A Randomized, Multicenter, Double Blinded, Phase IV Study Comparing the Safety and Efficacy of Pegasys 180 µg plus Copegus 1000 or 1200 mg to the Currently Approved Combination of Pegasys 180 µg plus Copegus 800 mg in Interferon-naïve Patients with Chronic Hepatitis C Genotype 1 virus infection coinfected with human immunodeficiency virus (HIV-1).

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005506-23-PT
• Date of registration: 24/04/2006
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Randomized, Multicenter, Double Blinded, Phase IV Study Comparing the Safety and Efficacy of Pegasys 180 µg plus Copegus 1000 or 1200 mg to the Currently Approved Combination of Pegasys 180 µg plus Copegus 800 mg in Interferon-naïve Patients with Chronic Hepatitis C Genotype 1 virus infection coinfected with human immunodeficiency virus (HIV-1).
• Scientific title: A Randomized, Multicenter, Double Blinded, Phase IV Study Comparing the Safety and Efficacy of Pegasys 180 µg plus Copegus 1000 or 1200 mg to the Currently Approved Combination of Pegasys 180 µg plus Copegus 800 mg in Interferon-naïve Patients with Chronic Hepatitis C Genotype 1 virus infection coinfected with human immunodeficiency virus (HIV-1).
• Date of first enrolment: 04/08/2006
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005506-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Portugal, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
• Male and female patients >= 18 years of age
• Serological evidence of CHC infection by an anti-HCV antibody test (current or historical)
• Detectable plasma HCV-RNA (>600 IU/mL)
• Evidence of HCV genotype 1 infection by molecular assay
• Chronic liver disease consistent with CHC infection on a biopsy obtained within the past 18 months as judged by a central pathologist. Up to 20% of patients with cirrhosis or incomplete cirrhosis will be allowed to enter the trial
• Child Pugh total score at screening must be equal to 5 for a patient with cirrhosis or bridging fibrosis/transition to cirrhosis to be enrolled into NV18209. The only exception would be an elevation in Child Pugh total score (of >= 6) secondary to total bilirubin as a consequence of a concomitant medication (e.g. atazanavir and indinavir) or a clinical condition (e.g. Gilbert's syndrome) that may cause hyperbilirubinemia. An elevation in Child Pugh total score (of >= 6) secondary to albumin, INR, ascites or hepatic encephalopathy will not be acceptable
• Patients with cirrhosis or incomplete cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma (within 2 months of randomization) and a serum alpha-fetoprotein (AFP) <100 ng/mL
• Serological evidence of HIV-1 infection by HIV-1 antibody or detection of HIV-1 RNA
• Clinically stable status of HIV-1 infection in the opinion of the investigator, ie, patients who are not expected to progress during the study
• Patients with a CD4+ count >= 100 cells/µL
• Patients with HIV disease who are receiving stable antiretroviral therapy (ART) or for whom antiretroviral therapy is not required.
• Negative urine or blood pregnancy test result (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug.
Additionally, all males with female partners of childbearing potential and sexually active females of childbearing potential must be using two forms of effective contraception (combined) during treatment and during the 6 months after treatment end.
• Willingness to give written informed consent and willingness to participate in and comply with the study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• History of having received alpha IFNs, PEG-IFN, ribavirin (RBV), viramidine, levovirin or investigational HCV protease or polymerase inhibitors at any previous time. Any history of systemic antiviral therapy, with established or perceived activity against HCV, =< 3 months prior to the first dose of study medication
• Infection with any HCV genotype other than genotype 1 or infection with a mixed genotype or with a genotype that can not be established as genotype 1, i.e. ndeterminant genotype
• History or other evidence of decompensated liver disease or a Child-Pugh score >5.
Coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• Positive test result at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab
• History or other evidence of a medical condition associated with chronic liver disease other than HCV
• Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is >= 20% within 2 years. Patients with liver cirrhosis with a lesion suspicious for hepatic malignancy on the screening imaging study will be eligible only if the likelihood of carcinoma is =<10% following an appropriate evaluation
• Active HIV-related opportunistic infection and/or malignancy requiring acute systemic therapy
• Within 6 weeks of starting the study screening period, the use of colony stimulating factors , such as granulocyte colony stimulating factor (GCSF) or erythropoietin to elevate hematology parameters. (These factors may be used after treatment has commenced)
• Absolute neutrophil count (ANC) <1500 cells/mm3, except for African-Americans whose ANC should not be <1200 cells/mm3
• Platelet count <70,000 cells/mm3
• Hemoglobin <11 g/dL in females or <12 g/dL in males or any patient with a aseline
increased risk for anemia (eg, thalassemia, sickle cell anemia, spherocytosis, history
of GI bleeding) or for whom anemia would be medically problematic.
• Serum creatinine level >1.5 times the upper limit of normal at screening
• History of severe psychiatric disease including psychosis and or depression, a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease
• History of uncontrolled severe seizure disorder
• History of immunologically mediated disease (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis (defined as affecting > 10% of the body, where the palm of one hand equals 1%, or if the hands and feet are affected), rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management
• History or other evidence of chronic pulmonary disease associated with functional limitation
• History of significant cardiac disease that could be worsened by acute anemia (eg, NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases). In addition, patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with RBV therapy) would not be well-tolerated
• Poorly controlled thyroid dysfunction
• History or other ev

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with chronic hepatitis C (CHC) genotype 1 virus coinfected with human immunodeficiency virus type 1 (HIV-1)

Intervention(s)

Product Name: Pegasys
Product Code: RO 25-8310
Pharmaceutical Form: Solution for injection

Product Name: Copegus
Product Code: RO 20-9963
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Primary Efficacy
• To compare the efficacy of treatment with Copegus (ribavirin (RBV)) 1000 or 1200 mg in combination with Pegasys (peginterferon alfa-2a (PEG-IFN alfa-2a)) 180 µg to the approved regimen of Copegus 800 mg in combination with Pegasys 180 µg in patients with chronic hepatitis C genotype 1 virus coinfected with HIV-1 treated for 48 weeks and followed for 24 weeks after treatment end (sustained virologic response, SVR)

Primary Safety
• To compare the safety of treatment with Copegus 1000 or 1200 mg in combination with Pegasys 180 µg to the approved regimen of Copegus 800 mg in combination with Pegasys 180 µg in patients with chronic hepatitis C genotype 1 virus coinfected with HIV-1 treated for 48 weeks and followed for 24 weeks after treatment end

Secondary Objective: Secondary Safety
• To evaluate the safety profile of both regimens in patients of non-Hispanic African American descent.

Primary end point(s): The primary efficacy variable is sustained virological response, as defined by the percentage of patients with undetectable HCV RNA at 24 weeks after completion of the 48 week treatment period (ie, a single last HCV RNA < 20 IU/mL measured >= study day 477 ( >= week 68).

Secondary ID(s)

2005-005506-23-ES

NV18209