ABT-450 With Ritonavir and ABT-267 and/or ABT-333 With and Without Ribavirin in Genotype 1 Hepatitis C Virus Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01464827
First received: September 28, 2011
Last updated: April 2, 2015
Last verified: April 2015

September 28, 2011
April 2, 2015
October 2011
March 2013   (final data collection date for primary outcome measure)
  • Number of Participants With Adverse Events (AEs) [ Time Frame: From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks). ] [ Designated as safety issue: Yes ]

    An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment.

    The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs) and to ribavirin, and rated the severity of each event as either:

    Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening.

    A serious adverse event was any event that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.

  • Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin [ Time Frame: Post Treatment Week 24 ] [ Designated as safety issue: No ]

    The percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (SVR24), defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantitation (LLOQ), without any confirmed quantifiable (≥ LLOQ) post-treatment value before that time point. HCV RNA levels were measured from plasma by a central laboratory. The LLOQ for the assay was 25 IU/mL.

    The primary efficacy endpoint was the comparison between treatment-naïve participants following 8 weeks of treatment with 3 DAAs and ribavirin and those with 12 weeks of treatment with 3 DAAs and ribavirin (Group A versus Group G).

  • Safety of all treatment regimens [ Time Frame: Baseline to End of Active Treatment (up to 24 weeks) ] [ Designated as safety issue: Yes ]
    Assess the safety of all treatment regimens
  • Percentage of subjects achieving 24-week sustained virologic response (SVR24) following treatment with different durations of 3 DAAs (direct acting anti-virals) and RBV (ribavirin) in HCV (HepatitisC) genotype 1-infected treatment-naïve adults [ Time Frame: Post Treatment Week 24 ] [ Designated as safety issue: No ]
    Assess the percentage of subjects achieving SVR24 (HCV RNA < LLOD (lower limit of detection) at post-treatment Week 24) following treatment with different durations of 3 DAAs (ABT-450/r, ABT-267, and ABT-333) and RBV in HCV genotype 1-infected treatment-naïve adults
Complete list of historical versions of study NCT01464827 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs (ABT-450/ritonavir, ABT-267, and ABT-333) and ribavirin in both treatment naïve and null-responder participants for 8 weeks (Group A) versus 12 weeks (Groups F + G + K + L) versus 24 weeks (Groups H + I + M + N).
  • Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 2 DAAs (ABT-450/ritonavir plus ABT-333 [Group B] or ABT-450/ritonavir plus ABT-267 [Groups C + D + J]) and ribavirin versus 3 DAAs (ABT-450/ritonavir plus ABT-333 and ABT-267) and ribavirin (Groups F + G + K + L).
  • Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs with or without ribavirin (Group E versus Groups F + G + K + L).
  • Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs and ribavirin in participants who were treatment-naïve versus those who were null-responders to previous HCV therapy (Groups F + G + H + I versus Groups K + L + M + N).
  • Percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment of different durations with 3 DAAs with RBV in treatment naïve and null responder subjects [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: Yes ]
    Compare the percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment of different durations with 3 DAAs (ABT-450/r, ABT-267, and ABT-333) with RBV in treatment naïve and null responder subjects
  • Percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment with 3 DAAs with RBV versus 3 DAAs without RBV in treatment naïve subjects [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    Compare the percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment with 3 DAAs (ABT-450/r, ABT-267, and ABT-333) with RBV versus 3 DAAs without RBV in treatment naïve subjects
  • Percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment with 2 DAAs with RBV versus 3 DAAs with RBV in treatment naïve and null responder subjects [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    Compare the percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment with 2 DAAs (ABT-450/r and ABT-333) with RBV versus 3 DAAs (ABT-450/r, ABT-267, and ABT-333) with RBV in treatment naïve subjects and null responder subjects
  • Percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment with 3 DAAs with RBV in with different doses of ABT-450/r in treatment treatment naïve and null responder subjects [ Time Frame: Post-Treatment Week 24 ] [ Designated as safety issue: No ]
    Compare the percentage of subjects achieving SVR24 (HCV RNA < LLOD at post-treatment Week 24) following treatment with 3 DAAs with different doses of ABT-450/r with RBV in treatment treatment naïve and null responder subjects
  • Any emerged or enriched mutations Post-Baseline by mixed population and/or clonal sequencing [ Time Frame: Day 1 to Post-Treatment Week 48 or Premature Discontinuation ] [ Designated as safety issue: No ]
    To examine any emerged or enriched mutations Post-Baseline by mixed population and/or clonal sequencing
Not Provided
Not Provided
 
ABT-450 With Ritonavir and ABT-267 and/or ABT-333 With and Without Ribavirin in Genotype 1 Hepatitis C Virus Infected Patients
A Randomized, Open-Label, Multicenter Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics, of ABT-450 With Ritonavir (ABT-450/r) in Combination With ABT-267 and/or ABT-333 With and Without Ribavirin (RBV) for 8, 12 or 24 Weeks in Treatment-Naïve and Null Responder Subjects With Genotype 1 Chronic Hepatitis C Virus Infection

This is a study of combination direct-acting antiviral agents (DAA) with or without ribavirin (RBV) in patients with chronic Hepatitis C Virus (HCV).

A study to evaluate the safety and effectiveness of experimental drugs ABT-450, ABT-267 (also known as ombitasvir), ABT-333 (also known as dasabuvir), ritonavir, and ribavirin in participants with HCV. The study will test the safety and effects of combinations of these drugs in treatments up to 24 weeks.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Hepatitis C
  • Hepatitis C (HCV)
  • Hepatitis C Genotype 1
  • Drug: ABT-450
    ABT-450 tablets
  • Drug: ABT-333
    ABT-333 tablets
    Other Name: Dasabuvir
  • Drug: ABT-267
    ABT-267 tablets
    Other Name: Ombitasvir
  • Drug: Ribavirin
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).
  • Drug: Ritonavir
    Ritonavir capsules
    Other Name: Norvir
  • Experimental: Group A
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group B
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group C
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group D
    Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group E
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ritonavir
  • Experimental: Group F
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group G
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group H
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group I
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group J
    Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group K
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group L
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group M
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
  • Experimental: Group N
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Interventions:
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: ABT-267
    • Drug: Ribavirin
    • Drug: Ritonavir
Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, Everson GT, Kwo P, Foster GR, Sulkowski MS, Xie W, Pilot-Matias T, Liossis G, Larsen L, Khatri A, Podsadecki T, Bernstein B. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014 Jan 16;370(3):222-32. doi: 10.1056/NEJMoa1306227.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
580
September 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males and females 18-70 years old, inclusive
  • Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control
  • Chronic hepatitis C virus (HCV), genotype 1 infection
  • Treatment-naive OR null-responders to previous treatment with pegylated interferon (pegIFN) and ribavirin (at least 12 weeks of treatment and failure to achieve a 2 log10 HCV RNA decrease at Week 12)
  • No evidence of liver cirrhosis

Exclusion Criteria:

  • Significant liver disease with any cause other than HCV as the primary cause
  • Positive hepatitis B surface antigen and anti-human immunodeficiency virus antibody
  • Positive screen for drugs and alcohol
  • Significant sensitivity to any drug
  • Use of contraindicated or prohibited medications within 1 month of dosing
  • Abnormal laboratory tests
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   France,   Germany,   New Zealand,   Puerto Rico,   Spain,   United Kingdom
Chile
 
NCT01464827
M11-652, 2010-022455-31
Yes
AbbVie ( AbbVie (prior sponsor, Abbott) )
AbbVie (prior sponsor, Abbott)
Not Provided
Study Director: Daniel Cohen, MD AbbVie
AbbVie
April 2015

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