Clinical trial NCT00641654: Combination Therapy With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After Therapy With Pegylated Interferon and Ribavirin
Official title: An Open-label Multicenter Study Evaluating the Efficacy and Safety of 24 or 48 Weeks Pegylated Interferon Alfa-2a 40 kD (PEGASYS) Combination Therapy With Ribavirin (Copegus) in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After a Minimum of 12 Weeks and a Maximum of 24 Weeks of Therapy With Pegylated Interferon and Ribavirin
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Hepatitis C
Keywords: Chronic hepatitis C
genotype 2 or 3
relapse
pegylated interferon
ribavirin
Lead sponsor: Göteborg University
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2008-03-24
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of pegylated interferon alfa-2a 40 kD (PEGASYS) combination therapy with ribavirin (Copegus)given for 24 or 48 weeks in patients with chronic hepatitis C (CHC) virus infection genotype 2 or 3 who responded during (i.e. had HCV-RNA \<50 IU/mL at the end of previous therapy), but relapsed after (i.e. had detectable HCV-RNA after the end of prior treatment) previous therapy with pegylated interferon and ribavirin given for at least 12 weeks and at most 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Male and female patients ≥ 18 years of age
* Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
* Serum HCV-RNA ≥ 15 IU/mL. HCV genotype 2 or/and 3 infection confirmed within the past 6 months preceding the initiation of test drug dosing. The HCV genotype must have been reconfirmed after the termination of the previous treatment period
* Previous relapse (i.e. HCV-RNA \< 50 IU/mL at end of previous therapy) after one treatment period with pegylated interferon alfa-2a or alfa-2b combination therapy with ribavirin for at least 12 weeks and at most 24 weeks
* A minimum of 24 weeks must have elapsed since the last dose of pegylated interferon or ribavirin in the previous treatment period before the patients can be included in this study
* Compensated liver disease (Child-Pugh Grade A clinical classification)
* Patients with suspected cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP \< 100 ng/mL within 2 months of randomization
* Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
* All fertile males and females receiving ribavirin must be using effective contraception during treatment and during the 6 months after treatment end
* Having a liver biopsy obtained within 5 years of this study is encouraged, but optional in accordance with local treatment traditions.

Exclusion Criteria:

* Women with ongoing pregnancy or breast feeding
* Previous non-response during treatment (as defined as having detectable HCV RNA ≥ 50 IU/ml at the end of previous treatment) with pegylated interferon alfa-2a or alfa-2b combination therapy with ribavirin for at least 12 weeks and at most 24 weeks
* Less than 24 weeks have elapsed since the last dose of pegylated interferon or ribavirin in the previous treatment period prior to inclusion in this study.
* Therapy with any systemic anti-viral

  * anti-neoplastic
  * immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤ 6 months prior to the first dose of study drug
* Any investigational drug ≤ 6 weeks prior to the first dose of study drug. HCV genotype 1, 4, 5 or 6 infection
* Positive test at screening for anti-HAV IgM Ab

  * HBsAg
  * anti-HBc IgM Ab
  * anti-HIV Ab
* Evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
* History or other evidence of decompensated liver disease
* Neutrophil count \< 1500 cells/mm3 or platelet count \< 75,000 cells/mm3 at screening
* Serum creatinine level \> 2 mg/dl (\> 124 µmol/L) or creatinine clearance \< 50 ml/minute at screening
* Severe psychiatric disease, especially depression, as judged by the treating physician
* History of a severe seizure disorder or current anticonvulsant use
* History of immunologically mediated disease

  * severe chronic pulmonary disease associated with functional limitation
  * severe cardiac disease
  * major organ transplantation or other evidence of severe illness
  * malignancy
  * any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
* Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range)
* Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or

  * clinically relevant ophthalmological disorder due to diabetes mellitus or
  * hypertension
* Evidence of drug abuse (including excessive alcohol consumption) in accordance with local therapeutic traditions. (Patients receiving Methadone or Subutex therapy may be included in this study.)
* Inability or unwillingness to provide informed consent or abide by the requirements of the study
* Male partners of women who are pregnant
* Hemoglobin \< 11.3 g/dL (\< 7.0 mmol/L) in women or \< 12.9 g/dL (\< 8.0 mmol/L) in men at screening.
* Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, etc) or for whom anemia would be medically problematic
* 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 ribavirin therapy) would not be well-tolerated

Primary outcomes:
measure: Sustained viral response (SVR) rate defined as percentage of patients with non-detectable HCV-RNA 24 weeks after completion of the 24 or 48 week treatment period.
timeFrame: 24 weeks after completion of the 24 or 48 week treatment period.
Secondary outcomes:
measure: Sustained viral response (SVR)rate and percentage of patients with normal serum ALT levels and its association with prespecified factors e.g. viral load
timeFrame: 24 weeks after complection of the 24 or 48 week treatment
Other outcomes:
Locations:
city: Goteborg
country: Sweden
facility: Dept of Infectious Diseases, Sahlgrenska University Hospital
Study officials:
affiliation: Sahlgrenska University Hospital,Göteborg University
name: Gunnar PE Norkrans, MD Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lagging M, Rembeck K, Rauning Buhl M, Christensen P, Dalgard O, Farkkila M, Hellstrand K, Langeland N, Lindh M, Westin J, Norkrans G. Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse. Scand J Gastroenterol. 2013 Jul;48(7):839-47. doi: 10.3109/00365521.2013.793389.