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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic

• Study Type: Observational
• Enrollment (Actual): 672

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion De Investigacion de Diego
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Cooper Green Hospital
    • Birmingham, Alabama, United States, 35233
      • Univ. of Alabama at Birmingham; The Kirklin Clinic
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Liver Wellness Center
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center and Liver Center
    • Pasadena, California, United States, 91105
      • HMRI Liver Center
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System
    • San Diego, California, United States, 92154
      • Kaiser Permanente San Diego; Hepatology Research
    • Torrance, California, United States, 90505
      • South Bay Gastroenterology Medical Group
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • Torrington, Connecticut, United States, 06790
      • Litchfield County Gastroenterology Associates
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Consultive Medicine
    • Largo, Florida, United States, 33777
      • Florida Center for Gastroenterology
    • Maitland, Florida, United States, 32751
      • Center For Advanced Gastroenterology
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
    • Orlando, Florida, United States, 32806
      • Orlando Infectious Disease Center, Pa
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital; Tampa General Medical Group
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Center for Gastroenterology, PC
    • Decatur, Georgia, United States, 30033
      • Dekalb Gastroenterology Associates
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indianapolis Gastroenterology
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Tristate Gastroenerology Associates
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Clinic Foundation
    • Metairie, Louisiana, United States, 70006
      • New Orleans Research Institute.
    • New Orleans, Louisiana, United States, 70112-2699
      • Tulane Uni Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center; Institute For Digestive Health And Liver Disease
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies
    • Springfield, Massachusetts, United States, 01199
      • Baystate Infectious Diseases Clinical Research
    • Worcester, Massachusetts, United States, 01068
      • Partners in Internal Medicine
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital/Wayne State
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital
    • Kansas City, Missouri, United States, 64128
      • Midwest Biomedical Research Foundation
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University Gastroenterology & Hepatology; Clinical Research Unit
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Med Center
  • New Jersey
    • Haddon Heights, New Jersey, United States, 08035
      • Lourdes Medical Associates; Southern New Jersey Center for LIver Disease
    • Morristown, New Jersey, United States, 07960
      • Atlantic Research Affiliates
    • Twp, New Jersey, United States, 08234
      • AGA Clinical Research Associates, LLC
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Catskill, New York, United States, 12414
      • Mountainview Medical Practice
    • Flushing, New York, United States, 11355
      • New Discovery, LLC
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10016
      • Concorde Medical Group
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Durham, North Carolina, United States, 27710
      • Duke Univ Medical Center
    • Rocky Mount, North Carolina, United States, 27804
      • Boice-Willis Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • DuBois Regional Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center; Division of Hepatology
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist Heathcare University Hospital
  • Texas
    • Austin, Texas, United States, 78758
      • Imtiaz Alam MD, P.A. - Private Practice
    • Dallas, Texas, United States, 75203
      • Methodist Transplant Physicians
    • Galveston, Texas, United States, 77555
      • Univ of Texas Medical Branch
    • Houston, Texas, United States, 77005
      • Kelsey Research Foundation
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas
    • Houston, Texas, United States, 77090
      • Digestive And Liver Disease Consultants, PA
  • Vermont
    • Burlington, Vermont, United States, 5401
      • University of Vermont
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System: Gastroenterology at UVA
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Premature Treatment Discontinuation Due to Any Reason	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.	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)
Number of Participants With Sustained Virologic Response (SVR) at 12 Weeks or Later After Completion of the Treatment Period	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	12 weeks or later post-completion of the treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Virologic Response (VR)	VR was defined as undetectable HCV RNA (i.e.,HCV RNA less than 50 IU/mL)	Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48; and 12 weeks post-completion of treatment period
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	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.	Weeks 2, 4, 8, and 12
Number of Participants Who Achieved Extended VR, Virologic Breakthrough/Rebound, Virologic Relapse, and Who Were Non-responder	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.	Up to Week 48
Predictors of Sustained Virologic Response by Week	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.	Weeks 2, 4, 6, 8, and 12
Number of Participants With SVR by Subgroups (Demographic and Baseline Factors)	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.	Week 12
Duration of Viral Undetectability During Treatment for Participants With HCV RNA Undetectable During Treatment by Trial Treatment	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.	Up to Week 48
Time to Premature Treatment Discontinuation Due to Lack of Efficacy	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.	Up to Week 48
Time to Premature Treatment Discontinuation Due to Intolerance	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.	Up to Week 48
Treatment Duration, as Measure of Extent of Exposure to Study Medication	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.	From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48)
Mean Cumulative Dose, as Measure of Extent of Exposure to Study Medication	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.	From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48)
Percentage of Dose Reduction, as Measure of Extent of Exposure to Study Medication	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.	From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48)
Compliance of Study Treatment	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.	Weeks 4, 8, 12, and 24
Number of Participants Treated With PegIFN, RBV, and TEL as Per the U.S. Label	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.	Up to 48 weeks (included 12 weeks of triple therapy + additional 12/36 weeks of dual therapy)
Number of Participants Treated With PegIFN, RBV, and BOC as Per the U.S. Label	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.	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)
Number of Participants With Safety-related Dose Reductions	The dose reduction was done because of safety-related reasons (AEs) including alanine aminotransferase disorder, anemia, neutropenia, thrombocytopenia, and rash.	Up to 48 weeks
Number of Participants With Premature Treatment Discontinuation Due to Adverse Events (AEs)	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.	Up to 48 weeks
Number of Participants With Any AEs and Serious Adverse Events (SAEs)	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.	Up to 12 weeks post-treatment
Change From Baseline in Work Loss And Productivity Outcomes (WPAI)	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.	Baseline (Day 1 ), Weeks 2, 4, 6, 8, 12, 16, 24, 36, 48, 12 weeks post-treatment

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2012
• Primary Completion (Actual): March 31, 2014
• Study Completion (Actual): March 31, 2014

Study Registration Dates

• First Submitted: January 9, 2012
• First Submitted That Met QC Criteria: January 9, 2012
• First Posted (Estimate): January 11, 2012

Study Record Updates

• Last Update Posted (Actual): April 10, 2017
• Last Update Submitted That Met QC Criteria: March 10, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: ML27900