- 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
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 (1st dose = 4mL, 2nd dose = 16mL, and 3rd 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.
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.
US Eunice Kennedy Shriver National Institute of Child Health and Human Development
US National Institute of Mental Health
US National Institutes of Health
Phase 1, open label, sequential dose/volume escalation trial