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
  Purpose

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.


Condition Intervention Phase
HCV Infection
Drug: ABT-267
Drug: ABT-450/r
Drug: ABT-333
Drug: Ribavirin (RBV)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 12
Study Start Date: February 2012
Study Completion Date: June 2013
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 2
ABT-267 Dose 2, 2 days Monotherapy followed by ABT-267 Dose 2 in combination with ABT-450/r, ABT-333, and ribavirin
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 3
ABT-267 Dose 3, 2 days Monotherapy followed by ABT-267 Dose 3 in combination with ABT-450/r, ABT-333, and ribavirin
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 4
ABT-267 Dose 4, 2 days Monotherapy followed by ABT-267 Dose 4 in combination with ABT-450/r, ABT-333, and ribavirin
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)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01563536

Locations
United States, California
Site Reference ID/Investigator# 68002
Bakersfield, California, United States, 93301
United States, Florida
Site Reference ID/Investigator# 67383
Orlando, Florida, United States, 32809
United States, Maryland
Site Reference ID/Investigator# 67382
Annapolis, Maryland, United States, 21401
United States, New York
Site Reference ID/Investigator# 67385
Poughkeepsie, New York, United States, 12601
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Andrew L Campbell, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01563536     History of Changes
Other Study ID Numbers: M13-386
Study First Received: January 27, 2012
Last Updated: July 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Hepatitis C
Genotype 1

Additional relevant MeSH terms:
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014