Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01563536
First received: January 27, 2012
Last updated: July 8, 2013
Last verified: July 2013

January 27, 2012
July 8, 2013
February 2012
April 2012   (final data collection date for primary outcome measure)
  • Analysis of pharmacokinetic variables [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Assess plasma concentrations of each drug and possible metabolites
  • Safety of all treatment regimens [ Time Frame: Baseline to end of treatment (up to 12 weeks) ] [ Designated as safety issue: Yes ]
    Analysis of safety measures including but not limited to tabulation of adverse events, physical exam, vital signs, ECGs and clinical lab results (including chemistry, hematology and urine).
  • Percentage of subjects achieving 24-week sustained virologic response (SVR24) following treatment with 3 DAAs and RBV in HCV genotype 1-infected treatment-naïve adults [ Time Frame: 24 weeks after last dose of study drug ] [ Designated as safety issue: No ]
    Assess the percentage of subjects achieving SVR24 (HCV RNA (Ribonucleic acid) < lower limit of quantitation (LLOQ) 24 weeks after last dose of study drug
  • Development and persistence of resistance to DAA therapy [ Time Frame: 48 weeks after last dose of study drug ] [ Designated as safety issue: No ]
    Assesses the fold change from baseline and reference HCV samples in the half maximal effective concentration at various time points, and identify mutations at each amino acid position by population and/or clonal nucleotide sequencing compared to baseline and prototypic sequences and assess the development and persistence of viral resistance with various treatment regimens.
  • Number of subject with adverse events as a measure of safety and tolerability [ Time Frame: Baseline to day 3 ] [ Designated as safety issue: Yes ]
    Incidence of SAEs, discontinuations and lab abnormalities
  • Change in HCV RNA levels during ABT-267 during monotherapy treatment [ Time Frame: Baseline to day 3 ] [ Designated as safety issue: No ]
    Maximum decrease in HCV RNA levels from baseline
Complete list of historical versions of study NCT01563536 on ClinicalTrials.gov Archive Site
  • Percentage of subjects with rapid virologic response (RVR) [HCV RNA < lower limit of quantitation (LLOQ) at CT Week 4] [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Assess the percentage of subjects with HCV RNA < LLOQ 4 weeks after beginning therapy with 3 DAAs and RBV
  • Percentage of subjects with continued early virologic response (cEVR) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Assess the percentage of subjects with HCV RNA < LLOQ 12 weeks after beginning therapy with 3 DAAs and RBV
  • Percentage of subjects with sustained virologic response 12 weeks post-dosing (SVR12actual) and the percentage of subjects with sustained virologic response 24 weeks post-dosing (SVR24actual) [ Time Frame: 24 and 36 weeks, respectively ] [ Designated as safety issue: No ]
    Assess the percentage of subjects with HCV RNA < LLOQ 12 weeks after the last dose of study drug and the percentage of subjects with HCV RNA < LLOQ 24 weeks after the last dose of study drug
  • Percentage of subjects with extended rapid virologic response (eRVR) [ Time Frame: Week 4 through week 12 ] [ Designated as safety issue: No ]
    Assess the percentage of subjects with HCV RNA < LLOQ at combination therapy Study Week 4 through combination therapy Study Week 12
  • Exploration of the exposure-response relationship between ABT-267 concentrations and antiviral efficacy [ Time Frame: 24 weeks after last dose of ABT- 267 ] [ Designated as safety issue: No ]
    Assess the percentage of subjects with HCV RNA < LLOQ 24 weeks after last dose of ABT-267 in each treatment arm
  • Number of subject with adverse events as a measure of safety and tolerability [ Time Frame: 60 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with sustained virologic response (SVR) [ Time Frame: Through 24 weeks post treatment ] [ Designated as safety issue: No ]
    SVR (HCV RNA <LLOQ) measured at post treatment week 12 and week 24
  • Percentage of subjects with Rapid Virologic Response (RVR) [ Time Frame: Through week 4 ] [ Designated as safety issue: No ]
    HCV RNA < LLOQ at week 4
  • Percentage of subjects with extended Early Virologic Response (eEVR) [ Time Frame: Through week 12 ] [ Designated as safety issue: No ]
    HCV RNA <LLOQ from week 4 through week 12
  • Percentage of subject with complete Early Virologic Response (cEVR) [ Time Frame: Through week 12 ] [ Designated as safety issue: No ]
    HCV RNA <LLOQ at week 12
Not Provided
Not Provided
 
Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
An Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects

Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 and the combination of other direct-acting antiviral agents (DAA) and ribavirin (RBV) in subjects with chronic Hepatitis C virus (HCV) infection.

A study to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of ABT-267 as 2-day monotherapy in subjects with chronic HCV infection. The study will also evaluate the safety and effect of experimental drugs ABT-267, ABT-450, ritonavir (ABT-450/r), ABT-333, and ribavirin (RBV) in subjects with chronic HCV infection. The study will test the safety and effects of combinations of these drugs in treatments up to 12 weeks.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HCV Infection
  • Drug: ABT-267
    ABT-267 (tablets)
  • Drug: ABT-450/r
    ABT-450 (tablets) dosed with ritonavir (capsules)
  • Drug: ABT-333
    ABT-333 (tablets)
  • Drug: Ribavirin (RBV)
    Ribavirin (tablets)
  • Experimental: Arm 1
    ABT-267 Dose 1, 2 days Monotherapy followed by ABT-267 Dose 1 in combination with ABT-450/r, ABT-333, and ribavirin
    Interventions:
    • Drug: ABT-267
    • Drug: ABT-450/r
    • Drug: ABT-333
    • Drug: Ribavirin (RBV)
  • Experimental: Arm 2
    ABT-267 Dose 2, 2 days Monotherapy followed by ABT-267 Dose 2 in combination with ABT-450/r, ABT-333, and ribavirin
    Interventions:
    • Drug: ABT-267
    • Drug: ABT-450/r
    • Drug: ABT-333
    • Drug: Ribavirin (RBV)
  • Experimental: Arm 3
    ABT-267 Dose 3, 2 days Monotherapy followed by ABT-267 Dose 3 in combination with ABT-450/r, ABT-333, and ribavirin
    Interventions:
    • Drug: ABT-267
    • Drug: ABT-450/r
    • Drug: ABT-333
    • Drug: Ribavirin (RBV)
  • Experimental: Arm 4
    ABT-267 Dose 4, 2 days Monotherapy followed by ABT-267 Dose 4 in combination with ABT-450/r, ABT-333, and ribavirin
    Interventions:
    • Drug: ABT-267
    • Drug: ABT-450/r
    • Drug: ABT-333
    • Drug: Ribavirin (RBV)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
June 2013
April 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
  • Subject has never received antiviral treatment for hepatitis C infection.
  • 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).
  • Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment.
  • Subject has plasma HCV RNA level > 10,000 IU/mL at Screening

Exclusion Criteria:

  • History of severe, life-threatening or other significant sensitivity to any drug.
  • Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant.
  • Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
  • Positive test result for hepatitis B surface antigen or anti-HIV antibodies.
  • Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/APRI or FibroScan® showing cirrhosis or extensive bridging fibrosis.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01563536
M13-386
No
AbbVie ( AbbVie (prior sponsor, Abbott) )
AbbVie (prior sponsor, Abbott)
Not Provided
Study Director: Andrew L Campbell, MD AbbVie
AbbVie
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP