Efficacy and Safety of Glecaprevir (ABT-493)/Pibrentasvir (ABT 530) (GLE/PIB) in Combination With Sofosbuvir and Ribavirin in Participants With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie Clinical Study

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of co-administration of glecaprevir (ABT-493)/pibrentasvir (ABT 530) plus sofosbuvir (SOF) plus ribavirin (RBV) in hepatitis C virus (HCV) genotype (GT) 1 - 6-infected participants (including non-cirrhotic, or cirrhotic with compensated cirrhosis participants) who had experienced virologic failure in an AbbVie parent clinical study.

Detailed Description
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This study enrolled HCV infected adults who had experienced virologic failure following treatment with glecaprevir/pibrentasvir or paritaprevir/ritonavir/ombitasvir + dasabuvir (DSV) (3D) or paritaprevir/ritonavir/ombitasvir (2D) regimens in one of the following AbbVie hepatitis C virus parent studies: M13-594 (NCT02640157) M13-596 (NCT02692703) M14-172 (NCT02642432) M14-242 (NCT02493855) M14-868 (NCT02243293) M15-410 (NCT02446717) M15-592 (NCT03222583) M16-126 (NCT02966795) M16-135 (NCT03089944)

Official Title
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An Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Combination With Sofosbuvir and Ribavirin in Chronic Hepatitis C (HCV) Infected Subjects Who Have Experienced Virologic Failure in AbbVie HCV Clinical Studies (MAGELLAN-3)

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: Sofosbuvir
* Drug: Glecaprevir/Pibrentasvir
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects must be adults (18 years of age or older) or adolescents (12 to less than 18 years of age weighing at least 35 kg). Subject must have experienced virologic failure during or after treatment with ABT-493/ABT-530 in an AbbVie HCV parent study. Subjects who have experienced virologic failure during or after receiving ombitasvir/paritaprevir/r + dasabuvir (3D), or ombitasvir/paritaprevir/r (2D) in an AbbVie HCV parent study may be enrolled at AbbVie's discretion. Treatment in the parent study must have been completed or discontinued at least 1 month prior to the Screening Visit. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements. Cirrhotic subjects must have compensated cirrhosis, (Child-Pugh score of ≤ 6) at Screening and no current or past evidence of Child-Pugh B or C Classification or no clinical history of liver decompensation, including ascites noted on physical exam, hepatic encephalopathy or esophageal variceal bleeding. Cirrhotic subjects must have absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound (US), computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to Screening or a negative US at Screening. Exclusion Criteria: History of severe, life-threatening or other clinically significant sensitivity to any study drug or drug component. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for 4 months after the last dose of study drug, or as directed per the local RBV label, whichever is more restrictive. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator. Positive test result at Screening for hepatitis B surface antigen (HBsAg). Screening laboratory analyses showing calculated creatinine clearance < 30 mL/min. Discontinuation from the AbbVie HCV parent study for reasons other than virologic failure (e.g., non-adherence, lost to follow-up, and/or the occurrence of an adverse event). Receipt of any HCV treatment after failing the treatment regimen in the AbbVie HCV parent study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glecaprevir/Pibrentasvir + SOF + RBV for 12 weeks<br>Participants without cirrhosis who had non-genotype 3 infection and were naïve to protease inhibitor (PI) and/or nonstructural viral protein 5A inhibitor (NS5Ai) prior to participation in AbbVie HCV parent study received daily treatment with glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg plus sofosbuvir (SOF) 400 mg plus twice-daily weight-based ribavirin (RBV) 600 mg - 1200 mg daily total for 12 weeks. | Drug: Sofosbuvir<br>* Tablet for oral administration<br>* Other names: SOVALDI;Drug: Glecaprevir/Pibrentasvir<br>* Coformulated tablet for oral administration<br>* Other names: MAVIRET;Drug: Ribavirin<br>* Tablet for oral administration<br>|
| Experimental: Glecaprevir/Pibrentasvir + SOF + RBV for 16 weeks<br>Participants with genotype 3, and/or compensated cirrhosis, and/or experience with PI and/or NS5Ai prior to participation in Abbvie HCV parent study received daily treatment with GLE/PIB 300 mg/120 mg plus SOF 400 mg plus twice-daily weight-based RBV 600 mg - 1200 mg daily total for 16 weeks. | Drug: Sofosbuvir<br>* Tablet for oral administration<br>* Other names: SOVALDI;Drug: Glecaprevir/Pibrentasvir<br>* Coformulated tablet for oral administration<br>* Other names: MAVIRET;Drug: Ribavirin<br>* Tablet for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as meeting one of the following: confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log10 IU/mL above nadir) at any time point during the treatment period; or confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA < 15 IU/mL during the treatment period, or HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment. | 12 or 16 weeks depending on the treatment regimen | 
| Percentage of Participants With Post-treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA greater than or equal to 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment 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. | From the end of treatment (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 or 28 depending on the treatment regimen). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C (HCV), HCV Genotype 1 (HCV GT1), HCV Genotype 2 (HCV GT2), HCV Genotype 3 (HCV GT3), HCV Genotype 4 (HCV GT4), HCV Genotype 5 (HCV GT5), HCV Genotype 6 (HCV GT6), Compensated Cirrhosis, Non-cirrhotics, Virologic failure