A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study)
ABSTRACT Bemnifosbuvir is an oral antiviral drug with a dual mechanism of action targeting viral RNA polymerase, with in vitro activity against SARS-CoV-2. We conducted a phase 2, double-blind study evaluating the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulat...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00077-23 |
| _version_ | 1797741753798754304 |
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| author | Marta Boffito Eamon Dolan Karishma Singh William Holmes Steffen Wildum Arantxa Horga Keith Pietropaolo Xiao-Jian Zhou Barry Clinch Neil Collinson Vincent Ukachukwu |
| author_facet | Marta Boffito Eamon Dolan Karishma Singh William Holmes Steffen Wildum Arantxa Horga Keith Pietropaolo Xiao-Jian Zhou Barry Clinch Neil Collinson Vincent Ukachukwu |
| author_sort | Marta Boffito |
| collection | DOAJ |
| description | ABSTRACT Bemnifosbuvir is an oral antiviral drug with a dual mechanism of action targeting viral RNA polymerase, with in vitro activity against SARS-CoV-2. We conducted a phase 2, double-blind study evaluating the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulatory patients with mild/moderate COVID-19. Patients were randomized 1:1 to bemnifosbuvir 550 mg or placebo (cohort A) and 3:1 to bemnifosbuvir 1,100 mg or placebo (cohort B); all doses were given twice daily for 5 days. The primary endpoint was a change from baseline in the amount of nasopharyngeal SARS-CoV-2 viral RNA by reverse transcription PCR (RT-PCR). The modified intent-to-treat infected population comprised 100 patients (bemnifosbuvir 550 mg, n = 30; bemnifosbuvir 1,100 mg, n = 30; cohort A placebo, n = 30; cohort B placebo, n = 10). The primary endpoint was not met: the difference in viral RNA adjusted means at day 7 was −0.25 log10 copies/mL between bemnifosbuvir 550 mg and cohort A placebo (80% confidence interval [CI], −0.66 to 0.16; P = 0.4260), and −0.08 log10 copies/mL between bemnifosbuvir 1,100 mg and pooled placebo (80% CI, −0.48 to 0.33; P = 0.8083). Bemnifosbuvir 550 mg was well tolerated. Incidence of nausea and vomiting was higher with bemnifosbuvir 1,100 mg (10.0% and 16.7% of patients, respectively) than pooled placebo (2.5% nausea, 2.5% vomiting). In the primary analysis, bemnifosbuvir did not show meaningful antiviral activity on nasopharyngeal viral load as measured by RT-PCR compared with placebo in patients with mild/moderate COVID-19. The trial is registered at ClinicalTrials.gov under registration number NCT04709835. IMPORTANCE COVID-19 continues to be a major global public health challenge, and there remains a need for effective and convenient direct-acting antivirals that can be administered outside health care settings. Bemnifosbuvir is an oral antiviral with a dual mechanism of action and potent in vitro activity against SARS-CoV-2. In this study, we evaluated the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulatory patients with mild/moderate COVID-19. In the primary analysis, bemnifosbuvir did not show meaningful antiviral activity compared with placebo as assessed by nasopharyngeal viral loads. The negative predictive value of nasopharyngeal viral load reduction for clinical outcomes in COVID-19 is currently unclear, and further evaluation of bemnifosbuvir for COVID-19 may be warranted despite the findings observed in this study. |
| first_indexed | 2024-03-12T14:31:12Z |
| format | Article |
| id | doaj.art-4552e8053eae4486ab321c7d7c071f96 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-12T14:31:12Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-4552e8053eae4486ab321c7d7c071f962023-08-17T13:04:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.00077-23A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study)Marta Boffito0Eamon Dolan1Karishma Singh2William Holmes3Steffen Wildum4Arantxa Horga5Keith Pietropaolo6Xiao-Jian Zhou7Barry Clinch8Neil Collinson9Vincent Ukachukwu10Chelsea and Westminster Hospital NHS Foundation Trust London, United KingdomConnolly Hospital, Dublin, IrelandTower Family Healthcare, Bury, United KingdomRoche Products Ltd., Welwyn Garden City, United KingdomRoche Pharma, Research and Early Development, Roche Innovation Center Basel, Basel, SwitzerlandAtea Pharmaceuticals, Boston, Massachusetts, USAAtea Pharmaceuticals, Boston, Massachusetts, USAAtea Pharmaceuticals, Boston, Massachusetts, USARoche Products Ltd., Welwyn Garden City, United KingdomRoche Products Ltd., Welwyn Garden City, United KingdomRoche Products Ltd., Welwyn Garden City, United KingdomABSTRACT Bemnifosbuvir is an oral antiviral drug with a dual mechanism of action targeting viral RNA polymerase, with in vitro activity against SARS-CoV-2. We conducted a phase 2, double-blind study evaluating the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulatory patients with mild/moderate COVID-19. Patients were randomized 1:1 to bemnifosbuvir 550 mg or placebo (cohort A) and 3:1 to bemnifosbuvir 1,100 mg or placebo (cohort B); all doses were given twice daily for 5 days. The primary endpoint was a change from baseline in the amount of nasopharyngeal SARS-CoV-2 viral RNA by reverse transcription PCR (RT-PCR). The modified intent-to-treat infected population comprised 100 patients (bemnifosbuvir 550 mg, n = 30; bemnifosbuvir 1,100 mg, n = 30; cohort A placebo, n = 30; cohort B placebo, n = 10). The primary endpoint was not met: the difference in viral RNA adjusted means at day 7 was −0.25 log10 copies/mL between bemnifosbuvir 550 mg and cohort A placebo (80% confidence interval [CI], −0.66 to 0.16; P = 0.4260), and −0.08 log10 copies/mL between bemnifosbuvir 1,100 mg and pooled placebo (80% CI, −0.48 to 0.33; P = 0.8083). Bemnifosbuvir 550 mg was well tolerated. Incidence of nausea and vomiting was higher with bemnifosbuvir 1,100 mg (10.0% and 16.7% of patients, respectively) than pooled placebo (2.5% nausea, 2.5% vomiting). In the primary analysis, bemnifosbuvir did not show meaningful antiviral activity on nasopharyngeal viral load as measured by RT-PCR compared with placebo in patients with mild/moderate COVID-19. The trial is registered at ClinicalTrials.gov under registration number NCT04709835. IMPORTANCE COVID-19 continues to be a major global public health challenge, and there remains a need for effective and convenient direct-acting antivirals that can be administered outside health care settings. Bemnifosbuvir is an oral antiviral with a dual mechanism of action and potent in vitro activity against SARS-CoV-2. In this study, we evaluated the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulatory patients with mild/moderate COVID-19. In the primary analysis, bemnifosbuvir did not show meaningful antiviral activity compared with placebo as assessed by nasopharyngeal viral loads. The negative predictive value of nasopharyngeal viral load reduction for clinical outcomes in COVID-19 is currently unclear, and further evaluation of bemnifosbuvir for COVID-19 may be warranted despite the findings observed in this study.https://journals.asm.org/doi/10.1128/spectrum.00077-23AT-527COVID-19SARS-CoV-2bemnifosbuvirdirect-acting antiviral |
| spellingShingle | Marta Boffito Eamon Dolan Karishma Singh William Holmes Steffen Wildum Arantxa Horga Keith Pietropaolo Xiao-Jian Zhou Barry Clinch Neil Collinson Vincent Ukachukwu A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study) Microbiology Spectrum AT-527 COVID-19 SARS-CoV-2 bemnifosbuvir direct-acting antiviral |
| title | A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study) |
| title_full | A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study) |
| title_fullStr | A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study) |
| title_full_unstemmed | A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study) |
| title_short | A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study) |
| title_sort | phase 2 randomized trial evaluating the antiviral activity and safety of the direct acting antiviral bemnifosbuvir in ambulatory patients with mild or moderate covid 19 moonsong study |
| topic | AT-527 COVID-19 SARS-CoV-2 bemnifosbuvir direct-acting antiviral |
| url | https://journals.asm.org/doi/10.1128/spectrum.00077-23 |
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