CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

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An Injectable Multipurpose Implant With CAB and MPA for Long-Acting HIV Prevention and Contraception Ivana Massud 1 , Jasmine King 2 , Adam Vera 1 , Isabella Young 3 , Thy Le 3 , Jessica Levine 4 , James Mitchell 1 , Eric Edwards 1 , Mackenzie Cottrell 3 , Angela Kashuba 3 , Walid Heneine 1 , Gerardo Garcia-Lerma 1 , Rahima Benhabbour 3 , Charles Dobard 1 , Craig Sykes 3 1 Centers for Disease Control and Prevention, Atlanta, GA, USA, 2 CIDRZ / University of North Carolina, Chapel Hill, NC, USA, 3 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 4 Harvard Medical School, Boston, MA, USA Background: Prevention of HIV and unplanned pregnancies is a leading public health priority for women’s health. Multipurpose prevention technologies (MPTs) capable of delivering long-acting (LA) contraception and HIV prevention are needed. We recently demonstrated in-situ forming implants (ISFIs) in macaques can deliver cabotegravir (CAB) above protective benchmarks (>4 PA-IC 90 ) for more than 5 months. Here, we assessed in macaques an MPT CAB ISFI co-formulated with medroxyprogesterone acetate (MPA) and a contrast agent for in vivo visualization. We define long-term safety, PK, and efficacy on inhibiting ovulation and reversal of contraception by implant removal. Methods: Two 1-mL injections of ISFIs containing CAB (530 mg/mL), MPA (35 mg/mL) and 10% Barium-sulfate (BaSO4) were administered subcutaneously to 6 cycling pigtailed macaques. Plasma CAB, MPA, and progesterone were measured weekly for up to 6 months. ISFIs were surgically removed from 3 macaques at 3 months to assess contraceptive reversion. Implant site reactions were monitored using a modified Draize scale (0-4) and migration of ISFIs was assessed by X-ray imaging. Results: Only one animal showed injection site reaction at one implantation site (grade 3) that self-resolved within a week. Overall, CAB ISFIs co-formulated with BaSO4 elicited slightly lower CAB release in macaques, confirming in vitro and in vivo mouse data. Median (range) plasma CAB and MPA concentrations during the first 3 months were 668 (416-899) and 1.04 (0.43-2.58) ng/mL, respectively (Fig 1a). Progesterone was fully suppressed in all animals (Fig 1b). Removal of ISFIs in 3 animals at month 3 resulted in undetectable CAB and MPA concentrations within 1-2 weeks and return to ovulation within 3-5 weeks. In the 3 macaques that maintained ISFIs, plasma CAB and MPA concentrations at month 6 were 562 (421-1,046) and 0.33 (0.29-0.38) ng/mL, respectively, with no return to ovulation. None of the animals had evidence of implant migration by X-ray imaging. Conclusions: We report safety and long-term contraceptive efficacy of the first LA injectable MPT implant releasing CAB and MPA in macaques. Our findings showing a lack of implant migration are reassuring and suggest a limited value of adding BaSO4, particularly given the reduction in CAB release. Long-term suppression of ovulation after implantation and rapid reversal following removal suggest ISFIs may provide a discrete and flexible MPT option for adolescent girls and women.

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Ensitrelvir to Prevent COVID-19 in Households: SCORPIO-PEP Phase III Placebo-Controlled Trial Results Akimasa Fukushi 1 , Masaharu Shinkai 2 , Tristan W. Clark 3 , Annie F. Luetkemeyer 4 , Paul Sax 5 , William Hanage 6 , Kelly Gebo 7 , Hideyuki Ikematsu 8 , Koichi Izumikawa 9 , Christopher C. Butler 10 , Frederick G. Hayden 11 , Safwan Kezbor 12 , Hiroki Sakaguchi 1 , Norio Ohmagari 13 , Takeki Uehara 1 , for the SCORPIO-PEP Study Team 1 Shionogi & Co, Ltd, Osaka, Japan, 2 Tokyo Shinagawa Hospital, Shinagawa, Japan, 3 University of Southampton, Southampton, UK, 4 University of California San Francisco, San Francisco, CA, USA, 5 Brigham and Women's Hospital, Boston, MA, USA, 6 Harvard TH Chan School of Public Health, Boston, MA, USA, 7 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 8 Ricera Clinica Co, Fukuoka, Japan, 9 Nagasaki University, Nagasaki, Japan, 10 Oxford University, Oxford, UK, 11 University of Virginia, Charlottesville, VA, USA, 12 Shionogi & Co, Ltd, Florham Park, NJ, USA, 13 National Center for Global Health and Medicine, Tokyo, Japan Background: Ensitrelvir is an oral SARS-CoV-2 3CL protease inhibitor, approved in Japan for the treatment of mild-moderate COVID-19. No approved antivirals have been proven efficacious as post-exposure prophylaxis (PEP) in household contacts (HHC) of index patients (IP) with COVID-19. Methods: SCORPIO-PEP was a double-blind, placebo-controlled trial in HHC of IP with laboratory-confirmed COVID-19 conducted in the US, Japan, and other countries. HHC with negative local SARS-CoV-2 antigen or RT-PCR test were randomized 1:1 to receive either ensitrelvir (Day 1: 375mg, Day 2-5: 125mg), or placebo within 72 hours of symptom onset in the IP. The primary analysis population included HHC with central laboratory confirmed SARS-CoV-2 negativity by RT-PCR (mITT). The primary endpoint was the proportion of HHC who developed COVID-19 (RT-PCR positive and ≥1 of the 14 specified COVID-19 symptoms lasting for ≥48 hours) by Day 10. The secondary analysis population, which included HHC regardless of central laboratory RT-PCR results at baseline (ITT), was analyzed with the same endpoint. Results: Between June 2023 and August 2024, 2,389 HHC were enrolled, of whom 2,041 constituted mITT (ensitrelvir n=1,030 vs. placebo n=1,011). In the mITT, the mean age was 42.4 years, 71.1% of HHC were randomized within 48 hours of IP symptom onset, and 37.0% had ≥1 high-risk factor (HR) for severe COVID-19. In the mITT population, the overall proportion of HHC developing confirmed COVID-19 was significantly lower in the ensitrelvir group (2.9%) than in the placebo group (9.0%), with a risk ratio of 0.33 (95%CI: 0.22-0.49; p<0.0001). In the ITT population (ensitrelvir n=1,194 vs. placebo n=1,193), similar ensitrelvir efficacy was observed with a risk ratio of 0.43 (95%CI: 0.32 0.59; p<0.0001). In the HHC with baseline SARS-CoV-2 positivity (ensitrelvir n=114 vs. placebo n=123), the risk ratio was 0.75 (95%CI: 0.46-1.23). In the ensitrelvir and placebo groups, the proportions developing treatment-emergent adverse events (TEAEs) (15.1% vs. 15.5%, respectively) or serious TEAEs (0.2% vs. 0.2%) were similar, as were the TEAEs observed in >1.5% of patients in either group: headache (2.9% vs. 2.5%), diarrhea (1.8% vs. 1.3%) and influenza (1.1% vs. 1.6%). There were no COVID-19 related hospitalizations or fatalities. Conclusions: Administration of ensitrelvir to HHC <72 hours after the onset of IP symptoms was effective and generally well tolerated for PEP in HHC, including those with HR factors.

Oral Abstracts

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CROI 2025