Study to Evaluate Adverse Events and Change in Disease Activity in Adult and Adolescent Participants With Acute Hepatitis C Virus (HCV) Infection on Treatment With Oral Tablets of Glecaprevir (GLE)/Pibrentasvir (PIB)

• Glecaprevir/Pibrentasvir (GLE/PIB) (Drug), also known as ABT-493/ABT-530, Mavyret: Oral tablets

Primary outcomes

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in the Intention-to-Treat (ITT) Population [12 weeks after last dose of study treatment (Week 20)]: SVR12 is defined as the hepatitis C virus (HCV) ribonucleic acid (RNA) level less than the lower limit of quantification (< LLOQ) 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 90.5%.

Secondary outcomes

• Percentage of Participants Achieving SVR12 in the Modified ITT-Virologic Failure (mITT-VF) Population [12 weeks after last dose of study treatment (Week 20)]: SVR12 is defined as the HCV RNA level < LLOQ 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 92.7%. This efficacy analysis was performed only if success was demonstrated for the primary efficacy analysis, following a fixed-sequence testing procedure.
• Percentage of Participants With On-Treatment Virologic Failure in the ITT Population [Up to Week 8]: On-treatment virologic failure is defined as confirmed increase in HCV RNA of > 1 log\^10 IU/mL above the lowest post-baseline value during treatment, confirmed HCV RNA >= 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA >= LLOQ at the end of treatment (EOT) with at least 6 weeks of treatment.
• Percentage of Participants With Post-Treatment (PT) Relapse in the ITT Population [Up to 12 weeks after the last dose of study treatment (Week 20)]: PT relapse is defined as confirmed HCV RNA >= LLOQ between the EOT and 12 weeks after the last dose of study treatment among participants who completed treatment as planned (study treatment duration >= 52 days) with HCV RNA < LLOQ at the EOT and with at least 1 PT HCV RNA value, excluding cases of reinfection.
• Percentage of Participants With PT Reinfection With HCV in the ITT Population [Up to 12 weeks after the last dose of study treatment (Week 20)]: PT reinfection is defined as confirmed HCV RNA >= LLOQ in the PT period in a participant who had HCV RNA < LLOQ at the final treatment visit, along with the PT detection of a different HCV genotype, subtype, or clade compared with baseline.

Sex: All, ages: 12 Years to any

Inclusion Criteria:

* Evidence of acute HCV infection prior to enrollment, defined as a physician diagnosis of acute HCV infection, quantifiable HCV ribonucleic Acid (RNA) at screening, and at least 1 of the following:

  * Negative anti-HCV antibody, HCV RNA and/or HCV core antigen followed by a positive HCV RNA or HCV core antigen all within an 8-month period prior to screening; OR
  * Negative anti-HCV antibody, HCV RNA and/or HCV core antigen followed by a positive HCV RNA or HCV core antigen all within an 11-month period prior to screening; AND risk behavior for HCV infection within 6 months prior to positive HCV RNA or HCV core antigen; OR
  * Clinical signs and symptoms compatible with acute hepatitis \[alanine aminotransferase (ALT) > 5 × upper limit of normal (ULN) and/or jaundice\] in the absence of a history of chronic liver disease or other cause of acute hepatitis and positive HCV RNA or HCV core antigen all within an 8-month period prior to screening; AND risk behavior for HCV infection within 6 months prior to positive HCV RNA or HCV core antigen; OR
  * Negative anti-HCV antibody with a positive HCV RNA or HCV core antigen within a 5-month period prior to screening.
* Absence of hepatocellular carcinoma (HCC), for participants with cirrhosis, or with indeterminate cirrhosis status, as indicated by a negative ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to screening or a negative ultrasound at screening. Participant who has a positive ultrasound result suspicious of HCC followed by a subsequent negative CT scan or MRI or biopsy result will be eligible for the study.
* Participants documented as having no cirrhosis or as having compensated cirrhosis.

Exclusion Criteria:

* Participants with prior treatment, including interferon for this HCV infection.
* History of liver decompensation.

Participant flow

Outcome results

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in the Intention-to-Treat (ITT) Population (Primary), Number, percentage of participants: Glecaprevir/Pibrentasvir 96.2 (93.2 to 97.8)
• Percentage of Participants Achieving SVR12 in the Modified ITT-Virologic Failure (mITT-VF) Population (Secondary), Number, percentage of participants: Glecaprevir/Pibrentasvir 100 (98.6 to 100.0)
• Percentage of Participants With On-Treatment Virologic Failure in the ITT Population (Secondary), Number, percentage of participants: Glecaprevir/Pibrentasvir 0 (0.0 to 1.3)
• Percentage of Participants With Post-Treatment (PT) Relapse in the ITT Population (Secondary), Number, percentage of participants: Glecaprevir/Pibrentasvir 0 (0.0 to 1.4)
• Percentage of Participants With PT Reinfection With HCV in the ITT Population (Secondary), Number, percentage of participants: Glecaprevir/Pibrentasvir 0.7 (0.2 to 2.5)

Adverse events

Time frame: Screening (Day -30) through Post-treatment Week 12 (Week 20) or premature discontinuation.

Serious adverse events by term

Other adverse events by term

• Results publication: Boesecke C, Workowski K, Gordon SC, Cave B, Marcinak J, Miller MG, Semizarov D, Welhaven A, Baumgarten A. Glecaprevir/Pibrentasvir for Acute Hepatitis C Virus Infection in Individuals with a History of Prior Hepatitis C Infection. Infect Dis Ther. 2026 Sep;15(9):2319-2334. doi: 10.1007/s40121-026-01381-w. Epub 2026 Jun 24. PMID 42340583
• Results publication: Llibre JM, Boesecke C, Moon J, Lank PM, Miller MG, Fredrick LM, Welhaven A, Semizarov D, Marcinak J, Gentile I, Reiberger T, Puoti M. A single-arm phase IIIb study of 8-week glecaprevir/pibrentasvir treatment in adults with acute hepatitis C. J Hepatol. 2026 Apr;84(4):702-712. doi: 10.1016/j.jhep.2025.11.009. Epub 2025 Nov 24. PMID 41297677

• Study Protocol (PDF, 2022-08-26)
• Statistical Analysis Plan (PDF, 2024-08-12)

• ABBVIE INC., Study director, AbbVie