A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-administration of ABT-493 and ABT-530 With and Without Ribavirin in Subjects With HCV Genotype 1, 4, 5, and 6 Infection

AbbVie

Status and phase

Completed

Phase 2

Conditions

HCV

Hepatitis C Virus

Chronic Hepatitis C

Treatments

Drug: ABT-530

Drug: ABT-493

Study type

Interventional

Funder types

Industry

Identifiers

NCT02243280

M14-867

2014-002925-36 (EudraCT Number)

Details and patient eligibility

About

The purpose of this Phase 2, open-label, 2-part, multicenter study was to evaluate the efficacy, safety, and pharmacokinetics of co-administration of ABT-493 and ABT-530 with and without ribavirin (RBV) at different doses in chronic Hepatitis C virus (HCV) Genotype 1 (GT1), Genotype 4 (GT4), Genotype 5 (GT5), and Genotype 6 (GT6) infection with compensated cirrhosis (GT1 only) or without cirrhosis (GT1, GT4, GT5, or GT6). Although RBV was initially planned in the protocol, it was not administered in any of the study arms.

Full description

This study consisted of two independent parts: Part 1 was conducted first followed by Part 2. Part 1 enrolled participants who received ABT-493 and ABT-530 for 12 weeks; Part 2 enrolled participants who received ABT-493 and ABT-530 for 8 or 12 weeks. Participants who completed or prematurely discontinued the treatment period were followed for 24 weeks to monitor HCV RNA to evaluate efficacy and the emergence and persistence of viral variants.

Enrollment

174 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female between 18 and 70 years of age, inclusive, at time of screening
Screening laboratory result indicating hepatitis C virus (HCV) GT1 (Study Parts 1 and 2) or GT4, GT5, or GT6 (Study Part 2) infection
Chronic HCV infection defined as one of the following:
- Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening, and positive for HCV RNA and anti-HCV Ab at the time of screening or
- Positive for anti-HCV Ab and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of chronic HCV infection)
Participant had to meet one of the following criteria:
- Treatment-naïve: participant had never received treatment for HCV infection
- Treatment-experienced: pegylated-interferon alpha-2a or alpha-2b and ribavirin (PR)-null responder (for Study Part 1) or PR-experienced (on-treatment failure or prior relapse) (for Study Part 2)
Documented absence of cirrhosis (in Study Part 1 and in corresponding arms of Study Part 2), or compensated cirrhosis (in corresponding arms of Study Part 2, GT1 only), per local standard

Exclusion criteria

History of severe, life-threatening or other significant sensitivity to any drug
Female who is pregnant, planning to become pregnant during the study or breastfeeding; or male whose partner is 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)
Hepatitis C virus (HCV) genotype performed during screening indicating co-infection with more than one HCV genotype
Any cause of liver disease other than chronic HCV infection
Participants with plasma HCV RNA load ≤ 10,000 international units (IU)/mL or unquantifiable or undetectable HCV RNA at screening
Previous use of an HCV direct-acting antiviral agent (DAA)
Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493, ABT-530, or RBV (RBV for cirrhotic subjects only)
For participants in Study Part 2 who were enrolling with compensated cirrhosis: past clinical evidence of Child-Pugh B or C Classification (score of > 6) or clinical history of liver decompensation, including ascites (noted on physical exam), bleeding varices, use of beta-blockers for portal hypertension or ascites, or hepatic encephalopathy

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

174 participants in 11 patient groups

Arm A

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD for 12 weeks in HCV genotype 1-infected participants without cirrhosis

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm B

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 12 weeks in HCV genotype 1- infected participants without cirrhosis

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm C

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD for 8 weeks in HCV genotype 1-infected participants without cirrhosis (never opened - Sponsor decision)

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm D

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 8 weeks in HCV genotype 1-infected participants without cirrhosis (never opened - Sponsor decision)

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm E

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD + ribavirin (RBV) 800 mg QD for 12 weeks in HCV genotype 1-infected participants with compensated cirrhosis (never opened - Sponsor decision)

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm F

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD for 12 weeks in HCV genotype 1- infected participants with compensated cirrhosis

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm G

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD + ribavirin (RBV) 800 mg QD for 12 weeks in HCV genotype 1-infected participants with compensated cirrhosis (never opened - Sponsor decision)

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm H

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 12 weeks in HCV genotype 1-infected participants with compensated cirrhosis (never opened - Sponsor decision)

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm I

Experimental group

Description:

ABT-493 300 mg once daily (QD) + ABT-530 120 mg QD for 12 weeks in HCV genotype 4-, 5-, and 6-infected participants without cirrhosis

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm J

Experimental group

Description:

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 12 weeks in HCV genotype 4-, 5-, and 6-infected participants without cirrhosis (never opened - Sponsor decision)

Treatment:

Drug: ABT-493

Drug: ABT-530

Arm K

Experimental group

Description:

ABT-493 300 mg once daily (QD) + ABT-530 120 mg QD for 8 weeks in HCV genotype 1- infected participants without cirrhosis

Treatment:

Drug: ABT-493

Drug: ABT-530