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Phase 2 N=67 Randomized Double-blind Treatment

Influence of Ribavirin on the Initial Virological Response in Treatment Naïve Patients With Hepatitis C Genotype 1 Infection

Hepatitis C, Chronic

Enrolled (actual)
67
Serious AEs
3.8%
Results posted
Jul 2016
Primary outcome: Primary: Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action — -27.0; -21.4; -22.2; -28.2 log likelihood function value

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Pegylated Interferon (PEG-IFN) alfa-2a (Drug); Placebo (Drug); Ribavirin (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Apr 2010

Outcome Measures

OutcomeResultp-value
PRIMARY
Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action
-27.0; -21.4; -22.2; -28.2; -23.8; -23.9
SECONDARY
Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
95.6; 76.5; 79.7; 90.8; 72.3; 68.4
SECONDARY
Percentage of Participants With Treatment Response
79; 65; 72; 43; 30; 20
SECONDARY
Area Under the Concentration-Time Curve (AUC) of Ribavirin
186.6; 179.4; 290.1
SECONDARY
Maximum Concentration (Cmax) of Ribavirin
2.95; 2.83; 3.37
SECONDARY
Time to Maximum Concentration (Tmax) of Ribavirin
6.0; 8.0; 6.4
SECONDARY
Area Under the Concentration-Time Curve (AUC) of PEG-IFN
2097.9; 1270.4; 1164.9
SECONDARY
Maximum Concentration (Cmax) of PEG-IFN
28.77; 20.36; 19.8
SECONDARY
Time to Maximum Concentration (Tmax) of PEG-IFN
6.3; 12.0; 6.0
SECONDARY
Area Under the Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT)
5078.3; 7233.5; 5231.3
SECONDARY
Maximum Concentration (Cmax) of GPT
68.5; 88.0; 75.0
SECONDARY
Time to Maximum Concentration (Tmax) of GPT
2.8; 14.0; 3.0

Summary

This study examined the influence of ribavirin on the initial virological response in treatment-naïve participants with chronic hepatitis C, genotype 1. Participants were randomized to 1 of 3 treatment groups to receive placebo, ribavirin monotherapy 1000 milligrams (mg) to 1200 mg orally daily depending on body weight or pegylated interferon (PEG-IFN) alfa-2a (Pegasys®) 180 micrograms (mcg) subcutaneously (SC) weekly, for 6 weeks. Following the initial 6 weeks, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin (Copegus®) for 12 weeks. If there was an initial virological response after 12 weeks of combination therapy, treatment could be continued for a further 36 weeks outside of the study.

Eligibility Criteria

Inclusion Criteria

  • Caucasians, male or female aged between 18 and 70 years
  • Indication: serological proof of a chronic hepatitis C infection with positive result of anti-Hepatitis C virus (HCV) test and detectable HCV- Ribo Nucleic Acid (RNA) in serum
  • Proven HCV genotype 1 by means of the reverse hybridization assays
  • Proven histological infection activity within the liver with or without proven compensated cirrhosis within the last 24 months prior to start of the study (Child-Pugh degree A)
  • Participants without previous anti-HCV therapy

Exclusion Criteria

  • Known hypersensitivity to interferon or ribavirin or any of the other component parts
  • Pregnant or nursing women, women with child bearing potential and without using a high effective method of contraception. The urine and serum pregnancy test at visit 0 in fertile participants or cohabitants of participants must show a negative result
  • Male partners of pregnant women
  • Infection with HCV genotype 2, 3, 4, 5, or 6
  • Pretreatment with interferon and/or ribavirin
  • Immunocompromised participants
  • Treatment of systemic anti-neoplastic or immunomodulatoric medication (including supraphysiological doses of steroids or radiation therapy) within the last 6 months prior to the start of treatment and during the complete time interval of study treatment
  • Chronic hepatitis due to hepatitis C virus (e.g. haemochromatosis, autoimmunohepatitis, metabolic or alcohol-related liver disease)
  • Decompensated liver cirrhosis or liver disease Child-Pugh degree B or C or condition after decompensation
  • Signs of a hepatocellular carcinoma within 2 months prior to randomization in case of a cirrhosis or a transition to cirrhosis
  • Ascites or esophagus varices with bleedings as documented in anamnesis
  • Any medical condition that questions in the opinion of the investigator the participant's enrollment and participation in the trial
  • Hemoglobin <13 grams/deciliter (g/dl) in females and <14 g/dl in males in screening phase
  • Patients with an increased anemia risk (e.g. thalassemia, spherocytosis, etc.) or patients which would be at a particular medical risk in case of an anemia
  • Diagnosed neutropenia <1.500/microliter (mcl) or thrombocytopenia <90.000/mcl in screening phase
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02716779). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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