A Phase I Randomized Placebo Controlled Trial of the Safety of 3% SPL7013 Gel (VivaGel®) in Healthy Young Women Administered Twice Daily for 14 Days

Abstract

ObjectiveTo assess the safety of VivaGel® used vaginally twice daily for 14 days among healthy, sexually-abstinent women, aged 18–24 years in the USA and Kenya.DesignRandomized placebo controlled trial.MethodsParticipants were randomized 2∶1, VivaGel to placebo. Safety was assessed by comparing genitourinary (GU) adverse events (AEs), colposcopy findings, vaginal lactobacilli and laboratory abnormalities by arm.ResultsFifty-four women were enrolled; 35 in the VivaGel arm and 19 in the placebo arm. Twenty-six (74%) and 10 (53%) women reported taking all doses of VivaGel and placebo, respectively. No grade 3 or 4 AEs, or serious AEs occurred. Twenty-five (71%) participants in the VivaGel arm compared to 10 (53%) participants in the placebo arm had at least one grade 1 or 2 GU AE associated with product use (RR = 1.4, 95% CI 0.8-2.2). All seven grade 2 GU AEs associated with product use occurred among four women in the VivaGel arm. Vulvar and cervical erythema, cervical lesions, symptomatic BV, urinary frequency and metrorrhagia were more common in the VivaGel arm than the placebo arm. Twenty-nine (83%) participants in the VivaGel arm had a colposcopic finding compared to 10 (53%) participants in the placebo arm (RR = 1.6, 95%CI = 1.0-2.5). Two women in the VivaGel arm prematurely discontinued product use themselves due to a reported GU AE. Persistence of H2O2-producing and non-producing lactobacilli did not differ by study arm.ConclusionsGU AEs and colposcopic findings consistent with mild epithelial irritation and inflammation occurred more commonly among women in the VivaGel arm.Trial RegistrationClinicalTrials.gov NCT003311032

Clinical Translation of Nanomedicine

“…A second phase I study attempted increasing to twice daily administration of 3% gel. 311 Again, this was fairly well tolerated but mild symptoms were more frequently reported in the Vivagel than control groups (71% vs 53%) as were more frequent mild colposcopic irregularities (83% vs 53%) including cervical erythema. The latter observation is quite concerning as any degree of mucosal breakdown or lymphocyte recruitment could be potentially problematic as loss of mucosal integrity could favor viral transmission.…”

Phosphorus-containing dendrimers against α-synuclein fibril formation

“…The product has an inhibitory effect on human deficiency virus (HIV), herpes simplex virus (HSV) and may be used for treatment of bacterial vaginosis [6][7][8].…”

Semen-mediated Enhancement of HIV Infection Markedly Impairs the Antiviral Efficacy of Microbicides

“…Meanwhile, further development of polyanions and SPL7013 as microbicides was halted as a result of higher incidences of HIV-1 infection. The higher susceptibility was due to toxic effects that led to local inflammation in the female genital tract [29,83,84,145].…”