MTN-026

Primary Objectives

• To evaluate the safety of dapivirine gel when applied rectally.
• To characterize the systemic and compartmental pharmacokinetics of dapivirine gel following rectal application.

Study Summary
MTN-026 was a Phase 1, randomized (2:1), double-blind, multi-site, placebo-controlled trial which evaluated the safety and pharmacokinetics of dapivirine gel (0.05%) when administered rectally to healthy, HIV-1/2 uninfected men and women. MTN-026 enrolled a total of 27 evaluable participants between the ages of 18 and 45 years (inclusive). Participants were randomized to receive either a single dose of dapivirine gel (0.05%) or universal HEC placebo gel rectally, followed by seven daily doses of the same product administered under direct observation in the clinic. Specimens were collected at multiple time points to assess drug concentrations, HIV explant infection and mucosal safety. MTN-026 was the first clinical trial to collect safety and pharmacokinetic data on the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults.

MTN-026 completed follow-up on September 20, 2018. Primary results were presented at the Research for Prevention (HIVR4P) conference held virtually on January 27-28 and February 3-4, 2021. The primary manuscript was published in AIDS Research and Human Retroviruses in December 2021. A total of two papers have been published from this study.

Primary Results
Thirty adverse events occurred (all Grade 1 or 2, except one unrelated Grade 3) without study arm differences. DPV rectal tissue concentrations [median (interquartile range)] 0.5-1 and 2 h after a single dose were 256 ng/g [below the lower limit of quantification (BLQ)-666] and BLQ (BLQ-600), respectively, then BLQ (BLQ-BLQ) from 24 to 72 h; concentrations following multiple doses were similar. The largest median DPV plasma concentrations were 0.33 ng/mL (0.15-0.48) after one dose and 0.40 (0.33-0.49) after seven doses. The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.