A Study to Evaluate Chronic Hepatitis C Infection in Adults With Genotype 1b Infection (PEARL-III)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01767116
First received: November 30, 2012
Last updated: August 19, 2015
Last verified: August 2015
  Purpose

The purpose of this study is to evaluate the safety and antiviral activity of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) with and without ribavirin (RBV) in patients with chronic hepatitis C virus genotype 1b (HCV GT1b) infection without cirrhosis.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: ABT-450/r/ABT-267, ABT-333
Drug: Ribavirin
Drug: Placebo for ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of the Combination of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With and Without Ribavirin (RBV) in Treatment-Naive Adults With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL-III)

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate [ Time Frame: 12 weeks after last dose of study drug ] [ Designated as safety issue: No ]

    The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.

    The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN).



Secondary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV [ Time Frame: 12 weeks after last dose of study drug ] [ Designated as safety issue: No ]

    The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.

    The secondary endpoint was the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV.


  • Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment [ Time Frame: Baseline (Day 1) and Week 12 (End of Treatment) ] [ Designated as safety issue: Yes ]
    The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment.

  • Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate [ Time Frame: 12 weeks after last dose of study drug ] [ Designated as safety issue: No ]

    The percentage of participants with sustained virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.

    The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV.


  • Percentage of Participants With Virologic Failure During Treatment [ Time Frame: Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).

  • Percentage of Participants With Virologic Relapse After Treatment [ Time Frame: Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-treatment) ] [ Designated as safety issue: No ]
    Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period.


Enrollment: 419
Study Start Date: December 2012
Study Completion Date: August 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABT-450/r/ABT-267 and ABT-333, Plus RBV
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Drug: ABT-450/r/ABT-267, ABT-333
Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
Other Names:
  • ABT-267 also known as ombitasvir
  • ABT-450 also known as paritaprevir
  • ABT-333 also known as dasabuvir
  • Viekira PAK
Drug: Ribavirin
Capsule
Experimental: ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks
Drug: ABT-450/r/ABT-267, ABT-333
Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
Other Names:
  • ABT-267 also known as ombitasvir
  • ABT-450 also known as paritaprevir
  • ABT-333 also known as dasabuvir
  • Viekira PAK
Drug: Placebo for ribavirin
Capsule

Detailed Description:

A randomized, double-blind, multicenter study to evaluate the safety and antiviral activity of the combination of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 with and without ribavirin (RBV) in treatment-naïve, noncirrhotic participants with chronic hepatitis C virus genotype 1b (HCV GT1b) infection.

  Eligibility

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

Inclusion Criteria:

  • Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile
  • Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening)
  • Subject has never received antiviral treatment for hepatitis C infection
  • 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 or anti-human immunodeficiency virus antibody
  • Positive screen for drugs or alcohol
  • Significant sensitivity to any drug
  • Use of contraindicated medications within 2 weeks of dosing
  • Abnormal laboratory tests
  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: NCT01767116

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

Additional Information:
No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01767116     History of Changes
Other Study ID Numbers: M13-961, 2012-003687-52
Study First Received: November 30, 2012
Results First Received: December 23, 2014
Last Updated: August 19, 2015
Health Authority: United States: Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Austria: Federal Office for Safety in Health Care
Israel: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Russia: Ethics Committee
Portugal: Ethics Committee for Clinical Research
Hungary: Scientific and Medical Research Council Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Poland: Ethics Committee
Spain: Comité Ético de Investigación Clínica
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Portugal: National Pharmacy and Medicines Institute
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Romania: Ethics Committee
Israel: Ethics Commission
Austria: Agency for Health and Food Safety
Belgium: Ethics Committee
Romania: National Agency for Medicines and Medical Devices

Keywords provided by AbbVie:
Interferon-Free
Hepatitis C Genotype 1b
Chronic Hepatitis C
Hepatitis C Virus
Hepatitis C
Treatment-Naive
Paritaprevir
Ombitasvir
Dasabuvir
Viekira PAK
Ribavirin

Additional relevant MeSH terms:
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Infection
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015