Interest of Ribavirin in the Maintenance Treatment of Liver Fibrosis Using Low Dose Pegylated Interferon alpha2b in Patients With Chronic Hepatitis C Non Responders to Previous Antiviral Therapy.

NCT00323804 | Completed Phase 2 DMC

• 2 other identifiers: ANRS HC15 NRfi2005-002937-11
• Study Type: interventional
• Target: 372
• Locations: 2 countries
• Sites: 45

Brief Summary

Patients with chronic hepatitis C who did not respond to previous antiviral treatment develop liver fibrosis leading to cirrhosis. Maintenance low dose pegylated interferon therapy of fibrosis is currently under investigation in large multicenter trials. The aim of our study is to assess if peginterferon alpha2b plus ribavirin is more efficient than peginterferon alpha2b alone. 454 patients will be randomized between the 2 arms and the efficacy will be assessed, after 3 years of treatment, on Metavir liver fibrosis score improvement.

Conditions

Hepatitis C, Chronic; Liver Fibrosis

Keywords

Maintenance therapy; Non-responder patients; Ribavirin/peginterferon combination therapy; Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• Rate of patients with at least a one point improvement in Metavir fibrosis score between the inclusion and the end-of-study liver biopsies.

  Screen visit and M36

Secondary Outcomes (9)

• Distribution of the Metavir scoring on the end-of-study biopsy

  M36

• Distribution of the Chevallier fibrosis score

  Screen visit and M36

• Evolution of the area of fibrosis between the inclusion and the end-of -study biopsies

  Screen visit and M36

• Fibrosis serum markers

  Screen, day0, M6, M12, M24, M36

• Liver elasticity before and after treatment

  Screen,M12, M24, M36

Study Arms (2)

Randomised PegIFN alfa 2b + ribavirin (RBV) arm

EXPERIMENTAL

Combination of ribavirin capsules 200 mg, weight-based daily dose ( \<75 kg : 1000 mg ; ≥ 75 kg : 1200 mg), and low-dose PegIFN alfa 2b by subcutaneous injection 0.5 μg / kg / week, from day 0 to M36

Biological: Peginterferon alfa-2b; Drug: Ribavirin

Randomised PegIFN alfa 2b + ribavirin-placebo arm

PLACEBO COMPARATOR

Combination of ribavirin-placebo capsules 200 mg, weight-based daily dose ( \<75 kg : 1000 mg ; ≥ 75 kg : 1200 mg), and low-dose PegIFN alfa 2b by subcutaneous injection 0.5 μg / kg / week, from day 0 to M36

Biological: Peginterferon alfa-2b; Drug: Ribavirin-Placebo

Interventions

Peginterferon alfa-2b BIOLOGICAL

PegIFN alfa 2b in addition to ribavirin or ribavirin-placebo, from day 0 to M36

Randomised PegIFN alfa 2b + ribavirin (RBV) arm; Randomised PegIFN alfa 2b + ribavirin-placebo arm

Ribavirin DRUG

Ribavirin in addition to PegIFN alfa 2b, from day 0 to M36

Randomised PegIFN alfa 2b + ribavirin (RBV) arm

Ribavirin-Placebo DRUG

Ribavirin-placebo in addition to PegIFN alfa 2b, from day 0 to M36

Randomised PegIFN alfa 2b + ribavirin-placebo arm

Eligibility Criteria

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

You may qualify if:

• Adults over 18
• With a hepatitis C virus infection (HCV RNA and anti-HCV antibodies in serum)
• Not responders to a previous antiviral treatment using the interferon plus ribavirin combination
• With a wash-out of treatment for at least 6 months
• With an active chronic hepatitis C and a Metavir fibrosis score ≥ 2
• Accepting to undergo a liver biopsy at the end of the study
• Negative pregnancy test for women
• With a social security cover
• Written informed consent

You may not qualify if:

• History of hepatic complications
• History of transplantation
• History of severe seizures
• History of severe psychiatric disorders
• Drug addiction within the last 12 months
• Associated condition susceptible to be responsible for liver fibrosis
• Hepatocellular carcinoma
• Cardiovascular disease unstable under treatment
• Uncontrolled diabetes
• Retinopathy
• Thyroid disease unstable under treatment
• Epilepsy and/or central nervous system functional disorders
• Autoimmune disease
• Regular alcohol consumption
• Pregnancy, breast-feeding or absence of contraception

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Merck Sharp & Dohme LLC: collaborator
• Rennes University Hospital: collaborator

Study Sites (45)

CHU Brugmann

Brussels, 1020, Belgium

Location

Hôpital Bracops

Brussels, 1070, Belgium

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Hôpital de Jolimont

La Louvière, 7100, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

Service d'Hépatogastroentérologie et d'endoscopie digestive - CH du Pays d'Aix

Aix-en-Provence, 13616, France

Location

Hôpital Nord

Amiens, 80054, France

Location

Service d'Hépatogastroentérologie - Hôpital Nord

Amiens, 80054, France

Location

Service d'Hépatologie - Gastroentérologie - Cancérologie digestive - CHU Angers

Angers, 49100, France

Location

Centre Hospitalier Victor Dupouy

Argenteuil, 95100, France

Location

Service d'Hépatogastroentérologie - Hôpital Avicenne

Bobigny, 93009, France

Location

Service d' Hépatogastroentérologie - Hôpital Jean Verdier

Bondy, 93143, France

Location

Service d'Hépatogastroentérologie et d'Assistance nutritive - Hôpital Haut-Lévêque

Bordeaux Pessac, 33604, France

Location

CH Pierre OUDOT

Bourgoin, 38317, France

Location

Service d'Hépatogastroentérologie - Hôpital de la Cavale Blanche

Brest, 29200, France

Location

Service d'Hépatologie - Gastroentérologie - Nutrition -Hôpital de la Côte de Nacre

Caen, 14000, France

Location

Centre Hospitalier

Châteauroux, 36000, France

Location

Service d'Hépatogastroentérologie - CHU d'ESTAING

Clermont-Ferrand, 63003, France

Location

Service d'Hépatogastroentérologie - Hôpital Beaujon

Clichy, 92110, France

Location

Service d'Hépatogastroentérologie - CH Sud Francilien

Corbeil-Essonnes, 91106, France

Location

Service d'Hépatogastroentérologie - Hôpital du Bocage

Dijon, 21079, France

Location

Hôpital Nord

Grenoble, 38043, France

Location

Service d'Hépatogastroentérologie - CH La Roche sur Yon

La Roche-sur-Yon, 85925, France

Location

Service des Maladies du Foie et de l'appareil Digestif - Hôpital de Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Département d'Hépatogastroentérologie - CH Le Mans

Le Mans, 72037, France

Location

Service d'Hépatogastroentérologie - CHRU - Hôpital Claude Huriez

Lille, 59000, France

Location

Service d'Hépatogastroentérologie - Hotel de la Croix Rousse

Lyon, 69004, France

Location

Service d'Hépatogastroentérologie - Hôpital Saint Joseph

Marseille, 13285, France

Location

Service d'Hépatogastroentérologie - CH Montauban

Montauban, 82000, France

Location

Service d'Hépatogastroentérologie - CH Montélimar

Montélimar, 26200, France

Location

Service d'Hépatogastroentérologie - Hôpital Saint Eloi

Montpellier, 34295, France

Location

Service d'Hépatogastroentérologie - Hôtel Dieu

Nantes, 44093, France

Location

Hôpital de l'Archet

Nice, 06202, France

Location

Service d'Hépatogastroentérologie - Hôpital de la Source

Orléans, 45067, France

Location

Service d'Hépatogastroentérologie - Hôpital La Pitié Salpétrière

Paris, 75013, France

Location

Service d'Hépatogastroentérologie - Hôpital Tenon

Paris, 75020, France

Location

Service d'Hépatogastroentérologie - Hôpital Pontchaillou

Rennes, 35033, France

Location

Service d'Hépatogastroentérologie - CHU Rouen

Rouen, 76031, France

Location

Centre Hospitalier

Saint-Quentin, 02321, France

Location

Service d'Hépatogastroentérologie, Clinique médicale B - Hôpital Civil

Strasbourg, 67000, France

Location

Hôpital Purpan

Toulouse, 31059, France

Location

Service d'Hépatogastroentérologie - Hôpital Purpan

Toulouse, 31059, France

Location

Service d'Hépatogastroentérologie - Hôpital Trousseau

Tours, 37044, France

Location

Service d'Hépatogastroentérologie - Hôpital Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Hôpita Paul Brousse

Villejuif, 94804, France

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Liver Cirrhosis

Interventions

peginterferon alfa-2b; 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; Fibrosis

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Dominique Guyader, MD, PhD

  CHU Rennes

  PRINCIPAL INVESTIGATOR

• Eric Bellissant, MD, PhD

  CHU Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2006
• First Posted: May 10, 2006
• Study Start: May 1, 2006
• Primary Completion: February 1, 2013
• Study Completion: March 1, 2013
• Last Updated: September 4, 2014

Record last verified: 2014-08

Locations

BE (5); FR (40)