A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 with Ritonavir (ABT-450/r) and ABT-267 in Adults with Chronic Hepatitis C Virus Infectio

Conditions: Chronic Hepatitis C Infection
MedDRA version: 16.0Level: PTClassification code 10008909Term: Chronic hepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2011-005762-38-HU

Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 320

Inclusion Criteria

1.Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
2.Subjects must meet one of the following categories:
• Treatment-naïve: Subject has never received antiviral treatment for hepatitis C infection (Subjects with HCV genotype 1b infection with or without cirrhosis or HCV genotype 4 infection; Groups 1, 2, 4, and 7); OR•Prior null responders: Subject has documentation that they previously received pegIFN/RBV for at least 10 weeks and failed to achieve a 2 log10 IU/mL HCV RNA decrease at Week 12 (Week 10 to Week 16) (Subjects with HCV genotype 1b infection with or without cirrhosis or HCV genotype 4 infection; Groups 3, 5, 6, and 8); OR•Partial responder: Received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved = 2 log10 reduction in HCV RNA at Week 12 (Weeks 10 – 16), but failed to achieve HCV RNA undetectable at the end of treatment (Subjects with HCV genotype 1b infection and compensated cirrhosis or HCV genotype 4 infection; Group 5, 6, and 8); OR•Relapser: Received at least 36 weeks of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 52 weeks of treatment follow-up (Subjects with HCV genotype 1b infection and compensated cirrhosis or HCV genotype 4 infection; Group 5, 6, and 8).
3.Body mass index (BMI) is = 18 to < 38 kg/m2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
4.Chronic HCV genotype 1b or 4-infection for at least 6 months prior to study screening.
5.Subject has plasma HCV RNA level > 10,000 IU/mL at Screening.

Main Inclusion for Substudy 1:
1. Per local standard practice, documented results of:
- Liver biopsy within 24 months prior to screening or during screening demonstrating the absence of cirrhosis.
- Only in the absence of a biopsy within the 24 months prior to screening or during screening:
- a screening FibroTest score of = 0.72 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) = 2; or
- a screening FibroScan® result of < 9.6 kPa. Subjects with a non qualifying FibroTest/APRI or FibroScan result may only be enrolled if they have a qualifying liver biopsy performed during screening.

Main Inclusion for Substudy 2:
1. Per local standard practice, documentation of cirrhosis by one of the following methods:
- Previous histologic diagnosis on liver biopsy, e.g., Metavir Score of > 3 (including 3/4 or 3 – 4), Ishak score of > 4 or,
- FibroScan score = 14.6 kPa within 6 months of Screening or during the Screening Period (FibroScan must be locally approved to qualify for entrance criteria). Subjects with a non-qualifying FibroScan result may only be enrolled if they have a qualifying liver biopsy performed during screening.
2. Compensated cirrhosis defined as Child-Pugh score of = 6 at Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.History of severe, life-threatening or other significant sensitivity to any drug.
2.Females who are pregnant or breastfeeding.
3.Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
4.Positive test result for hepatitis B surface antigen or anti-HIV antibodies.
5.Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis.

Main Exclusion for Substudy 1:
1. Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis.
2. Absolute neutrophil count (ANC) < 1500 cells/µL (< 1200 cells/µL for subjects of black/African descent)

Main Exclusion for Substudy 2:
1. Any current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation such as ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to assess the safety and efficacy (the percentage of subjects with HCV RNA <LLOG 12 weeks after the last actual dose of study drug (SVR12 actual)) of ABT-450/r and ABT-267 among HCV subjects as specified in the Substudies 1 and 2 objectives below. ;Secondary Objective: To assess the rates of SVR24 actual (HCV RNA <LL0Q 24 weeks after the last actual dose of study drug), on-treatment virologic failure, and post-treatment relapse among all treated subjects.;Primary end point(s): The primary efficacy endpoint is the percentage of subjects with SVR12 actual (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug)in each treatment group. The primary comparison will be between Groups 2 and 3. Additional comparisons between Groups 1 and 4 and between Groups 5 and 6 (if both are enrolled) will be performed. ;Timepoint(s) of evaluation of this end point: 12 weeks after last dose of study drug

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): ? The percentage of subjects with SVR24 actual (HCV RNA < LLOQ 24 weeks after the last actual dose of study drug), <br>? The percentage of subjects with on-treatment virologic failure<br>? The percentage of subjects with post-treatment relapse;Timepoint(s) of evaluation of this end point: 24 weeks after last dose of study drug.

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