A Study of Peginterferon Alfa-2a (Pegasys) When Administered in Combination With Ribavirin in Patients With Chronic Hepatitis C (CHC)

Roche

Status and phase

Completed

Phase 4

Conditions

Hepatitis C, Chronic

Treatments

Drug: Ribavirin

Drug: Peginterferon alfa-2a

Study type

Interventional

Funder types

Industry

Identifiers

NCT02641379

ML17131

Details and patient eligibility

About

This study will compare the efficacy and safety of 2 different treatment durations of peginterferon alfa-2a (Pegasys) plus ribavirin in patients with CHC. The anticipated time on study treatment is 1-2 years, and the target sample size is greater than (>) 500 individuals.

Enrollment

737 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male and female patients with chronic hepatitis C and genotype 1 (1a or 1b) or genotype 4
Age between 18 and 70 years
Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
Present with at least one elevated serum alanine-aminotransferase (ALT) level higher than normal in the last 6 months before therapy start including the screening period
Positive HCV-RNA level in serum
Laboratory parameters (within 35 days prior to study start): -Hepatitis A anti - IgM negativity, HIV-Ab negativity, HBsAg negativity, Hemoglobin values > 12 g/dl in women or > 13 g/dl in men, Leukocyte count (WBC) > 3 000 /mcl, Platelets count > 100 000/mcl, Creatinine not 1.5 times higher than normal, normal TSH, normal uric acid with a maximum tolerance of 15 % in patients without history of gout
Liver biopsy findings within 6 months prior to study therapy consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis. Biopsies older than 1 year are eligible only after direct communication with the principal investigator
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. If there is no laboratory report existing, the physician should make an entry in the medical history that the pregnancy test was negative.
All fertile females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end. All fertile men with female partners must be using two forms of effective contraception during treatment and during the 7 months after treatment end.
Written informed consent obtained

Exclusion criteria

Any IFN and / or Pegylated IFN and ribavirin therapy at any previous time
Class B or C cirrhosis as coded by Child Pugh classification
Women with ongoing pregnancy or breast feeding
Therapy with any systemic anti-neoplastic or 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
Drug addiction within 1 year prior to study start (patients participating in an official methadone program are eligible)
Diabetes mellitus in patients receiving an insulin therapy
Hemophiliac patients (due to the increased risk of requested liver biopsy)
History or other 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 bleeding from esophageal varices or other conditions consistent with decompensated liver disease
History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease. Exception: if there is a current psychiatric report which certifies there is no contraindication to interferon therapy, patient may be included
History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis etc.)
History or other evidence of chronic pulmonary disease associated with functional limitation
History of a severe seizure disorder or current anticonvulsant use
History of severe cardiac disease and severe coronary heart disease within the last 6 months (angina pectoris, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia). If there is clinical suspicion of coronary heart disease cardiologic workup of the patient prior to study entry is recommended.
History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
History of major organ transplantation with an existing functional graft
Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
Inability or unwillingness to provide informed consent or abide by the requirements of the study

Additional exclusion criteria concerning ribavirin:

Male partners of women who are pregnant
Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, history of GI bleeding, 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 would not be well-tolerated

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

737 participants in 4 patient groups

PEG-IFN 24 weeks

Experimental group

Description:

Participants will receive PEG-IFN (180 microgram \[mcg\]), subcutaneously (sc), once weekly for 24 weeks and Ribavirin 1000-1200 milligram per day (mg/day) (\<75 kilogram (kg); \>75 kg) for 24 weeks.

Treatment:

Drug: Peginterferon alfa-2a

Drug: Ribavirin

PEG-IFN 24/72 weeks

Experimental group

Description:

Participants will receive PEG-IFN (180 mcg), sc, once weekly and Ribavirin 1000-1200 mg/day (\<75kg; \>75 kg) till week 24; if patient is still HCV RNA positive. Treatment will be stopped if participant is HCV RNA negative at week 24 -treatment with PEG-IFN (180 mcg), sc, once weekly and Ribavirin 1000-1200 mg/day (\<75kg; \>75 kg) till week 72

Treatment:

Drug: Peginterferon alfa-2a

Drug: Ribavirin

PEG-IFN 48 weeks

Experimental group

Description:

Participants will receive PEG-IFN (180 mcg), sc, once weekly for 48 weeks and Ribavirin 1000-1200 mg/day (\<75kg; \>75 kg) for 48 weeks.

Treatment:

Drug: Peginterferon alfa-2a

Drug: Ribavirin

PEG-IFN 72 weeks

Experimental group