A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection

AbbVie

Status and phase: Completed; Phase 3; Phase 2

Conditions: Hepatitis C Virus; Chronic Hepatitis C

Treatments: Drug: ABT-530; Drug: ABT-493/ABT-530; Drug: ABT-493; Drug: ribavirin (RBV)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02243293

M14-868

2014-002927-90 (EudraCT Number)

Details and patient eligibility

About

The purpose of this phase 2/3, open-label, multipart, multicenter study was to evaluate the efficacy, and safety of co-administration of ABT-493 and ABT-530 with and without ribavirin (RBV) in chronic HCV genotype 2 (GT2-), genotype 3 (GT3-), genotype 4 (GT4), genotype 5 (GT5-), or genotype 6 (GT6-) infected participants with or without cirrhosis.

Full description

The study consisted of four independent parts with treatment and post-treatment periods of enrollment. Parts 1 and 2 were the supportive/ exploratory parts (phase 2) of the study and part 3 and 4 were the confirmatory/ registrational parts (phase 3) of the study. In parts 1 and 2 of the study, ABT-493 and ABT-530 were co-administered as separate tablets. However, in parts 3 and 4 of the study, the ABT-493/ABT-530 co-formulated tablets were administered.

Enrollment: 694 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Screening laboratory result indicating HCV Genotype 2, 3, 4, 5, or 6 infection.
• Chronic HCV infection.
• Participant had to be either HCV treatment-naïve or treatment-experienced.
• Participant had to be documented as non-cirrhotic or as having compensated cirrhosis (GT3 only).

Exclusion criteria

• History of severe, life-threatening or other significant sensitivity to any drug.
• Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study.
• 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) or anti-human immunodeficiency virus antibody (HIV Ab).
• HCV genotype performed during screening indicating co-infection with more than one HCV genotype.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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694 participants in 22 patient groups

Arm A

Experimental group

Description:

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 2 (GT2) -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm B

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm C

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided twice daily (BID) for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ribavirin (RBV)

Drug: ABT-530

Arm D

Experimental group

Description:

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 3 (GT3) -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm E

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm F

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided BID for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ribavirin (RBV)

Drug: ABT-530

Arm G

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm H

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm I

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm J

Experimental group

Description:

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm K

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm L

Experimental group

Description:

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm M

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm N

Experimental group

Description:

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD and ribavirin (RBV) (800 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis.

Treatment:

Drug: ABT-493

Drug: ribavirin (RBV)

Drug: ABT-530

Arm O

Experimental group

Description:

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis and for 16 weeks in HCV GT3 -infected treatment-experienced participants with compensated cirrhosis.

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm P

Experimental group

Description:

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and RBV (800 mg) QD for 12 weeks in HCV GT3-infected treatment naïve and treatment-experienced participants with compensated cirrhosis.

Treatment:

Drug: ABT-493

Drug: ribavirin (RBV)

Drug: ABT-530

Arm Q1

Experimental group

Description:

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment naïve participants with cirrhosis.

Treatment:

Drug: ABT-493/ABT-530

Arm Q2

Experimental group

Description:

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493/ABT-530

Arm R1

Experimental group

Description:

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493/ABT-530

Arm R2

Experimental group

Description:

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants with cirrhosis.

Treatment:

Drug: ABT-493/ABT-530

Arm S1

Experimental group

Description:

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT2 infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493/ABT-530

Arm S2

Experimental group

Description:

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT4-6 infected treatment naïve and treatment experienced participants without cirrhosis.

Treatment:

Drug: ABT-493/ABT-530