Pre-clinical data show PC-1005 to be potent against HIV, HSV-2 and HPV when applied vaginally or rectally. Primary objectives of this study were to assess the safety and pharmacokinetics (PK) of PC-1005 (comprised of the NNRTI MIV-150 and zinc acetate [ZA] in a carrageenan [CG] gel). Acceptability, adherence, and pharmacodynamics were also explored.
20 healthy, abstinent women participated in a placebo-controlled, double-blind Phase 1 trial (RCT) at 1 US site, and were randomized (4:1) to apply 4 mL of PC-1005 or placebo vaginally once daily for 14d. The RCT was preceded by an open label safety run-in (OL) with 5 women applying PC-1005 once daily for 3d. Assessments included physical and pelvic exams, PK blood draws, safety labs, and colposcopy (with biopsies and cervicovaginal lavages [CVL] in the RCT). MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and CG (CVL) concentrations were measured with LCMS-MS, ICP-MS, and ELISA, respectively. Antiviral activity against HIV, HSV-2 and HPV in CVL was measured using cell-based assays. Adherence and acceptability were assessed quantitatively via paper-based questionnaires. Safety, acceptability and adherence data were analyzed descriptively. PK parameters were calculated using non-compartmental techniques and actual sampling times. EC50 values for CVL antiviral activity were calculated using a dose-response inhibition analysis.
All 5 participants completed the OL period and applied 3/3 doses. 17 participants completed the RCT, 2 were lost to follow up (1 never dosed), 1 withdrew before dosing, and 16 applied ≥ 93% of doses. Participants were 30 years old, on average (range 19-44) and 52% were Black or African American. Acceptability was high; 94% of participants reported willingness to use the gel in the future. AE rates, most of which were mild and/or unrelated, were similar in both gel groups. MIV-150 was absorbed systemically at low levels without accumulation (Table 1). Plasma zinc concentrations were unchanged from baseline. 7/7 CVLs collected 4h post-dose demonstrated measurable anti-HIV and anti-HPV activity. High antiviral activity in baseline CVLs precluded assessment of anti-HSV-2 activity in cell-based assays.
PC-1005 gel used vaginally for 14d was well-tolerated, with low systemic absorption of MIV-150, and measurable HIV and HPV antiviral activity in CVL. These results warrant continued development of PC-1005 as a viable vaginal or rectal microbicide for prevention of HIV and other STIs.