Efficacy and safety of a self-applied carrageenan-based gel to prevent human papillomavirus infection in sexually active young women (CATCH study): an exploratory phase IIB randomised, placebo-controlled trial

BACKGROUND: Carrageenan demonstrated potent anti-HPV (human papillomavirus) activity in vitro and in animal models. The Carrageenan-gel Against Transmission of Cervical Human papillomavirus trial’s interim analysis (n = 277) demonstrated a 36% protective effect of carrageenan against incident HPV infections. Herein, we report the trial’s final results. METHODS: In this exploratory phase IIB randomised, placebo-controlled trial, we recruited healthy women aged ≥18 years primarily from health service clinics at two Canadian Universities in Montreal. Participants were randomised (1:1) by the study coordinator (using computer-assisted block randomisation with randomly variable block sizes up to a block size of eight) to a carrageenan-based or placebo gel to be self-applied every other day for the first month and before/after intercourse. Participants, study nurses, and laboratory technicians (HPV testing and genotyping) were blinded to group assignment. At each visit (months 0, 0.5, 1, 3, 6, 9, 12), participants provided questionnaire data and a self-collected vaginal sample (tested for 36 HPV types, Linear Array). The primary outcome was type-specific HPV incidence (occurring at any follow-up visit). Intention-to-treat analyses for incidence were conducted using Cox proportional hazards regression models, including participants with ≥2 visits. Safety analyses included all participants randomised. This trial is registered with the ISRCTN registry, ISRCTN96104919. FINDINGS: Between Jan 16, 2013 and Sept 30, 2020, 461 participants (enrolled) were randomly assigned to the carrageenan (n = 227) or placebo (n = 234) groups. Incidence and safety analyses included 429 and 461 participants, respectively. We found 51.9% (108/208) of participants in carrageenan and 66.5% (147/221) in placebo arm acquired ≥1 HPV type (hazard ratio 0.63 [95% CI: 0.49–0.81], p = 0.0003). Adverse events were reported by 34.8% (79/227) and 39.7% (93/234) of participants in carrageenan and placebo arm (p = 0.27), respectively. INTERPRETATION: Consistent with the interim analysis, use of a carrageenan-based gel compared to placebo resulted in a 37% reduction in risk of incident genital HPV infections in women with no increase in adverse events. A carrageenan-based gel may complement HPV vaccination. FUNDING: 10.13039/501100000024Canadian Institutes of Health Research, CarraShield Labs Inc.