MTN-037

Primary Objectives 

• To evaluate the safety of PC-1005 gel formulation (0.002%MIV-150/0.3% zinc acetate [ZA] in 3.0% carrageenan [CG] gel) when applied rectally
• To characterize the systemic and compartmental pharmacokinetics of MIV-150 following rectal gel application

Study Summary
MTN-037 was a Phase 1, open-label, sequential dose/volume escalation study designed to evaluate the safety and pharmacokinetics of PC-1005 (MIV-150/zinc acetate/carrageenan gel) when administered rectally. The study enrolled 12 healthy, HIV-uninfected men and women (cis or transgender) who are 18 years of age or older and who have a history of consensual receptive anal intercourse (RAI) will be enrolled in MTN-037. PC-1005 was designed to be a dual compartment gel (vaginal or rectal use), with potential activity against HIV-1, herpes simplex virus type 2 (HSV-2), and human papilloma virus (HPV). Study product was rectally administered by clinic staff. Each participant received a total of three doses of PC-1005 (1^st dose = 4mL, 2^nd dose = 16mL, and 3^rd dose = 32mL), with a 2-6-week washout period between each dose. Study endpoint assessments were performed within 24-48 hours of each of the three product applications. It was hypothesized that PC-1005 gel would be safe when applied to the rectum and well-tolerated among healthy men and women (cis or transgender). MTN-037 was the first study to assess the safety and PK of PC-1005 gel applied rectally.

The study completed follow-up on April 19, 2019. Primary results were presented at the HIV Research for Prevention (HIVR4P) conference held virtually on January 27-28 and February 3-4, 2021. Two abstracts have been published from this study. Primary and secondary manuscripts are in development.

Primary Results
We enrolled 13 participants, 7 men and 6 women (birth sex), median 34 years of age, including 6 white, 5 black, and 2 mixed race/ethnicity. Twelve participants completed all 3 doses. Thirteen adverse events were reported, all Grade 1 or 2, of which 5 were judged related to study drug without relationship to dose volume. Median (interquartile range) plasma MIV-150 concentration peaked 1 or 2 hours after dosing at 0.074 ng/mL (0.052, 0.086), 0.184 (0.162, 0.211), and 0.171 (0.098, 0.316), after 4, 16, and 32 mL doses, respectively; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Median half-life was 1.4-1.9 hours across dose volumes. Rectal Tissue MIV-150 peaked 0.5-1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume. Median tissue concentrations were BLQ (0.7 ng/g) at 1.5-3, 24, and 3.5-5 hours after each escalating dose volume, respectively. Median rectal fluid concentrations were >14 ng/mL (ng/g) through 5 hours in all arms; vaginal fluid samples were all BLQ (0.2 ng/mL). Across dose volumes, 83%-92% of participants rated the gel as comfortable or very comfortable.