Clinical trial NCT02716779: Influence of Ribavirin on the Initial Virological Response in Treatment Naïve Patients With Hepatitis C Genotype 1 Infection
Official title: Randomized, Multicentric, Partially Double-Blinded Placebo-Controlled Phase II Study for Examining the Influence of Ribavirin on the Initial Virological Response With Treatment of Peginterferon Alfa-2a (40KD) and Ribavirin With a Six Week Pretreatment-Phase of Ribavirin/Placebo or PEG-Interferon Monotherapy in Treatment Naïve Patients With Chronic Hepatitis C Virus Genotype 1 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2016-03-23
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: 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
timeFrame: Up to Day 126
Secondary outcomes:
measure: Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire
timeFrame: At screening (Days -56 to -1), at end of monotherapy (Week 6) and at end of combination therapy (Week 18)
measure: Percentage of Participants With Treatment Response
timeFrame: Up to Day 126
measure: Area Under the Concentration-Time Curve (AUC) of Ribavirin
timeFrame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
measure: Maximum Concentration (Cmax) of Ribavirin
timeFrame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
measure: Time to Maximum Concentration (Tmax) of Ribavirin
timeFrame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
measure: Area Under the Concentration-Time Curve (AUC) of PEG-IFN
timeFrame: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126
measure: Maximum Concentration (Cmax) of PEG-IFN
timeFrame: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126
measure: Time to Maximum Concentration (Tmax) of PEG-IFN
timeFrame: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126
measure: Area Under the Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT)
timeFrame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
measure: Maximum Concentration (Cmax) of GPT
timeFrame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
measure: Time to Maximum Concentration (Tmax) of GPT
timeFrame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
Other outcomes:
Locations:
city: Berlin
country: Germany
city: Frankfurt Am Main
country: Germany
city: Frankfurt Am Main
country: Germany
city: Hannover
country: Germany
city: Homburg/ Saar
country: Germany
Study officials:
affiliation: Roche Pharma AG, 79639 Grenazch Wyhlen, Germany
name: Stephan Zeuzem, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: