Thymosin Alpha-1 in Combination With Peg-Interferon Alfa- 2a and Ribavirin for the Therapy of Chronic Hepatitis C Nonresponsive to the Combination of IFN and Ribavirin.
- Conditions
- Chronic Hepatitis C
- Interventions
- Registration Number
- NCT01178996
- Lead Sponsor
- sigma-tau i.f.r. S.p.A.
- Brief Summary
The purpose of the study was to determine safety and efficacy of 48 weeks treatment with Thymosin alpha 1 (Talpha1) in combination with pegylated interferon (PEGIFN) alpha2a and ribavirin (RBV) in adult patients with chronic hepatitis C (CHC) already treated with, and not responding to previous courses of PEGIFN alpha plus RBV combination therapy, in comparison with a concurrent group treated with PEG IFN alpha2a in combination with RBV and placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 552
- Signed written informed consent
- Age 18
- Presence of HCV RNA measured by quantitative PCR
- Non responder to previous approved doses of therapy with PEGinterferon alpha plus ribavirin. Patients must have been treated for at least 12 weeks with documented HCV RNA quantitative not showing major of 2 log10 HCV RNA reduction or patients treated for at least 24 weeks with documented HCV RNA qualitative not showing a virological response (viral RNA clearance)
- Liver biopsy consistent with a diagnosis of chronic hepatitis C or histological cirrhosis. Biopsy will not be required if the patient can produce a biopsy performed within the year preceding the randomization day and was performed at least 6 months after the end of the latter course of therapy
- Wash-out period of at least 6 months from previous therapy with PEGinterferon alpha plus ribavirin
- Negative pregnancy test prior (no more than 24 hours) to first study medication dose
- Use of systemic corticosteroids within 6 months of entry
- More than one previous course of therapy with PEGinterferon alpha plus ribavirin
- Any other liver disease
- Decompensated liver disease based on a history of hepatic encephalopathy, bleeding oesophageal varices, or ascites
- Decompensate or advanced liver cirrhosis (ChildPugh B or C)
- HIV infection diagnosed by HIV seropositivity and confirmed by Western blot
- Insulin-dependent Diabetes Mellitus
- Severe haemoglobinopathy
- Positive liver and kidney microsomal auto antibodies
- Positive anti thyroid antibodies
- Pregnancy as documented by a urine pregnancy test
- Alcohol or intravenous drug abuse within the previous 1 year
- Patients who are in poor medical or psychiatric conditions, or who have any non-malignant systemic disease that, in the opinion of the Investigator, would make it unlikely that the patient could complete the study protocol
- Any indication that the patient would not comply with the conditions of the study protocol
- Previous treatment with thymosin alpha 1
- Patients with known hypersensitivity to any PEGinterferon and or ribavirin
- Patients with a history of severe depression that required either hospitalization or electroshock therapy or depression associated with suicide attempt
- Simultaneous participation in another investigational drug study or participation in any clinical trial involving investigational drugs within 3 months before study entry
- Presence of serious pulmonary or cardiovascular disorders
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Thymosin alpha 1 Thymosin alpha 1 Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). Thymosin alpha 1 PEGinterferon alfa2a Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). Placebo PEGinterferon alfa2a Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). Placebo Placebo Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). Thymosin alpha 1 Ribavirin Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin). Placebo Ribavirin Patients affected by chronic hepatitis C not responding to a course with approved doses of PEGinterferon alpha plus ribavirin therapy (i.e. at least 1.0 mcg/kg PEGinterferon alpha2b, 180 mcg PEGinterferon alfa2a, 800 mg ribavirin).
- Primary Outcome Measures
Name Time Method Sustained Virological Response (SVR) Week 72 The proportion of patients who were HCV RNA negative at the end of observation period.
- Secondary Outcome Measures
Name Time Method Sustained Biochemical Response (SBR) Week 72 The proportion of patients with normal serum ALT at the end of observation period.
End of Treatment Biochemical Response (EBR) Week 48 The proportion of patients with normal serum ALT at the end of treatment period.
End of Treatment Virological Response [EVR] Week 48 The proportion of patients who were HCV RNA negative at the end of treatment period.
Safety During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks) Safety and tolerability were evaluated by AEs recording, laboratory (hematology and chemistry), ECG, and vital signs evaluations. All laboratory tests were centralized.
Trial Locations
- Locations (9)
Università Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista
🇮🇹Turin, Italy
Hospital del Mar
🇪🇸Barcelona, Spain
Hôpital Necker
🇫🇷Paris, France
Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
University Hospital of Ioannina
🇬🇷Ioannina, Greece
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
Ospedale Cardarelli
🇮🇹Napoli, Italy