Results of the phase 1, randomized, placebo-controlled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel

Griffithsin (GRFT) is an anti-viral lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after topical administration, and lack of cross-resistance with existing products prompted its development for topical HIV pre-exposure prophylaxis. We evaluated safety, pharmacokinetics and pharmacodynamics of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy, HIV-negative, non-pregnant women following once daily vaginal gel administration for 14 days. No significant adverse events, histopathological changes in cervico-vaginal mucosa, or anti-drug (GRFT) antibodies were detected. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Vaginal microbiome remained largely unchanged. Reduced abundance of vaginosis-associated bacteria and decreased levels of proinflammatory chemokines (CXCL8 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in CVLs dose-dependently inhibited HIV and HPV, respectively, in vitro. The data suggest GRFT/CG is a promising on-demand multipurpose prevention product that warrants further investigation. Ectocervical biopsies from 12 subjects collected before exposure to gel (baseline, BL) and 24h after last gel administration. Total 24 samples.