A Study of Induction Dosing With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C (CHC) Genotype 1 Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00192647
First received: September 13, 2005
Last updated: May 6, 2016
Last verified: May 2016
  Purpose
This study will evaluate the addition of a higher-dose induction treatment period with peginterferon (PEG-IFN) alfa-2a (Pegasys) and ribavirin prior to standard-dose treatment with PEG-IFN alfa-2a and ribavirin, compared to standard-dose treatment, in treatment-naive participants with CHC, genotype 1 infection.

Condition Intervention Phase
Hepatitis C, Chronic
Drug: PEG-IFN alfa-2a
Drug: Ribavirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV, Randomised, Multicentre, Efficacy and Safety Study Examining the Effect of Induction Dosing With the Combination of Peginterferon Alfa-2a and Ribavirin in Patients With Chronic Hepatitis C Infected With Hepatitis C Genotype 1

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virological Response According to Scheduled Treatment Period [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Sustained virological response was calculated as the percentage of participants with undetectable (less than [<] 15 international units per milliliter [IU/mL]) hepatitis C virus (HCV) ribonucleic acid (RNA) as measured by the Roche TaqMan HCV Test 24 weeks after completion of the scheduled 48-week treatment period.


Secondary Outcome Measures:
  • Percentage of Participants With End-of-Treatment Virological Response According to Scheduled Treatment Period [ Time Frame: Weeks 48 ] [ Designated as safety issue: No ]
    Virological response at the end of the scheduled treatment period was defined as the percentage of participants with undetectable (<15 IU/mL) HCV RNA as measured by the Roche TaqMan HCV Test at Week 48.

  • Percentage of Participants With Virological Responses Over Time [ Time Frame: Weeks 4, 8, 12, and 24 ] [ Designated as safety issue: No ]
    Virological response was defined as undetectable HCV RNA (<15 IU/mL) as measured by the Roche TaqMan HCV Test. Participants without HCV RNA measurements at a study week are considered non responders at that study week.

  • Percentage of Participants With Relapse of End-of-treatment Virological Response [ Time Frame: Actual end of treatment (Week 48) up to last follow up (maximum up to Week 72) ] [ Designated as safety issue: No ]
    Relapse was determined based on virological response at the actual end of treatment and was calculated by dividing the number of participants who achieved a virological response at end of treatment but later had detectable HCV RNA at the last assessment post-treatment by the number of participants with a virological response at end of treatment, defined as undetectable HCV RNA (<15 IU/mL). Participants who achieved a virological response at end of treatment but did not have any HCV RNA assessment during follow-up were excluded and were not considered as having relapsed. However, if no assessment was available within the end of-treatment time window but the participant had a sustained virological response according to the actual treatment period, backward imputation was used and the participant was considered to have achieved an end-of-treatment virological response in the analysis.

  • Percentage of Participants With Predictive Values of Virological Response for Sustained Virological Response [ Time Frame: Weeks 4, 12 ] [ Designated as safety issue: No ]
    The ability of virological responses to predict sustained virological response according to the scheduled treatment periods was assessed in terms of positive predictive value (PPV) and negative predictive value (NPV). The PPV indicates probability of achievement of viral suppression (undetectable HCV RNA) for achieving a sustained virological response and the NPV indicates probability of not achieving viral suppression for not achieving a sustained virological response. The PPV at Week 4 or 12 was calculated as the number of participants who achieved viral suppression both at Week 4 or 12 and at Week 72 divided by the number of participants who achieved viral suppression at Week 4 or 12, multiplied by 100. The NPV at Week 4 or 12 was calculated as the number of participants who failed to achieve viral suppression at Week 4 or 12 and at Week 72 divided by the number of participants who failed to achieve viral suppression at Week 4 or 12, multiplied by 100.

  • Change From Baseline in Log10 HCV RNA Values [ Time Frame: Baseline, Weeks 4, 8, 12, 24, and at end of treatment (EoT) (maximum up to Week 48) ] [ Designated as safety issue: No ]
    The mean decrease in log10 HCV RNA levels from baseline was assessed in both the induction group and the standard group.


Enrollment: 896
Study Start Date: August 2004
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PEG-IFN alfa-2a+Ribavirin - Induction Treatment
Participants will receive 12 weeks of induction therapy with PEG-IFN alfa-2a (Pegasys), 360 micrograms (mcg) subcutaneous (SC) once weekly, along with ribavirin, 1000 or 1200 milligrams (mg) orally daily in divided doses. Thereafter, the dose of PEG-IFN alfa-2a will be reduced to 180 mcg SC once weekly and the ribavirin dose maintained for the remaining 36 weeks of treatment.
Drug: PEG-IFN alfa-2a
PEG-IFN alfa-2a will be administered once weekly for 48 weeks, at doses specified in respective arms.
Other Name: Pegasys
Drug: Ribavirin
Ribavirin 1000 or 1200 mg orally daily in divided doses, with the dose determined based on body weight, for 48 weeks.
Other Name: Copegus
Experimental: PEG-IFN alfa-2a+Ribavirin - Standard Treatment
Participants will receive 48 weeks of standard therapy with PEG-IFN alfa-2a, 180 mcg SC once weekly, along with ribavirin, 1000 or 1200 mg orally daily in divided doses.
Drug: PEG-IFN alfa-2a
PEG-IFN alfa-2a will be administered once weekly for 48 weeks, at doses specified in respective arms.
Other Name: Pegasys
Drug: Ribavirin
Ribavirin 1000 or 1200 mg orally daily in divided doses, with the dose determined based on body weight, for 48 weeks.
Other Name: Copegus

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic CHC, genotype 1
  • Chronic liver disease consistent with CHC on a biopsy sample obtained within the previous 36 months as judged by a local pathologist (all countries except Australia)
  • Infection with Hepatitis C virus (Australian sites only had to meet Section 100 criteria for treatment with PEG-IFN alfa-2a plus ribavirin)
  • Compensated liver disease
  • Naive to interferon-based therapy for CHC infection

Exclusion Criteria:

  • Systemic antiviral, antineoplastic, or immunomodulatory treatment within 6 months of study drug
  • Coinfection with active hepatitis A or B virus, or with human immunodeficiency virus (HIV)
  • Chronic liver disease other than CHC infection
  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: NCT00192647

  Show 51 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00192647     History of Changes
Other Study ID Numbers: ML17908 
Study First Received: September 13, 2005
Results First Received: May 6, 2016
Last Updated: May 6, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

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
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016