CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

2-2-1-1, 2-2-2-1, and 2-2-2-2. PK modeling/simulation was performed in NONMEM v7.2, and R was used for synergy modeling and data management/ visualization. Results: Table 1 shows proportion achieving EC 90 in the FGT over time following sex. All regimens demonstrate >80% achievement of EC 90 at 5 days. A 2nd double-dose increases the proportion achieving EC 90 at 7 days by 20-30% compared to the IPERGAY regimen. Extending to 4 days of dosing increases the proportion achieving EC 90 >80% at 7 days post-sex. No regimen sustained this high proportion achieving EC 90 for 10 days post sex. Conclusions: Our model suggests prevention of HIV acquisition via the FGT using on-demand TDF/FTC dosing with an initial double-dose is likely, with high (>80%) protection for 5 days after sex. Adding a 4th day of dosing is required to achieve >80% protection for 7 days, with 2-2-2-2 at 95% and 2-1-1-1 at 84% protection. While limited data suggest 2-2-2-2 dosing is safe for short-term use, the 2-1-1-1 regimen may better balance safety, efficacy, and tolerability while maintaining effectiveness comparable to 4 daily doses/week reported by recent

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Host and Disease Factors Were Not Associated With Mpox Resolution in Participants Receiving Tpoxx William A. Fischer II 1 , Pooja Saha 2 , Jason Zucker 3 , Caitlyn McCarthy 2 , Lu Zheng 2 , Arzhang Javan 4 , Alexander L. Greninger 5 , Kristina Brooks 6 , Matthew Hamill 7 , Davey Smith 8 , Rajesh T. Gandhi 9 , Joseph J. Eron 1 , Sharon Nachman 10 , Judith Currier 11 , Timothy Wilkin 8 , for the ACTG A5418 (STOMP) Protocol Team 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Columbia University Irving Medical Center, New York, NY, USA, 4 National Institutes of Health, Bethesda, MD, USA, 5 University of Washington, Seattle, WA, USA, 6 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 7 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 8 University of California San Diego, La Jolla, CA, USA, 9 Harvard Medical School, Boston, MA, USA, 10 Stony Brook University, Stony Brook, NY, USA, 11 University of California Los Angeles, Los Angeles, CA, USA Background: ACTG A5418/STOMP is a phase 3 randomized placebo-controlled double-blind trial evaluating the efficacy of tecovirimat in people with mpox. It includes an open-label arm for people <18 years, pregnant or breastfeeding, with severe immune suppression, or protocol-defined severe disease. We analyzed host and disease factors associated with clinical mpox resolution and mpox DNA clearance from skin lesions in individuals receiving open-label tecovirimat for 14 days. Methods: Time to clinical resolution was the time from treatment initiation until all skin lesions were scabbed, desquamated, or healed and all visible mucosal lesions were healed through 28 days. An index skin lesion chosen at enrollment was swabbed weekly; mpox DNA levels were measured by PCR. Associations between baseline characteristics and time to clinical resolution were explored using Kaplan-Meier plots and Cox proportional hazards models. Results: Of 233 enrolled in the open-label arm, 107 had lab-confirmed clade II mpox (skin, oral or rectal swabs) who enrolled early enough to have completed 28-day follow-up and had baseline skin lesion mpox DNA available were included. Ninety-six (90%) were cisgender male, 3 (3%) were transgender female, median age was 34 years, 45 (42%) are living with HIV, including 11 with CD4 <200 cells/mm 3 or HIV-1 RNA >1000 copies/ml, and 12 (11%) had previously received ≥1 dose of the smallpox/mpox vaccine. At enrollment, median skin lesion count was 26 (IQR: 13, 49), 78 (73%) had >5 days of symptoms at time of enrollment, and 11 (10%) had undetectable skin lesion mpox DNA. By Days 8 and 15, 47% (of 76) and 82% (of 77) had undetectable skin lesion mpox DNA. The cumulative probability of clinical resolution by 28 days was 86% (95% CI: 79, 92); median days to clinical resolution was 14 (Q1, Q3: 8, 22). While there were trends between faster clinical resolution, lower levels of mpox DNA, and

Oral Abstracts

analyses of PrEP clinical trial data. The 2-2-2, 2-1-1-1, and 2-2-1-1 regimens could be considered in future clinical studies of on-demand PrEP in cisgender women. Safety and Antiviral Efficacy of a Broad-Spectrum siRNA SNS812 Targeting SARS-CoV-2: Phase II Trial Sui-Yuan Chang 1 , Yi-Chung Chang 2 , Shey-Ying Chen 3 , Pan-Chyr Yang 1 1 National Taiwan University, Taipei, Taiwan, 2 Oneness Biotech Co, Ltd, Taipei City, Taiwan, 3 National Taiwan University Hospital, Taipei, Taiwan Background: The rapid emergence of immune-evasive SARS-CoV-2 variants poses a significant challenge, as current therapies and vaccines struggle to keep pace. SNS812, an aerosolized broad-spectrum antiviral siRNA, targets a conserved region of the RNA-dependent RNA polymerase gene, unchanged since the 2003 SARS outbreak, offering potential efficacy against diverse variants. In a 2023 Phase I trial (NCT05677893) in the U.S., SNS812 showed excellent safety. Here we present the Phase II trial results which shows SNS812 is safe and effective in treating COVID-19. Methods: This double-blind, randomized, placebo-controlled Phase II trial (NCT05941793) involved 135 symptomatic, PCR-confirmed COVID-19 patients, all vaccinated at least three months prior. Participants were randomly assigned to receive either 100mg SNS812, 200mg SNS812, or placebo. The primary endpoint was the incidence of treatment-emergent adverse events; efficacy endpoints included viral variant analysis, time to viral clearance, viral load reduction, and symptoms improvement. Results: Baseline characteristics showed no significant differences between the groups. No drug-related adverse events were observed in the SNS812 treatment groups. All 135 participants had their viral sequence confirmed and identified which revealed that 90% of patients were infected with highly immune-evasive variants, with the majority being JN.1 (49.6%), LB.1 (17.1%), and KP.2 (11.1%). Viral load analysis showed that in the SNS812 treatment groups, viral load significantly decreased by 0.4 log within one day of SNS812 200mg administration (P=0.029). Additionally, the median time to viral clearance was reduced from 3.6 days (control group) to 2.9 days (200mg group)(P=0.007). For clinically meaningful symptoms, 12 out of 14 COVID-19 symptoms showed improvements, with key symptoms such as shortness of breath (P=0.007), loss of smell (P=0.028), and loss of taste (P=0.006) achieving statistical significance. Furthermore, a dose-dependent relationship was noted, with more significant improvement in 200mg group compared to the 100mg. Conclusions: The Phase II study demonstrates that SNS812 is a safe and effective treatment for COVID-19, especially in the context of immune-evasive variants. Its ability to significantly reduce viral load within one day, accelerate viral clearance, and improve symptoms positions SNS812 as a promising pan-coronavirus therapeutic solution, capable of addressing ongoing viral mutations.

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CROI 2025