An Observational Study of Peginterferon (e.g. Pegasys)-Based Direct Acting Antiviral Triple Therapy in Patients With Chronic Hepatitis C Genotype 1
- Conditions
- Hepatitis C, Chronic
- Registration Number
- NCT01508130
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 672
- 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
- Contraindications per US labels
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time to Premature Treatment Discontinuation Due to Any Reason 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) 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 12 weeks or later post-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
- Secondary Outcome Measures
Name Time Method Predictors of Sustained Virologic Response by Week Weeks 2, 4, 6, 8, and 12 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) Week 12 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.
Number of Participants With Virologic Response (VR) Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48; and 12 weeks post-completion of treatment period VR was defined as undetectable HCV RNA (i.e.,HCV RNA less than 50 IU/mL)
Percentage of Dose Reduction, as Measure of Extent of Exposure to Study Medication From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48) 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 Weeks 4, 8, 12, and 24 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 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 Weeks 2, 4, 8, and 12 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 Treated With PegIFN, RBV, and TEL as Per the U.S. Label Up to 48 weeks (included 12 weeks of triple therapy + additional 12/36 weeks of dual therapy) 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 With Any AEs and Serious Adverse Events (SAEs) Up to 12 weeks post-treatment 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) Baseline (Day 1 ), Weeks 2, 4, 6, 8, 12, 16, 24, 36, 48, 12 weeks post-treatment 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.
Number of Participants Who Achieved Extended VR, Virologic Breakthrough/Rebound, Virologic Relapse, and Who Were Non-responder Up to Week 48 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.
Duration of Viral Undetectability During Treatment for Participants With HCV RNA Undetectable During Treatment by Trial Treatment Up to Week 48 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 Up to Week 48 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.
Number of Participants With Safety-related Dose Reductions Up to 48 weeks 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) Up to 48 weeks 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.
Mean Cumulative Dose, as Measure of Extent of Exposure to Study Medication From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48) 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.
Time to Premature Treatment Discontinuation Due to Intolerance Up to Week 48 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 From the date of the first dose of the study drug up to withdrawal/study completion (up to Study Week 48) 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.
Number of Participants Treated With PegIFN, RBV, and BOC as Per the U.S. Label 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) 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.
Trial Locations
- Locations (66)
Florida Center for Gastroenterology
🇺🇸Largo, Florida, United States
HMRI Liver Center
🇺🇸Pasadena, California, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Litchfield County Gastroenterology Associates
🇺🇸Torrington, Connecticut, United States
Ochsner Clinic Foundation
🇺🇸Baton Rouge, Louisiana, United States
Liver Wellness Center
🇺🇸Little Rock, Arkansas, United States
Mercy Medical Center; Institute For Digestive Health And Liver Disease
🇺🇸Baltimore, Maryland, United States
Consultive Medicine
🇺🇸Daytona Beach, Florida, United States
Loma Linda University Medical Center and Liver Center
🇺🇸Loma Linda, California, United States
South Bay Gastroenterology Medical Group
🇺🇸Torrance, California, United States
Atlanta Center for Gastroenterology, PC
🇺🇸Decatur, Georgia, United States
New Orleans Research Institute.
🇺🇸Metairie, Louisiana, United States
Dartmouth Hitchcock Med Center
🇺🇸Lebanon, New Hampshire, United States
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico
Tristate Gastroenerology Associates
🇺🇸Crestview Hills, Kentucky, United States
Bend Memorial Clinic
🇺🇸Bend, Oregon, United States
Lourdes Medical Associates; Southern New Jersey Center for LIver Disease
🇺🇸Haddon Heights, New Jersey, United States
Commonwealth Clinical Studies
🇺🇸Brockton, Massachusetts, United States
Mountainview Medical Practice
🇺🇸Catskill, New York, United States
AGA Clinical Research Associates, LLC
🇺🇸Twp, New Jersey, United States
Concorde Medical Group
🇺🇸New York, New York, United States
Asheville Gastroenterology Associates, P.A.
🇺🇸Asheville, North Carolina, United States
Indianapolis Gastroenterology
🇺🇸Indianapolis, Indiana, United States
Digestive And Liver Disease Consultants, PA
🇺🇸Houston, Texas, United States
Kaiser Permanente San Diego; Hepatology Research
🇺🇸San Diego, California, United States
VA San Diego Healthcare System
🇺🇸San Diego, California, United States
Cooper Green Hospital
🇺🇸Birmingham, Alabama, United States
Univ. of Alabama at Birmingham; The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
Harper University Hospital/Wayne State
🇺🇸Detroit, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Duke Univ Medical Center
🇺🇸Durham, North Carolina, United States
Dekalb Gastroenterology Associates
🇺🇸Decatur, Georgia, United States
Center for Advanced Gastroenterology
🇺🇸Maitland, Florida, United States
Baystate Infectious Diseases Clinical Research
🇺🇸Springfield, Massachusetts, United States
New York Methodist Hospital
🇺🇸Brooklyn, New York, United States
New Discovery, LLC
🇺🇸Flushing, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Albert Einstein Medical Center; Division of Hepatology
🇺🇸Philadelphia, Pennsylvania, United States
Methodist Heathcare University Hospital
🇺🇸Memphis, Tennessee, United States
Methodist Transplant Physicians
🇺🇸Dallas, Texas, United States
Imtiaz Alam MD, P.A. - Private Practice
🇺🇸Austin, Texas, United States
Univ of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Liver Associates of Texas
🇺🇸Houston, Texas, United States
University of Virginia Health System: Gastroenterology at UVA
🇺🇸Charlottesville, Virginia, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Gastroenterology Associates of Western Michigan
🇺🇸Wyoming, Michigan, United States
Kelsey Research Foundation
🇺🇸Houston, Texas, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Gastroenterology Associates of Central Georgia
🇺🇸Macon, Georgia, United States
Tulane Uni Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Partners in Internal Medicine
🇺🇸Worcester, Massachusetts, United States
DuBois Regional Medical Center
🇺🇸DuBois, Pennsylvania, United States
Metropolitan Research
🇺🇸Fairfax, Virginia, United States
Atlantic Research Affiliates
🇺🇸Morristown, New Jersey, United States
Saint Louis University Gastroenterology & Hepatology; Clinical Research Unit
🇺🇸St. Louis, Missouri, United States
INTEGRIS Baptist Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Boice-Willis Clinic
🇺🇸Rocky Mount, North Carolina, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Internal Medicine Specialists
🇺🇸Orlando, Florida, United States
Orlando Infectious Disease Center, Pa
🇺🇸Orlando, Florida, United States
Tampa General Hospital; Tampa General Medical Group
🇺🇸Tampa, Florida, United States
St. Luke's Hospital
🇺🇸Kansas City, Missouri, United States
Midwest Biomedical Research Foundation
🇺🇸Kansas City, Missouri, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States