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Latino Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) and COPEGUS (Ribavirin) in Treatment-Naive Patients With Chronic Hepatitis C-Genotype 1.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00107653
First received: April 6, 2005
Last updated: May 13, 2016
Last verified: May 2016
  Purpose
This single arm study will evaluate the efficacy and safety of PEGASYS (180 micrograms sc weekly) plus ribavirin (1000-1200mg po daily) in treatment-naive Latino patients versus non-Latino Caucasian patients with chronic hepatitis C- genotype 1. The anticipated time on study treatment is 3-12 months and the target sample size is 500+ patients.

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Open-label, Comparative, Efficacy Study of Pegasys® Plus Copegus® in Treatment-naïve Latino Patients With Chronic Hepatitis C-genotype 1, as Compared to Treatment-naïve Non- Latino Caucasian Patients With Chronic 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 Virologic Response at Week 72 [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]
    Sustained Virologic Response (SVR) is defined as percentage of participants with an undetectable hepatitis C virus-RNA (HCV-RNA) measurement (<28 International Unit (IU)/millilitre (mL)) assessed 24 weeks post-treatment (week 72) which was assessed by Roche High Pure System/COBAS TaqMan HCV Test.


Secondary Outcome Measures:
  • Percentage of Participants Achieving Virologic Response [ Time Frame: At Weeks 4, 12, 24, 48, 60, and 72 ] [ Designated as safety issue: No ]
    Percentage of participants achieving a virologic response defined as an undetectable HCV-RNA measurement (HCV-RNA <28 IU/mL by Roche High Pure System/COBAS TaqMan HCV Test)

  • Percentage of Participants With Early Virologic Response at Week 4 [ Time Frame: At Week 4 ] [ Designated as safety issue: No ]
    Percentage of participants with an early virologic response defined as an HCVRNA >=1 log10 drop from baseline or undetectable HCV-RNA measurement at Week 4 (lower limit of detection 28 IU/mL).

  • Percentage of Participants With Early Virologic Response at Week 12 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    Percentage of participants with an early virologic response defined as an HCV-RNA >=2 log10 drop from baseline or undetectable HCV-RNA measurement at Week 12 (lower limit of detection 28 IU/mL).

  • Change From Baseline in HCV-RNA Log10 Titers Over the Period Of Time [ Time Frame: From Baseline (Week 0) to Weeks 4, 12, 24, 48, 60 and 72 ] [ Designated as safety issue: No ]
    The table below shows HCV-RNA log10 titers change from baseline values by study week and by study group. Analysis was performed for participants with a baseline and at least 1 post-baseline HCV-RNA assessment. HCV-RNA quantitation was performed using Roche High Pure System/COBAS® TaqMan® HCV Monitor Test. HCV-RNA measurement lower limit of detection was 28 IU/mL.

  • Percentage of Participants With Biochemical Response [ Time Frame: At Weeks 4, 12, 24, 48, 60 and 72 ] [ Designated as safety issue: No ]
    Biochemical response was defined as normal serum alanine transaminase (ALT) measurement. For ALT measurement the normal range is 5-37 IU/L.

  • Percentage of Participants With ISHAK Histological Activity Index Response [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]
    ISHAK Histological Activity Index (HAI) activity response is defined as a decrease from baseline of at least 2 points (≥2 points drop from baseline) in the ISHAK modified HAI (necroinflammatory) score at week 72. ISHAK modified HAI activity (necroinflammatory) score is a total score of periportal ± bridging (P/B) necrosis + confluent necrosis + focal necrosis + portal inflammation (maximum score for each participant = 18). Where P/B necrosis grading as 0 = absent; 1 = mild; 2 = mild/moderate; 3 = moderate; 4 = severe; Confluent necrosis grading as 0 = absent; 1 = focal; 2 = zone 3 some areas; 3 = zone 3 most areas; 4 = zone 3 occasional portal; 5 = zone 3 multiple; 6 = panacinar necrosis and Focal necrosis grading as 0: absent; 1: < = 1 focus; 2: 2 to 4 foci; 3: 5 to 10 foci; 4: > 10 foci; Portal Inflammation grading: 0 = none; 1 = mild; 2 = moderate; 3 = moderate/marked; 4 = marked/all portal.

  • Mean Change From Baseline in ISHAK HAI Activity (Necroinflammatory) at Week 72 [ Time Frame: From Baseline (Week 0) to Week 72 ] [ Designated as safety issue: No ]
    ISHAK modified HAI activity (necroinflammatory) score is a total score of P/B necrosis + confluent necrosis + focal necrosis + portal inflammation (maximum score for each Participant = 18). Where P/B necrosis grading as 0 = absent; 1 = mild; 2 = mild/moderate; 3 = moderate; 4 = severe; Confluent necrosis as 0 = absent; 1 = focal; 2 = zone 3 some areas; 3 = zone 3 most areas; 4 = zone 3 occasional portal; 5= zone 3 multiple; 6= panacinar necrosis and Focal necrosis as 0: absent; 1: <= 1 focus; 2: 2 to 4 foci; 3: 5 to 10 foci; 4: > 10 foci; Portal Inflammation: 0 = none; 1 = mild; 2 = moderate; 3 = moderate/marked; 4 = marked/all portal. The difference between study groups in change from baseline in ISHAK modified HAI activity score at week 72 was tested using an analysis of covariance (ANCOVA) model with ethnicity and baseline ISHAK HAI score as the fixed effects.

  • Mean Change From Baseline in Fibrosis Score Based on ISHAK at Week 72 [ Time Frame: From Baseline (Week 0) to Week 72 ] [ Designated as safety issue: No ]
    ISHAK Histological Activity Index (HAI) activity response is defined as a decrease from baseline of at least 2 points (≥2 points drop from baseline) score at week 72. Baseline prognostic factors in the original model include ethnicity, sex, age, baseline ALT quotient, baseline HCV-RNA level, and ISHAK fibrosis and activity scores at baseline. ISHAK modified HAI fibrosis scale by fibrosis grading category as F0= no fibrosis; F1= some portal areas; F2= most portal areas; F3= bridging fibrosis; F4= bridging and portal to central; F5 = marked bridging; F6 = Cirrhosis; where '0' being the best and '6' being the worst. Decrease in score from baseline indicates improvement. The difference between study groups in change from baseline in ISHAK modified HAI activity score at week 72 was analysed.

  • Percentage of Participants With Improved, Stable and Worsened ISHAK Fibrosis Score [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]
    Overall ISHAK Fibrosis Score is defined as Improved: >= 1 category decrease in fibrosis scale; Stable: no change in fibrosis scale; Worsened: >1 category increase in fibrosis scale.

  • Mean Change From Baseline in Activity and Fibrosis Scores Based on METAVIR Activity at Week 72 [ Time Frame: From Baseline (Week 0) to Week 72 ] [ Designated as safety issue: No ]
    METAVIR activity scores are categorised as histological activity (A) 0 = none; A1 = mild; A2 = moderate; A3 = severe where '0' being 'No activity' and '3' being 'the sever activity'. Changes in liver inflammation defined as Improved: Participants whose METAVIR activity score at up to Month-72 decreases by 1 or more units compared to baseline; stable: Participants whose METAVIR activity score at up to Month-72 is the same as the baseline score; worsened: Participants whose METAVIR activity score at up to Month-72 increases by 1 or more units compared to baseline. METAVIR fibrosis scores are categorised as fibrosis (F) 0 = no fibrosis; F1 = without septa; F 2 = with septa; F3 = many septa; F4 = cirrhosis where; '0' being the best and '4' being the worst. Decrease in score from baseline indicates improvement. The difference between study groups in change from baseline in activity and fibrosis scores based on METAVIR at week 72 was analysed.

  • Percentage of Participants With Improved, Stable, and Worsened METAVIR Activity Score [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]
    METAVIR activity scale included activity defines as, Improved: >= 1 category decrease in activity score; stable: no change in activity score; worsened: > = 1 category increase in activity score.

  • Percentage of Participants With Improved, Stable, and Worsened METAVIR Fibrosis Score [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]
    METAVIR fibrosis score is categorized as, Improved: >= 1 category decrease in activity score; stable: no change in activity score; worsened: >= 1 category increase in activity score.

  • Mean Change From Baseline in Fat Score at Week 72 [ Time Frame: From Baseline (Week 0) to Week 72 ] [ Designated as safety issue: No ]
    Grading categories for the fat scale were as follows: 1 = <5% hepatocytes; 2 = 6 - 33% hepatocytes; 3 = 34 - 66% hepatocytes; 4 = 67 - 100% hepatocytes.

  • Percentage of Participants With Improved, Stable and Worsened Fat Score From Baseline to Week 72 [ Time Frame: From Baseline (Week 0) to Week 72 ] [ Designated as safety issue: No ]
    Fat scores are categorised as Improved: > 1 category decrease in fat scale; stable: no change in fat scale; worsened: >= 1 category increase in fat scale.

  • Percentage of Participants With Non-zero Nonalcoholic Steatohepatitis Score [ Time Frame: At Week 72 ] [ Designated as safety issue: No ]
    The Nonalcoholic Steatohepatitis (NASH) included an assessment of sinusoidal fibrosis, Mallory bodies, and hepatocyte ballooning (HB). Grading categories for the NASH scales were as: Sinusoidal fibrosis: 0 = absent; 1 = involvement of some lobules; 2 = involvement of most lobules, without diffuse interstitial sinusoidal collagen deposition; 3 = Involvement of most or all lobules;, with diffuse interstitial fibrosis involving some or most of the lobules Mallory bodies: 0 = absent; 1 = involvement of some lobules; 2 = involvement of most lobules; 3= involvement of most or all lobules; and Hepatocyte ballooning: 0 = absent; 1 = involvement of some lobules; 2 = involvement of most lobules; 3= involvement of most or all lobules.

  • Mean Change in Fatigue Severity Scale Score and Fatigue Severity Scale Score Item 10 Visual Analog Scale Score From Baseline at Week 48 and Week 72 [ Time Frame: Baseline (Week 0), Week 48 and Week 72 ] [ Designated as safety issue: No ]
    The Fatigue Severity Scale (FSS) is a 10-item self-report questionnaire designed to assess tiredness, lack of energy, or total body give-out. Participants were to react to nine statements regarding fatigue over the previous 2 weeks, each on a scale (1 = completely agree, 7 = completely disagree). The FSS is the average of the scores on the 9 questions; ranging from 1-7, with lower scores indicating less fatigue. In addition, participants were to react to how much fatigue they had in the past 2 weeks by marking on a visual analogue scale (VAS) labelled at one end with "no fatigue" ('0' being the best) and at the other end with "greater fatigue" ('100' being the worst). Longer distance on the scale from "no fatigue" indicated "greater fatigue". FSS values are presented based on questionnaire and visual analog scale. FSS values at week 48 and 72 are presented based on questionnaire and visual analog scale.

  • Mean Change in 36-item Short Form Health Survey Total and Domain Scores From Baseline at Week 48 and 72 [ Time Frame: Baseline (Week 0), Week 48 and Week 72 ] [ Designated as safety issue: No ]
    The 36-item Short Form Health Survey (SF-36) is a 36-item self-report questionnaire that includes 8 domain scales The 8 domains are incorporated into 2 components: mental and physical. The mental component (MC) includes social functioning, role limitations-emotional, mental health, and vitality. The physical component (PC) includes physical functioning, role limitations-physical, bodily pain, and general health perception. Raw domain scores are transformed to a 0 to 100 scale, [0=worst score (or quality of life) and 100=best score]. Two summary scale scores were computed based on weighted combinations of the 8 domain scores (Physical and the Mental Component) where no minimum or maximum score; higher score indicate better health status. The difference between study groups in change from baseline in SF-36 score at week 48 and 72 was analysed.

  • Number of Participants With Any Adverse Events and Serious Adverse Events [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An adverse event could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions that worsened during the study were reported as adverse events. A serious adverse event (SAE) was any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of hospitalization, or results in disability/incapacity, or congenital anomaly/birth defect.

  • Number of Participants With Marked Abnormal Laboratory Parameters [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    The below table includes participants with marked abnormal lab parameters. Standard reference ranges include: Hematocrit: (fraction) 0.37 - 0.49, Hemoglobin 130 - 180 g/L, Platelets 150 - 350 10^9/L, White Blood Cell (WBC) 4.5 - 11.0 10^9/L, Lymphocytes 1.00 - 4.80 10^9/L, Neutrophils 1.80 - 7.70 10^9/L, Aspartate aminotransferase (AST) 0-40 U/L, ALT 0 - 55 U/L, Total bilirubin 0 - 17 μmol/L, Thyroxine T4 58 - 140 nmol/L, Thyroid Stimulating Hormone (TSH) 0.0 - 5.0 million units (mU)/L, Albumin 35.0 - 55.0 g/L, Chloride 100 - 108 mmol/L, Calcium 2.10 - 2.60 mmol/L, Phosphate 0.84 - 1.45 mmol/L, Uric acid 214 - 506 μmol/L.

  • Number of Participants With Premature Withdrawals Due to Adverse Events or Laboratory Abnormalities [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    The table below includes participants with premature withdrawals due to adverse events or laboratory abnormalities.


Enrollment: 569
Study Start Date: October 2004
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Latino
Participants received peginterferon alfa-2a 180 microgram (mcg)/0.5 mL by subcutaneous injection once a week in combination with ribavirin 1000 or 1200 mg per day, which was taken orally in split doses for 48 weeks. Participants with <75 kg (165 lbs) of body weight received 1000 mg/day (400 mg in the morning and 600 mg in the evening). Participants with >=75 kg (165 lbs) of body weight received 1200 mg/day (600 mg in the morning and 600 mg in the evening).
Drug: Ribavirin
1000-1200mg po daily for 48 weeks
Drug: Peginterferon alfa-2a
180 micrograms sc/week for 48 weeks
Experimental: Non-Latino White
Participants received peginterferon alfa-2a 180 mcg/0.5 mL by subcutaneous injection once a week in combination with ribavirin 1000 or 1200 mg per day which was taken orally in split doses. Participants with <75 kg (165 lbs) of body weight received 1000 mg/day. Participants with >=75 kg (165 lbs) of body weight received 1200 mg/day for 48 weeks.
Drug: Ribavirin
1000-1200mg po daily for 48 weeks
Drug: Peginterferon alfa-2a
180 micrograms sc/week for 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients 18-65 years of age
  • chronic hepatitis C , genotype 1
  • serologic evidence of CHC infection by an antibody test
  • chronic liver disease, consistent with CHC infection on a liver biopsy obtained within the past 18 months
  • compensated liver disease
  • use of 2 forms of contraception during the study in both men and women

Exclusion Criteria:

  • previous interferon or ribavirin therapy
  • systemic antiviral therapy less than 24 weeks before first dose of study drug or expected need for this treatment any time during the study
  • medical condition associated with chronic liver disease (eg, hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure)
  • decompensated liver disease
  • women who are pregnant or breastfeeding
  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: NCT00107653

  Show 60 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00107653     History of Changes
Other Study ID Numbers: ML18179 
Study First Received: April 6, 2005
Results First Received: March 16, 2016
Last Updated: May 13, 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
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 December 07, 2016