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
  Purpose

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


Condition Intervention Phase
Chronic Hepatitis C
Hepatitis C (HCV)
Hepatitis C Genotype 1
Drug: ABT-450
Drug: ABT-333
Drug: ABT-267
Drug: Ribavirin
Drug: Ritonavir
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, 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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).



Secondary Outcome Measures:
  • 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).


Enrollment: 580
Study Start Date: October 2011
Study Completion Date: September 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
Drug: ABT-450
ABT-450 tablets
Drug: ABT-333
ABT-333 tablets
Other Name: Dasabuvir
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 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.
Drug: ABT-450
ABT-450 tablets
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 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.
Drug: ABT-450
ABT-450 tablets
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 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.
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: Ritonavir
Ritonavir capsules
Other Name: Norvir
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.
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 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.
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 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.
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 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.
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 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.
Drug: ABT-450
ABT-450 tablets
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 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.
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 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.
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 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.
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 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.
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

Detailed Description:

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.

  Eligibility

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

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
  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: NCT01464827

  Show 97 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Daniel 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: NCT01464827     History of Changes
Other Study ID Numbers: M11-652, 2010-022455-31
Study First Received: September 28, 2011
Results First Received: December 23, 2014
Last Updated: April 2, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
France: Afssaps - Agence francaise de securite sanitaire des produits de sante (Saint-Denis)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Germany: Federal Institute for Drugs and Medical Devices
New Zealand: Medsafe
Czech Republic: State Institute for Drug Control
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Chile: Ministry of Health
Mexico: Ministry of Health
Brazil: National Health Surveillance Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by AbbVie:
Hepatitis C Genotype 1
Hepatitis C
Interferon-Free
HCV
Chronic Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
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 May 21, 2015