Journal Article

A first-in-human trial of MIV-150 and zinc acetate co-formulated in a carrageenan gel: Safety, pharmacokinetics, acceptability, adherence and pharmacodynamics

Objective
To evaluate the safety and pharmacokinetics (PK) of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics (PD) were also explored.

Design
A 3-day open label safety run-in (n=5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14d.

Methods
Assessments included physical exams, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LCMS-MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability and adherence were analyzed descriptively. PK parameters were calculated using non-compartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose-response inhibition analysis.

Results
Participants (n=20) ranged from 19-44 years old; 52% were Black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. 7/7 CVLs collected 4h post-dose demonstrated antiviral (HIV, HPV) activity. High baseline CVL anti-HSV-2 activity precluded assessment of post-dose activity.

Conclusion
PC-1005 used vaginally for 14d was well-tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Post-dose CVLs had anti-HIV and anti-HPV activity. These data warrant further development of PC-1005 for HIV and STI prevention.