A Study to Evaluate Paritaprevir With Ritonavir (ABT-450/r) When Given Together With Ombitasvir and With and Without Ribavirin (RBV) in Treatment-Naïve Participants With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV) (Navigator)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01458535
First received: September 23, 2011
Last updated: May 31, 2016
Last verified: May 2016
  Purpose
The purpose of this study was to evaluate the efficacy, safety and pharmacokinetics of ABT-450/r when given together with ABT-267 and with and without RBV in treatment-naïve participants with genotype 1, 2 or 3 chronic HCV infection.

Condition Intervention Phase
Hepatitis C Virus
Drug: ABT-450
Drug: ABT-267
Drug: ribavirin
Drug: ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Sequential Arm, Multicenter Study to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-267 With and Without Ribavirin (RBV) in Treatment-Naïve Subjects With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV) Infection

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 [(Extended Rapid Virologic Response (eRVR)] [ Time Frame: Week 4 through Week 12 ] [ Designated as safety issue: No ]
    Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL). Participants with missing data were imputed as failures.


Secondary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment [ Time Frame: Post-treatment Day 1 to Post-treatment Week 12 ] [ Designated as safety issue: No ]
    Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug. Participants with missing data were imputed as failures.

  • Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment [ Time Frame: Post-treatment Day 1 to Post-treatment Week 24 ] [ Designated as safety issue: No ]
    Sustained Virologic Response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; < 25 IU/mL) 24 weeks after the last dose of study drug. Participants with missing data were imputed as failures.

  • Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL) [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2. Participants with missing data were imputed as failures.

  • Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) at Week 4 Rapid Virologic Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL). Participants with missing data were imputed as failures.

  • Percentage of Participants With Virologic Failure During Treatment [ Time Frame: Day 1 through Week 12 ] [ Designated as safety issue: No ]
    Virologic failure during treatment is defined as a participant meeting any virologic stopping criteria, including 1) rebound (defined as the first day of 2 consecutive increases of at least 0.5 log10 IU/mL above nadir (local minimum value), or first day of 2 consecutive HCV RNA >= LLOQ for participants who previously achieved HCV RNA < LLOQ) during treatment, 2) participant who fails to suppress (defined as never achieving HCV RNA < LLOQ during treatment).

  • Percentage of Participants Who Experienced Virologic Relapse Through End of Post Treatment Period (up to 48 Weeks) [ Time Frame: Post-treatment Day 1 to Post-treatment Week 48 ] [ Designated as safety issue: No ]
    Virologic relapse is defined as confirmed hepatitis C virus (HCV) ribonucleic acid (RNA) >= lower limit of quantitation (LLOQ) (2 consecutive measurements >= LLOQ) at any point in the post-treatment period among participants with HCV RNA < LLOQ at the end of treatment. Participants with missing data were imputed as failures.


Enrollment: 61
Study Start Date: September 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABT-450/r and ABT-267 plus RBV in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection.
Drug: ABT-450
tablets
Other Name: paritaprevir
Drug: ABT-267
tablets
Other Name: ombitasvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Name: Norvir
Experimental: ABT-450/r and ABT-267 plus RBV in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection.
Drug: ABT-450
tablets
Other Name: paritaprevir
Drug: ABT-267
tablets
Other Name: ombitasvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Name: Norvir
Experimental: ABT-450/r and ABT-267 plus RBV in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection.
Drug: ABT-450
tablets
Other Name: paritaprevir
Drug: ABT-267
tablets
Other Name: ombitasvir
Drug: ribavirin
tablets
Drug: ritonavir
capsules
Other Name: Norvir
Experimental: ABT-450/r and ABT-267 in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection.
Drug: ABT-450
tablets
Other Name: paritaprevir
Drug: ABT-267
tablets
Other Name: ombitasvir
Drug: ritonavir
capsules
Other Name: Norvir
Experimental: ABT-450/r and ABT-267 in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection.
Drug: ABT-450
tablets
Other Name: paritaprevir
Drug: ABT-267
tablets
Other Name: ombitasvir
Drug: ritonavir
capsules
Other Name: Norvir
Experimental: ABT-450/r and ABT-267 in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection.
Drug: ABT-450
tablets
Other Name: paritaprevir
Drug: ABT-267
tablets
Other Name: ombitasvir
Drug: ritonavir
capsules
Other Name: Norvir

Detailed Description:
This was a 2 sequential arm, combination treatment study where each arm contained 3 cohorts: one each for HCV genotype 1, 2, and 3. The study consisted of 2 phases, a treatment phase and a post-treatment phase. The treatment phase was designed to explore the antiviral activity, safety and pharmacokinetics of ABT-450/r dosed in combination with ABT-267 with and without RBV for up to 12 weeks. The post-treatment phase was designed to monitor and evaluate Sustained Virologic Response (SVR) 12, SVR 24, and the evolution and persistence of viral resistance to ABT-267 and ABT-450 in HCV genotype 1-, 2-, and 3-infected participants who have been exposed to ABT-267 and ABT-450/r. Arms 1 and 2 were enrolled sequentially.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants who had a body mass index 18 to < 35 kg/m^2.
  • Females were either postmenopausal for at least 2 years, surgically sterile, or willing to use at least 2 effective forms of birth control.
  • Males must have been surgically sterile or agreed to use at least 2 effective forms of birth control throughout the course of the study.
  • Participants were in a condition of general good health, other than the HCV infection.
  • Participants had a chronic HCV genotype 1, 2, or 3 infection for at least 6 months, a plasma HCV RNA > 50,000 IU/mL, and FibroTest score <= 0.72 and aspartate aminotransferase (AST) to platelet ratio index <= 2, Fibroscan® result of < 9.6 kilopascal (kPa), or absence of cirrhosis based on a liver biopsy.

Exclusion Criteria:

  • Positive drug screen
  • Previous use of anti-HCV agents
  • History of cardiac disease
  • History of uncontrolled diabetes or diabetes requiring insulin
  • Abnormal laboratory results
  • Females who were pregnant or planned to become pregnant within 6 months after their last dose of study drug/RBV or were breastfeeding; males whose partners were pregnant or would become pregnant within 6 months after their last dose of study drug/RBV
  • Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus (HIV) antibody (Ab). Negative HIV status was to be confirmed at screening.
  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: NCT01458535

Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Andrew Campbell, MD AbbVie
  More Information

Additional Information:
Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01458535     History of Changes
Other Study ID Numbers: M12-998 
Study First Received: September 23, 2011
Results First Received: May 31, 2016
Last Updated: May 31, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Genotype 1
Genotype 2
Genotype 3
Hepatitis C Virus
ABT-450/r
Ribavirin
ABT-267
Ombitasvir
Paritaprevir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ritonavir
Ribavirin
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimetabolites

ClinicalTrials.gov processed this record on August 24, 2016