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An Observational Study of Peginterferon (e.g. Pegasys)-Based Direct Acting Antiviral Triple Therapy in Patients With Chronic Hepatitis C Genotype 1

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01508130
First received: January 9, 2012
Last updated: January 25, 2016
Last verified: January 2016
  Purpose
This prospective observational study will evaluate the efficacy and safety of two approved pegylated interferon-based direct acting antiviral triple therapies in patients with chronic hepatitis C genotype 1. Patients receiving pegylated interferon (e.g. Pegasys) and ribavirin plus either telaprevir or boceprivir in accordance with local standard of care and US labeling will be followed for the duration of their treatment and for up to 24 weeks post-treatment.

Condition
Hepatitis C, Chronic

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Non-Interventional, Prospective Cohort Study of the Effectiveness, Safety and Utilization of Two Approved Pegylated Interferon-Based Direct Acting Antiviral Triple Therapies in the Management of Genotype 1 Chronic Hepatitis C in Routine Clinical Practice in the USA

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Time to Premature Treatment Discontinuation Due to Any Reason [ Time Frame: Up to the treatment discontinuation or the date of the last dosing for participants who were ongoing or completed the study treatment (including those who shorten the treatment based on response-guided therapy) ] [ Designated as safety issue: No ]
    Time to premature treatment discontinuation for any reason (weeks) was calculated as follows: date of treatment discontinuation for any reason - first treatment administration date + 1/7. The estimated survivorship curves were obtained from Kaplan-Meier maximum likelihood estimates for each treatment group. Participants who completed the study treatment (including those who shorten the treatment based on response-guided therapy) were censored on their last dosing date.

  • Number of Participants With Sustained Virologic Response (SVR) at 12 Weeks or Later After Completion of the Treatment Period [ Time Frame: 12 weeks or later post-completion of the treatment period ] [ Designated as safety issue: No ]
    SVR rate defined as the number of participants with undetectable HCV RNA (i.e., HCV RNA less than 50 IU/mL) at 12 weeks or later post-completion of the treatment period


Secondary Outcome Measures:
  • Number of Participants With Virologic Response (VR) [ Time Frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48; and 12 weeks post-completion of treatment period ] [ Designated as safety issue: No ]
    VR was defined as undetectable HCV RNA (i.e.,HCV RNA less than 50 IU/mL)

  • Number of Participants With VR by Categories of Very Rapid VR (VRVR), Rapid Virological Response (RVR), VR Week 8, Early Virological Response (cEVR), Partial Virological Response (pEVR), and None of the Above [ Time Frame: Weeks 2, 4, 8, and 12 ] [ Designated as safety issue: No ]
    VRVR was defined as HCV RNA < 50 IU/mL at treatment Week 2; RVR as HCV RNA < 50 IU/mL by treatment Week 4, but no HCV RNA < 50 IU/mL at Week 2; Week 8 VR as HCV RNA < 50 IU/mL by study Week 8 but no HCV RNA < 50 IU/mL at Weeks 2 to 4; cEVR as HCV RNA < 50 IU/mL by treatment Week 12 but no HCV RNA < 50 IU/mL at Weeks 2 to 8; and pEVR as at least a 2 log10 decrease in HCV RNA by treatment Week 12 but no HCV RNA < 50 IU/mL at Weeks 2 to 12.

  • Number of Participants Who Achieved Extended VR, Virologic Breakthrough/Rebound, Virologic Relapse, and Who Were Non-responder [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    The extended VR is defined as initial HCV RNA < 50 IU/mL during Weeks 2 to 24 and remaining HCV RNA < 50 IU/mL at all subsequent assessments; virologic breakthrough/rebound is defined as detectable HCV RNA during the treatment period in participants with prior non-detectable HCV RNA or increase of HCV RNA by >=1 log10 above nadir for direct-acting antiviral (DAA) tripe therapies (PegIFN + RBV + TEL or PegIFN + RBV + BOC); virologic relapse is defined as detectable HCV RNA during the treatment-free follow-up period in participants with HCV RNA < 50 IU/mL at EoT; non-responder is defined as participants who never achieved undetectable HCV-RNA during the 48 weeks of treatment.

  • Predictors of Sustained Virologic Response by Week [ Time Frame: Weeks 2, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    SVR rate defined as the number of participants with undetectable HCV RNA (i.e., HCV RNA less than 50 IU/mL) at 12 weeks or later post-completion of the treatment period. The predictors defined as participants with virological response (HCV RNA < 50 IU/mL at any visit), or with virological response at Week 12 (HCV-RNA < 50 IU/mL or unquantifiable or HCV-RNA >=2 log10 drop from baseline). Positive predictive value is the probability that participants with a positive screening test truly have the disease. Negative predictive value is the probability that participants with a negative screening test truly don't have the disease.

  • Number of Participants With SVR by Subgroups (Demographic and Baseline Factors) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Participants for VR to prior therapy (PegIFN + RBV) were categorized as: relapse (who completed the previous treatment with HCV RNA undetectable, but relapsed with detectable HCV RNA once treatment was discontinued), breakthrough (HCV RNA undetectable, followed by detectable HCV RNA during on-treatment period), null responder (completed at least 12 weeks of treatment with HCV RNA decrease < 2 log10 at Week 12), partial responder (HCV RNA decrease > 2 log10 by Week 12 of treatment and HCV RNA remained detectable), unknown response (completed previous treatment, but treatment response based on HCV RNA determinations was not available), and prior intolerant (treated previously, but discontinued due to adverse event or participant's choice prior to completion of therapy). Participants categorized into 3 genotypes (CC, CT and TT) based on single nucleotide polymorphism in the Interleukin 28B (IL28B) gene.

  • Duration of Viral Undetectability During Treatment for Participants With HCV RNA Undetectable During Treatment by Trial Treatment [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    The undetectable HCV RNA means HCV RNA values less than 50 IU/mL. This outcome measure was calculated as the duration of participant's first date of undetectable HCV RNA and the date of the participant's last dose.

  • Time to Premature Treatment Discontinuation Due to Lack of Efficacy [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    The participants discontinued the study treatment due to lack of efficacy of study treatment. Time to premature treatment discontinuation due to lack of efficacy (weeks) = (date of treatment discontinuation due to lack of efficacy - first treatment administration date + 1)/7. Participants who were ongoing or completed the study treatment (including those who shortened the treatment based on response-guided therapy) were censored at the date of their last dosing.

  • Time to Premature Treatment Discontinuation Due to Intolerance [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    The participants discontinued the study treatment due to intolerance of the study treatment. Time to premature treatment discontinuation due to intolerance (weeks) = (date of treatment discontinuation due to lack of intolerance - first treatment administration date + 1)/7. Participants who were ongoing or completed the study treatment (including those who shortened the treatment based on response-guided therapy) were censored at the date of their last dosing.

  • Treatment Duration, as Measure of Extent of Exposure to Study Medication [ Time Frame: From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48) ] [ Designated as safety issue: No ]
    Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to PegIFN alfa-2a, PegIFN alfa-2b, ribavirin, telaprevir, and boceprevir is calculated as the number of weeks between the start and end of treatment.

  • Mean Cumulative Dose, as Measure of Extent of Exposure to Study Medication [ Time Frame: From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48) ] [ Designated as safety issue: No ]
    Extent of exposure is defined as the duration of the treatment administered during the study. The mean cumulative doses of PegIFN alfa-2a, PegIFN alfa-2b, ribavirin, telaprevir, and boceprevir were presented.

  • Percentage of Dose Reduction, as Measure of Extent of Exposure to Study Medication [ Time Frame: From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48) ] [ Designated as safety issue: No ]
    Extent of exposure is defined as the duration of the treatment administered during the study. Degree of dose reduction was calculated as actual exposure/target exposure × 100%. Target exposure was defined as the actual received treatment duration multiplied by the initial assigned dose. Actual exposure was defined as cumulative dose during the treatment period.

  • Compliance of Study Treatment [ Time Frame: Weeks 4, 8, 12, and 24 ] [ Designated as safety issue: No ]
    Compliance was assessed based on the number of participants who received the planned study treatment (PegIFN alfa-2a, PegIFN alfa-2b, ribavirin, telaprevir, and boceprevir) during the treatment period.

  • Number of Participants Treated With PegIFN, RBV, and TEL as Per the U.S. Label [ Time Frame: Up to 48 weeks (included 12 weeks of triple therapy + additional 12/36 weeks of dual therapy) ] [ Designated as safety issue: No ]
    As per the U.S. labeling, participants with treatment-naive, prior relapse (TN-PR) and prior partial or null responder (PP/NR) received PegIFN + RBV + TEL (triple therapy) for 12 weeks; followed additional 12 or 36 weeks of PegIFN + RBV (dual therapy) depending on viral response and prior response status.

  • Number of Participants Treated With PegIFN, RBV, and BOC as Per the U.S. Label [ Time Frame: Up to 48 weeks (included 4 weeks of dual therapy + additional 28/36 weeks of triple therapy and/or additional dual therapy up to Week 48) ] [ Designated as safety issue: No ]
    As per the U.S. labeling, participants with cirrhosis (C); non-cirrhotic/treatment-naïve (NC/TN); and non-cirrhotic/previous partial responders or relapsers (NC/PPR or R) received first 4 weeks of dual therapy, followed by additional 28 or 36 weeks of PegIFN + RBV + BOC (triple therapy) and/or then completed dual therapy through Week 48 depending on viral response and prior response status.

  • Number of Participants With Safety-related Dose Reductions [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    The dose reduction was done because of safety-related reasons (AEs) including alanine aminotransferase disorder, anemia, neutropenia, thrombocytopenia, and rash.

  • Number of Participants With Premature Treatment Discontinuation Due to Adverse Events (AEs) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product.

  • Number of Participants With Any AEs and Serious Adverse Events (SAEs) [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.

  • Change From Baseline in Work Loss And Productivity Outcomes (WPAI) [ Time Frame: Baseline (Day 1 ), Weeks 2, 4, 6, 8, 12, 16, 24, 36, 48, 12 weeks post-treatment ] [ Designated as safety issue: No ]
    WPAI-AS is a 6-question participant rated questionnaire to determine the amount of absenteeism, presenteeism, work productivity loss and daily activity impairment attributable to ankylosing spondylitis for a period of 7 days prior to each visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Each sub-scores was scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity.


Enrollment: 672
Study Start Date: January 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with chronic hepatitis C genotype 1 receiving pegylated interferon-based direct acting antiviral triple therapies in the US
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Chronic hepatitis C, genotype 1
  • Receiving pegylated interferon-based direct acting antiviral therapy (pegylated interferon and ribavirin plus either telaprevir or boceprivir) in accordance with local standard of care and US labeling

Exclusion Criteria:

  • Contraindications per US labels
  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: NCT01508130

  Show 63 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01508130     History of Changes
Other Study ID Numbers: ML27900 
Study First Received: January 9, 2012
Results First Received: October 19, 2015
Last Updated: January 25, 2016
Health Authority: United States: Food and Drug 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
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 23, 2016