Phase I dose volume escalation of rectally administered PC-1005 to assess safety, pharmacokinetics, and antiviral pharmacodynamics as a multipurpose prevention technology (MTN-037)
Document Type
Article (peer-reviewed)
Publication Date
8-13-2024
Abstract
Background: On demand, topical PrEP is desired by those preferring episodic, non-systemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, HPV, and HSV-2 activity, attractive for a multipurpose prevention technology (MPT) candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally-applied PC-1005. Methods: HIV-uninfected adults received a series of three rectal PC-1005 doses - 4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 h. Results: Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were Grade 1 or 2; five were judged study drug-related. Plasma MIV-150 peaked 1-2 h after dosing with a median peak concentrations range of 0.07-0.23 ng/mL and median half-life range of 4.9-7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 h after dosing. 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 beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 h of antiviral HPV and HSV effect, but no anti-HIV activity. Conclusions: MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects, but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as an MPT candidate.
Recommended Citation
Ho, Ken Ho, Craig Hoesley, Peter L. Anderson, José Fernández-Romero, Barbara Friedland, et al. on behalf of the MTN-037 Study Team. 2024. "Phase I dose volume escalation of rectally administered PC-1005 to assess safety, pharmacokinetics, and antiviral pharmacodynamics as a multipurpose prevention technology (MTN-037)," Journal of Acquired Immune Deficiency Syndromes, 10.1097/QAI.0000000000003506.
DOI
10.1097/QAI.0000000000003506
Language
English
http://doi.org/10.1097/QAI.0000000000003506