Retreatment With High Doses of pegIFN Alfa-2a and Ribavirin of Previous Nonresponders HIV-coinfected Patients With Cirrhosis Due to HCV 1-4

NCT01006031 | Completed Phase 2 DMC

• 1 other identifier: HEPAVIR_IFN_2009
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

Brief Summary

Objective: To evaluate the efficacy and safety of high doses of both peginterferon-alfa 2a (360 ug per week) plus ribavirin (800 mg b.i.d.) in HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(\*) to a standard dose treatment of both drugs. (\*) Non previous virological response: no decrease of plasma RNA-HCV at least 2 log10 after 12 weeks in treatment or breakthrough viremia while on treatment. Additionally, this study will evaluated the influence of simultaneous peginterferon-alfa 2a and ribavirin plasma concentrations on early viral response (EVR) and sustained viral response (SVR) in these patients. Method: Pilot clinical trial, phase II-III, open labeled multicenter in which patients from several hospitals of the Servicio Andaluz de Salud will be enrolled. The usual clinical and analytical follow up will be performed but additional blood samples will be obtained for determination of interferon and ribavirin plasma levels. The primary end point will be a sustained virologic response (defined as an undetectable serum HCV-RNA after 24 weeks after the cessation of treatment). Likewise, rapid virological response (at 4 weeks of treatment), early virological response (at 12 weeks), and end of treatment response rates will be evaluated as well as their relationships with the plasma interferon an ribavirin concentrations determined by ELISA and HPLC, respectively. The safety and tolerability of the studied medications will be evaluated by means of clinical adverse events, physical examination and laboratory results. The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry.

Conditions

Liver Cirrhosis; Hepatitis C Virus; HIV Infection

Keywords

Liver cirrhosis; Hepatitis C virus; HIV infection; Pegylated interferon alfa-2a; Ribavirin; Treatment experienced

Outcome Measures

Primary Outcomes (1)

• Sustained viral response (undetectable serum HCV-RNA)

  Throughout treatment and 24 weeks after finishing it

Secondary Outcomes (3)

• Relationships between the plasma interferon an ribavirin concentrations and efficacy

  Throughout treatment and 24 weeks after finishing it.

• safety and tolerability of the studied medications

  Throughout treatment and 24 weeks after finishing it

• The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry

  baseline and after finishing treatment

Study Arms (1)

PegIFN alfa-2a and Ribavirin

EXPERIMENTAL

HIV-coinfected patients with compensated cirrhosis by hepatitis C virus, genotype 1 or 4.

Drug: Pegylated interferon alfa-2a and Ribavirin

Interventions

Pegylated interferon alfa-2a and Ribavirin DRUG

Pegylated interferon alfa-2a (360 ug per week) plus oral Ribavirin (800 mg b.i.d.) for 48 or 72 weeks. The treatment will be discontinued for patients who did not achieve a reduction with respect to baseline of at least 0.5 log10 IU/ml in plasma RNA-HCV levels at week 4 or 2 log10 UI/ml at week 12 and will be considered as viral failures. Duration: 48 weeks for patients reaching an undetectable plasma RNA\_HCV at week12 and 72 weeks for those without a negative viremia at week 12 but a reduction of at least 2 log10 IU/ml in RNA-HCV levels.

Also known as: Pegasys, Copegus

PegIFN alfa-2a and Ribavirin

Eligibility Criteria

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

You may qualify if:

• Age older than 18 years
• HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(\*) to a standard dose treatment of both drugs.
• Women of child-bearing age: negative pregnancy test
• Ability to understand and sign a written consent form

You may not qualify if:

• HCV genotypes different to 1 or 4
• Acute or chronic hepatitis B infection (positivity for hepatitis B surface antigen or plasma DNA) or other concomitant causes of liver disease
• Pregnancy or breast feeding.
• Decompensated liver disease at baseline.
• Neutropenia \<1000/uL, anemia \<100 g/L or thrombocytopenia \<20.000/uL.
• Creatinine clearance \< 50 mL/min.
• Concomitant treatment with immunomodulators or zidovudine, didanosine or stavudine.
• Organ or bone marrow transplantation
• Current alcoholism or iv drug abuse. Methadone is allowed.
• Current neoplasm and/or anti-tumor chemotherapy or immunomodulators
• Psychosis or uncontrolled clinical depression
• Auto-immune disease, including auto-immune hepatitis
• History of significant cardiovascular disease (NYHA III-IV) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure.
• Thyroid dysfunction.
• Clinically significant retinal abnormalities

Sponsors & Collaborators

• Sociedad Andaluza de Enfermedades Infecciosas: lead

Study Sites (4)

Hospital Universitario Reina Sofía

Córdoba, Spain

Location

Hospitales Universitarios Virgen del Rocío

Seviila, Spain

Location

Hospital Universitario de Valme

Seville, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

MeSH Terms

Conditions

Liver Cirrhosis; Hepatitis C; HIV Infections

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Luis F Lopez-Cortes, MD, PhD

  Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocío

  STUDY DIRECTOR

• Luis F Lopez-Cortes, MD, PhD

  Instituto de Biomedicina de Sevilla. Hospitales Universitarios Virgen del Rocio

  PRINCIPAL INVESTIGATOR

• Antonio Rivero, MD, PhD

  Hospital Universitario Reina Sofia. Cordoba

  PRINCIPAL INVESTIGATOR

• Mª Jose Rios-Villegas, MD, PhD

  Hospital Universitario Viren MAcarena. Sevilla

  PRINCIPAL INVESTIGATOR

• Juan A. Pineda, MD, PhD

  Hospital Universitario de Valme. Sevilla

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Luis Fernando Lopez-Cortes

Study Record Dates

• First Submitted: October 29, 2009
• First Posted: November 2, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 30, 2011

Record last verified: 2011-12

Locations

ES (4)