A Study to Learn About the Study Medicines (Nirmatrelvir Plus Ritonavir) in People Aged 12 Years or Older With COVID-19 and a Compromised Immune System

Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called Nirmatrelvir/Ritonavir) for the possible treatment of COVID-19. Patients with COVID-19 who have more difficulty in fighting against infections have a higher chance of severe illness. Such patients may benefit from longer treatment durations compared to the standard treatment regimen. The study is seeking participants who: * Have a confirmed COVID-19 infection * Are Immunocompromised * Experience onset of signs/symptoms attributable to the current COVID-19 infection within 5 days prior to screening and ≥1 signs/symptoms attributable to COVID-19 present on the day of randomization. In addition, this study will also evaluate the efficacy and safety of a second treatment course of nirmatrelvir/ritonavir in people who experience that their COVID-19 is flaring up within 14 days of having taken a 5-day treatment course of nirmatrelvir/ritonavir. For this group, the study is seeking participants who: * Have a confirmed COVID-19 infection * Experience a worsening of signs/symptoms after completing an initial 5-day course of nirmatrelvir/ritonavir * The worsening of COVID-19 symptoms must occur within 14 days after completion of the initial 5-day course of nirmatrelvir/ritonavir * Are Immunocompromised * Experience onset of signs/symptoms attributable to the current COVID-19 infection within 48 hours prior to screening and ≥1 signs/symptoms attributable to COVID-19 present on the day of randomization. All participants will be taking the study medicine for either 5, 10, or 15 days. The study medication will be taken by mouth 2 times a day. Participants will take part in this study for about 24 weeks. The first dose of study medication is taken at the study site and the rest at home. Selected participants will need to visit the study site at least 10 times during the study.

Timeline

Start

2022-08-03

Primary completion

2023-07-17

Completion

2023-11-13

Publications

• Mokgokong R, Cislo P, Tudone E, Weinstein E, Cappelleri JC. Health-related quality of life in immunocompromised adults with mild-moderate COVID-19 treated with nirmatrelvir-ritonavir: results from the randomized, double-blinded EPIC-IC trial. Health Qual Life Outcomes. 2026 Mar 19;24(1):55. doi: 10.1186/s12955-026-02518-8.
• Mokgokong R, Cislo P, Tudone E, Weinstein E, Cappelleri JC. Symptom Alleviation/Resolution and Returns to Usual Health/Activities in Immunocompromised Adults with COVID-19 Treated with Nirmatrelvir-Ritonavir: Results from the EPIC-IC Trial. Infect Dis Ther. 2025 Dec;14(12):2763-2783. doi: 10.1007/s40121-025-01228-w. Epub 2025 Oct 14.
• Weinstein E, Paredes R, Gardner A, Almas M, Baniecki ML, Guan S, Tudone E, Antonucci S, Gregg K, Garcia-Vidal C, Camacho-Ortiz A, Wisemandle W, Terra SG, Liu S, Aberg JA, Rana MM, Corey L, Ford ES, Hammond J, Rusnak J. Extended nirmatrelvir-ritonavir treatment durations for immunocompromised patients with COVID-19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2025 Nov;25(11):1243-1253. doi: 10.1016/S1473-3099(25)00221-X. Epub 2025 Jul 14.
• Baniecki ML, Guan S, Rai DK, Yang Q, Lee JT, Hao L, Weinstein E, Hyde C, Cardin RD, Soares H, Hammond J. Integrated virologic analysis of resistance to nirmatrelvir/ritonavir in individuals across four phase 2/3 clinical studies for the treatment of COVID-19. EBioMedicine. 2025 Aug;118:105819. doi: 10.1016/j.ebiom.2025.105819. Epub 2025 Jun 30.

Drugs

Indications