A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01685203
First received: September 12, 2012
Last updated: August 3, 2015
Last verified: August 2015
  Purpose

The purpose of this study is to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: ABT-450/r
Drug: ABT-267
Drug: Ribavirin (RBV)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment [ Time Frame: 12 weeks after the last actual 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.


Secondary Outcome Measures:
  • Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment [ Time Frame: 24 weeks after the last actual 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]) 24 weeks after the last dose of study drug.

  • Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. [ Time Frame: Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8 ] [ 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 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).

  • Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. [ Time Frame: Within 12 weeks after the last dose of study drug ] [ Designated as safety issue: No ]
    Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment.

  • Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events [ Time Frame: Adverse events were collected from the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8. ] [ Designated as safety issue: Yes ]
    Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug.


Enrollment: 316
Study Start Date: August 2012
Study Completion Date: February 2015
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Experimental: Group 2
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Experimental: Group 3
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Experimental: Group 4
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4 -infected participants
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Drug: Ribavirin (RBV)
Tablet
Experimental: Group 5
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Experimental: Group 6
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Drug: Ribavirin (RBV)
Tablet
Experimental: Group 7
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir
Experimental: Group 8
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis
Drug: ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
Other Name: ABT-450 also known as paritaprevir
Drug: ABT-267
Tablet
Other Name: ABT-267 also known as ombitasvir

Detailed Description:

This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Safety and efficacy data through 18 June 2014 are included in this interim analysis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other study groups completed the treatment period and completed through Week 12 of the post-treatment period. Groups 2 and 3 completed the study (through post-treatment Week 48), Groups 1 and 4 completed through post-treatment Week 24, and Groups 6, 7, and 8 completed through post-treatment week 12.

  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 postmenopausal for more than 2 years or surgically sterile
  • Subjects must meet one of the following:

    • Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR
    • Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV);
  • Body mass index (BMI) is ≥ 18 to < 38 kg/m^2.
  • Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening.
  • 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 were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV.
  • Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
  • Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.
  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: NCT01685203

Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Nilou Mobashery, 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: NCT01685203     History of Changes
Other Study ID Numbers: M13-393, 2011-005762-38
Study First Received: September 12, 2012
Results First Received: June 9, 2015
Last Updated: August 3, 2015
Health Authority: Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Turkey: Ministry of Health
United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by AbbVie:
Hepatitis C Virus
Ribavirin-Free
Hepatitis C Genotype 1
Hepatitis C
Interferon-Free
Chronic Hepatitis C
Compensated cirrhosis
Hepatitis C Genotype 4
Paritaprevir
Ombitasvir
Ritonavir
Ribavirin

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

ClinicalTrials.gov processed this record on August 27, 2015