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

NCT02716779 | Completed Phase 2 Results

• 2 other identifiers: ML193012006-000935-86
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 5

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.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• 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

  To investigate possible action mechanisms, three different models were fitted to viruskinetic data and evaluated using related log-likelihood function values. These models were designed assuming individual effects with respect to infectiousness (model 1), virus production (model 2) or degradation of infected cells rate (model 3). The following viruskinetic parameters were fitted in each model: initial viral load, loss rate of infected cells (delta), effectivity of interferon with respect to a pharmacokinetic-pharmacodynamic model. A lower log likelihood function value indicates a lesser fit for the model.

  Up to Day 126

Secondary Outcomes (11)

• Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire

  At screening (Days -56 to -1), at end of monotherapy (Week 6) and at end of combination therapy (Week 18)

• Percentage of Participants With Treatment Response

  Up to Day 126

• Area Under the Concentration-Time Curve (AUC) of Ribavirin

  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.

• Maximum Concentration (Cmax) of Ribavirin

  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.

• Time to Maximum Concentration (Tmax) of Ribavirin

  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.

Study Arms (3)

Pegylated Interferon (PEG-IFN) alfa-2a

EXPERIMENTAL

Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.

Drug: Pegylated Interferon (PEG-IFN) alfa-2a; Drug: Ribavirin

Placebo

PLACEBO COMPARATOR

Participants with chronic hepatitis C, genotype 1, received ribavirin matching placebo for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.

Drug: Pegylated Interferon (PEG-IFN) alfa-2a; Drug: Placebo; Drug: Ribavirin

Ribavirin

EXPERIMENTAL

Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.

Drug: Pegylated Interferon (PEG-IFN) alfa-2a; Drug: Ribavirin

Interventions

Pegylated Interferon (PEG-IFN) alfa-2a DRUG

Pegylated interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.

Also known as: Pegasys®

Pegylated Interferon (PEG-IFN) alfa-2a; Placebo; Ribavirin

Placebo DRUG

Ribavirin matching placebo orally (PO) twice daily for 6 weeks.

Placebo

Ribavirin DRUG

Ribavirin, 1000 mg orally (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, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.

Also known as: Copegus®

Pegylated Interferon (PEG-IFN) alfa-2a; Placebo; Ribavirin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Roche Pharma AG: collaborator

Study Sites (5)

Unknown Facility

Berlin, 13353, Germany

Location

Unknown Facility

Frankfurt am Main, 60590, Germany

Location

Unknown Facility

Frankfurt am Main, 60594, Germany

Location

Unknown Facility

Hanover, 30625, Germany

Location

Unknown Facility

Homburg/ Saar, 66424, Germany

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Stephan Zeuzem, Prof. Dr.

  Roche Pharma AG, 79639 Grenazch Wyhlen, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: March 23, 2016
• Study Start: April 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: August 22, 2016
• Results First Posted: July 14, 2016

Record last verified: 2016-03

Locations

DE (5)