A Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment-Naive Adults in Brazil With Chronic Hepatitis C Virus (HCV) Genotype 1 - 6 Infection

This was a Phase 3, open-label, multicenter study to evaluate the efficacy and safety of GLE/PIB for an 8- or 12-week treatment duration in adults in Brazil with chronic HCV GT1 to GT6 infection, without cirrhosis or with compensated cirrhosis with a METAVIR System Fibrosis Score of F2 to F3 (without cirrhosis) or F4 (with compensated cirrhosis) or equivalent, who were HCV treatment-naïve.

• Glecaprevir/Pibrentasvir (Drug), also known as ABT-493, ABT-530, MAVYRET: Film-coated tablet

Primary outcomes

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after last dose of study drug (week 20 or 24 depending on treatment regimen)]: SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug.

Secondary outcomes

• Percentage of Participants With On-treatment HCV Virologic Failure [8 or 12 weeks (depending on treatment regimen)]: On-treatment HCV virologic failure was defined as one of the following: * Confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ 100 IU/mL after HCV RNA < 15 IU/mL at any time point during treatment; or * Confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log10 IU/mL above nadir) during study drug treatment; or * HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment.
• Percentage of Participants With Post-treatment HCV Virologic Relapse [From the end of treatment (8 or 12 weeks depending on treatment regimen) through 12 weeks after the last dose of study drug]: Post-treatment HCV virologic relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA levels < 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Participant had positive plasma hepatitis C virus (HCV) antibody and HCV ribonucleic acid (RNA) viral load greater than or equal to 1000 IU/mL at Screening Visit.
* Participant must have been documented as without cirrhosis with METAVIR equivalent fibrosis stage of F2 to F3 or with compensated cirrhosis (F4) based on results of a liver biopsy, or FibroScan, or FibroTest score.
* Participants who were known to be HCV/Human Immunodeficiency Virus (HIV) co-infected may have been enrolled if they had a positive test result for anti-HIV antibody at Screening and were: naïve to treatment with any antiretroviral therapy (ART), or on a stable, qualifying HIV ART regimen for at least 8 weeks prior to Baseline.
* Participants with compensated cirrhosis only: Absence of hepatocellular carcinoma (HCC) within 3 months prior to Screening or a negative ultrasound at Screening.

Exclusion Criteria:

* Current hepatitis B virus (HBV) infection on screening tests.
* Any current or past clinical evidence of Child-Pugh B or C classification (score of > 6) or clinical history of liver decompensation including ascites on physical exam, including hepatic encephalopathy or variceal bleeding.
* Receipt of any investigational or commercially available anti-HCV agents.

Participant flow

Outcome results

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) (Primary), Number, percentage of participants: All Participants 98.0 (93.0 to 99.4)
• Percentage of Participants With On-treatment HCV Virologic Failure (Secondary), Number, percentage of participants: All Participants 0 (0.0 to 3.7)
• Percentage of Participants With Post-treatment HCV Virologic Relapse (Secondary), Number, percentage of participants: All Participants 1.0 (0.2 to 5.4)

Adverse events

Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug.

Serious adverse events by term

Other adverse events by term

• Results publication: Brown RS Jr, Collins MA, Strasser SI, Emmett A, Topp AS, Burroughs M, Ferreira R, Feld JJ. Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension. Infect Dis Ther. 2022 Apr;11(2):913-924. doi: 10.1007/s40121-022-00599-8. Epub 2022 Feb 17. PMID 35174470
• Results publication: Peribanez-Gonzalez M, Cheinquer H, Rodrigues L, Lima MP, Alvares-da-Silva MR, Madruga J, Parise ER, Pessoa MG, Furtado J, Villanova M, Ferreira A, Mazzoleni F, Nascimento E, Silva GF, Fredrick L, Krishnan P, Burroughs M, Reuter T. Efficacy and safety of glecaprevir/pibrentasvir in treatment-naive adults with chronic hepatitis C virus genotypes 1-6 in Brazil. Ann Hepatol. 2021 Jan-Feb;20:100257. doi: 10.1016/j.aohep.2020.09.002. Epub 2020 Sep 17. PMID 32949786

• Study Protocol (PDF, 2018-08-02)
• Statistical Analysis Plan (PDF, 2019-01-29)

• AbbVie Inc., Study director, AbbVie