained release from the 1.4 g TFV IVR for 91 days will be safe.