Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19
Despite effective vaccines and treatments for COVID-19, clinical burden persists. An unmet need exists for additional effective agents with safety profiles allowing use across a broad population. Ibuzatrelvir is an orally bioavailable SARS-CoV-2 Mpro inhibitor that has demonstrated in vitro antivira...
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creator | Mortezavi, Mahta Sloan, Abigail Singh, Ravi Shankar P Chen, Luke F Kim, Jin Hyang Shojaee, Negin Toussi, Sima S Prybylski, John Baniecki, Mary Lynn Bergman, Arthur Banerjee, Anindita Allerton, Charlotte Alami, Negar Niki |
description | Despite effective vaccines and treatments for COVID-19, clinical burden persists. An unmet need exists for additional effective agents with safety profiles allowing use across a broad population. Ibuzatrelvir is an orally bioavailable SARS-CoV-2 Mpro inhibitor that has demonstrated in vitro antiviral activity and low potential for safety concerns, including drug-drug interactions.
This phase 2b, double-blind, randomized clinical trial enrolled US adults aged 18‒ |
doi_str_mv | 10.1093/cid/ciae529 |
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This phase 2b, double-blind, randomized clinical trial enrolled US adults aged 18‒<65 years with symptomatic COVID-19 and no risk factors for severe disease. Participants were randomized 1:1:2:2 to receive 100, 300, or 600 mg ibuzatrelvir or placebo orally twice daily for 5 days. Nasopharyngeal specimens were collected on Days 1 (baseline), 3, 5, 10, 14, and 21; adverse events (AEs) were recorded through Day 33. The primary endpoint was change in SARS-CoV-2 RNA level (viral load [VL]) from baseline to Day 5 among participants with baseline VL ≥4 log10 copies/mL.
Of 240 enrollees, 237 received ≥1 dose and 199 were included in the primary analysis. Placebo-adjusted least squares mean (80% CI) change from baseline in VL at Day 5 was significant across all doses: 100 mg, ‒0.7 (‒1.1, ‒0.3) log10 copies/mL, P=0.02; 300 mg, ‒0.8 (‒1.3, ‒0.3) log10 copies/mL, P=0.01; and 600 mg, ‒1.2 (‒1.5, ‒0.8) log10 copies/mL, P<0.0001. AEs occurred in similar percentages of participants across groups. No deaths from any cause or treatment-related serious AEs occurred through Day 33, and no participants reported dysgeusia.
All 3 ibuzatrelvir doses were associated with robust antiviral activity and an acceptable safety profile, supporting continued clinical development.
Clinicaltrials.gov identifier: NCT05799495.</description><identifier>ISSN: 1058-4838</identifier><identifier>ISSN: 1537-6591</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciae529</identifier><identifier>PMID: 39486089</identifier><language>eng</language><publisher>United States</publisher><ispartof>Clinical infectious diseases, 2024-11</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39486089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mortezavi, Mahta</creatorcontrib><creatorcontrib>Sloan, Abigail</creatorcontrib><creatorcontrib>Singh, Ravi Shankar P</creatorcontrib><creatorcontrib>Chen, Luke F</creatorcontrib><creatorcontrib>Kim, Jin Hyang</creatorcontrib><creatorcontrib>Shojaee, Negin</creatorcontrib><creatorcontrib>Toussi, Sima S</creatorcontrib><creatorcontrib>Prybylski, John</creatorcontrib><creatorcontrib>Baniecki, Mary Lynn</creatorcontrib><creatorcontrib>Bergman, Arthur</creatorcontrib><creatorcontrib>Banerjee, Anindita</creatorcontrib><creatorcontrib>Allerton, Charlotte</creatorcontrib><creatorcontrib>Alami, Negar Niki</creatorcontrib><title>Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Despite effective vaccines and treatments for COVID-19, clinical burden persists. An unmet need exists for additional effective agents with safety profiles allowing use across a broad population. Ibuzatrelvir is an orally bioavailable SARS-CoV-2 Mpro inhibitor that has demonstrated in vitro antiviral activity and low potential for safety concerns, including drug-drug interactions.
This phase 2b, double-blind, randomized clinical trial enrolled US adults aged 18‒<65 years with symptomatic COVID-19 and no risk factors for severe disease. Participants were randomized 1:1:2:2 to receive 100, 300, or 600 mg ibuzatrelvir or placebo orally twice daily for 5 days. Nasopharyngeal specimens were collected on Days 1 (baseline), 3, 5, 10, 14, and 21; adverse events (AEs) were recorded through Day 33. The primary endpoint was change in SARS-CoV-2 RNA level (viral load [VL]) from baseline to Day 5 among participants with baseline VL ≥4 log10 copies/mL.
Of 240 enrollees, 237 received ≥1 dose and 199 were included in the primary analysis. Placebo-adjusted least squares mean (80% CI) change from baseline in VL at Day 5 was significant across all doses: 100 mg, ‒0.7 (‒1.1, ‒0.3) log10 copies/mL, P=0.02; 300 mg, ‒0.8 (‒1.3, ‒0.3) log10 copies/mL, P=0.01; and 600 mg, ‒1.2 (‒1.5, ‒0.8) log10 copies/mL, P<0.0001. AEs occurred in similar percentages of participants across groups. No deaths from any cause or treatment-related serious AEs occurred through Day 33, and no participants reported dysgeusia.
All 3 ibuzatrelvir doses were associated with robust antiviral activity and an acceptable safety profile, supporting continued clinical development.
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This phase 2b, double-blind, randomized clinical trial enrolled US adults aged 18‒<65 years with symptomatic COVID-19 and no risk factors for severe disease. Participants were randomized 1:1:2:2 to receive 100, 300, or 600 mg ibuzatrelvir or placebo orally twice daily for 5 days. Nasopharyngeal specimens were collected on Days 1 (baseline), 3, 5, 10, 14, and 21; adverse events (AEs) were recorded through Day 33. The primary endpoint was change in SARS-CoV-2 RNA level (viral load [VL]) from baseline to Day 5 among participants with baseline VL ≥4 log10 copies/mL.
Of 240 enrollees, 237 received ≥1 dose and 199 were included in the primary analysis. Placebo-adjusted least squares mean (80% CI) change from baseline in VL at Day 5 was significant across all doses: 100 mg, ‒0.7 (‒1.1, ‒0.3) log10 copies/mL, P=0.02; 300 mg, ‒0.8 (‒1.3, ‒0.3) log10 copies/mL, P=0.01; and 600 mg, ‒1.2 (‒1.5, ‒0.8) log10 copies/mL, P<0.0001. AEs occurred in similar percentages of participants across groups. No deaths from any cause or treatment-related serious AEs occurred through Day 33, and no participants reported dysgeusia.
All 3 ibuzatrelvir doses were associated with robust antiviral activity and an acceptable safety profile, supporting continued clinical development.
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title | Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19 |
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