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 (MAGELLAN-3)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Hepatitis C Virus Infection

Treatments: Drug: Ribavirin; Drug: Glecaprevir/Pibrentasvir; Drug: Sofosbuvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02939989

2016-002491-26 (EudraCT Number)

M15-942

Details and patient eligibility

About

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.

Full description

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)

Enrollment: 33 patients

Sex: All

Ages: 12 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Glecaprevir/Pibrentasvir + SOF + RBV for 12 weeks

Experimental group

Description:

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.

Treatment:

Drug: Ribavirin

Drug: Sofosbuvir

Drug: Glecaprevir/Pibrentasvir

Glecaprevir/Pibrentasvir + SOF + RBV for 16 weeks

Experimental group

Description:

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.

Treatment:

Drug: Ribavirin

Drug: Sofosbuvir

Drug: Glecaprevir/Pibrentasvir