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

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02716779
• Other study ID #: ML19301
• Secondary ID: 2006-000935-86
• Status: Completed
• Phase: Phase 2
• First received: March 18, 2016
• Last updated: March 22, 2016
• Start date: April 2007
• Est. completion date: April 2010

Study information

• Verified date: March 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices (BfArM)
• Study type: Interventional

Clinical Trial Summary

This study will examine the influence of ribavirin on the initial virological response in treatment-naïve participants with chronic hepatitis C, genotype 1. Participants will be 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 will receive combination therapy with PEG-IFN alfa-2a plus ribavirin (Copegus) for 12 weeks. If there is an initial virological response after 12 weeks of combination therapy, treatment may be continued for a further 36 weeks outside of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Pegylated Interferon (PEG-INF) alfa-2a
Participants with chronic hepatitis C, genotype 1 will receive Pegylated Interferon (PEG-INF) alfa-2a (40KD) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks. Thereafter, all participants will receive combination therapy with PEG-INF alfa-2a (40KD) plus ribavirin (1000 to 1200 milligram [mg] orally [PO]) for 12 weeks which may be followed further for 36 weeks depending on initial virological response.
• Placebo
Participants with chronic hepatitis C, genotype 1 will receive ribavirin matching placebo PO for 6 weeks.
• Ribavirin
Participants with chronic hepatitis C, genotype 1 will receive ribavirin monotherapy, 1000 mg PO (400 mg in the morning [=2 tablets] and 600 mg in the evening [=3 tablets]), in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, orally daily for 6 weeks. Thereafter, all participants will receive combination therapy with PEG-INF alfa-2a (40KD) plus ribavirin (1000 to 1200 mg PO) for 12 weeks which may be followed further for 36 weeks depending on initial virological response.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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		Up to Day 126	No
Secondary	Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire		Up to Day 126	No
Secondary	Percentage of Participants with Treatment Response		Up to Day 126	No
Secondary	Area Under the Serum Concentration-Time Curve (AUC) of Ribavirin		Up to Day 126	No
Secondary	Maximum Serum Concentration (Cmax) of Ribavirin		Up to Day 126	No
Secondary	Time to Maximum Concentration (tmax) of Ribavirin		Up to Day 126	No
Secondary	Area Under the Serum Concentration-Time Curve (AUC) of PEG-IFN		Up to Day 126	No
Secondary	Maximum Serum Concentration (Cmax) of PEG-IFN		Up to Day 126	No
Secondary	Time to Maximum Concentration (tmax) of PEG-IFN		Up to Day 126	No
Secondary	Area Under the Serum Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT)		Up to Day 126	No
Secondary	Maximum Serum Concentration (Cmax) of GPT		Up to Day 126	No
Secondary	Time to Maximum Concentration (tmax) of GPT		Up to Day 126	No