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.

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Chronic Hepatitis C	Biological: Thymosin alpha 1; Drug: Ribavirin; Biological: PEGinterferon alfa2a; Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	552 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Phase III, Multicentre, Double Blinded Study In Patients With Chronic Hepatitis C Who Are Non-Responders To Prior Peginterferon Alpha + Ribavirin Therapy Comparing Treatment With Thymosin Alpha 1 + Peginterferon Alpha-2a Plus Ribavirin With Peginterferon Alpha-2a + Ribavirin + Placebo
Study Start Date :	December 2004
Actual Primary Completion Date :	May 2008
Actual Study Completion Date :	July 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 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).	Biological: Thymosin alpha 1; Thymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks.; Other Name: Zadaxin Drug: Ribavirin; Ribavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks; Other Name: Copegus Biological: PEGinterferon alfa2a; 180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks; Other Name: Pegasys
Placebo Comparator: 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).	Drug: Ribavirin; Ribavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks; Other Name: Copegus Biological: PEGinterferon alfa2a; 180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks; Other Name: Pegasys Drug: Placebo; Placebo

Outcome Measures

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Primary Outcome Measures :

1. Sustained Virological Response (SVR) [ Time Frame: Week 72 ]
   The proportion of patients who were HCV RNA negative at the end of observation period.

Secondary Outcome Measures :

1. Sustained Biochemical Response (SBR) [ Time Frame: Week 72 ]
   The proportion of patients with normal serum ALT at the end of observation period.
2. End of Treatment Biochemical Response (EBR) [ Time Frame: Week 48 ]
   The proportion of patients with normal serum ALT at the end of treatment period.
3. End of Treatment Virological Response [EVR] [ Time Frame: Week 48 ]
   The proportion of patients who were HCV RNA negative at the end of treatment period.
4. Safety [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Signed written informed consent
2. Age 18
3. Presence of HCV RNA measured by quantitative PCR
4. 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)
5. 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
6. Wash-out period of at least 6 months from previous therapy with PEGinterferon alpha plus ribavirin
7. Negative pregnancy test prior (no more than 24 hours) to first study medication dose

Exclusion Criteria:

1. Use of systemic corticosteroids within 6 months of entry
2. More than one previous course of therapy with PEGinterferon alpha plus ribavirin
3. Any other liver disease
4. Decompensated liver disease based on a history of hepatic encephalopathy, bleeding oesophageal varices, or ascites
5. Decompensate or advanced liver cirrhosis (ChildPugh B or C)
6. HIV infection diagnosed by HIV seropositivity and confirmed by Western blot
7. Insulin-dependent Diabetes Mellitus
8. Severe haemoglobinopathy
9. Positive liver and kidney microsomal auto antibodies
10. Positive anti thyroid antibodies
11. Pregnancy as documented by a urine pregnancy test
12. Alcohol or intravenous drug abuse within the previous 1 year
13. 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
14. Any indication that the patient would not comply with the conditions of the study protocol
15. Previous treatment with thymosin alpha 1
16. Patients with known hypersensitivity to any PEGinterferon and or ribavirin
17. Patients with a history of severe depression that required either hospitalization or electroshock therapy or depression associated with suicide attempt
18. Simultaneous participation in another investigational drug study or participation in any clinical trial involving investigational drugs within 3 months before study entry
19. Presence of serious pulmonary or cardiovascular disorders

Contacts and Locations

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Locations

France
Hôpital Necker
Paris, France, 75743
Germany
Universitätsklinikum Tübingen
Tübingen, Germany, D-72076
Greece
University Hospital of Ioannina
Ioannina, Greece, 45 500
Italy
Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia, Italy, 71013
Policlinico S.Orsola-Malpighi
Bologna, Italy, 40138
Ospedale Cardarelli
Napoli, Italy, 80131
Università Cattolica del Sacro Cuore
Rome, Italy, 00100
Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista
Turin, Italy, 10126
Spain
Hospital del Mar
Barcelona, Spain, 08003

Sponsors and Collaborators

sigma-tau i.f.r. S.p.A.

SciClone Pharmaceuticals

Investigators

Principal Investigator:	Mario Rizzetto, MD	Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista, Corso Bramante 88, Turin, Italy

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ciancio A, Andreone P, Kaiser S, Mangia A, Milella M, Solà R, Pol S, Tsianos E, De Rosa A, Camerini R, McBeath R, Rizzetto M. Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role? J Viral Hepat. 2012 Jan;19 Suppl 1:52-9. doi: 10.1111/j.1365-2893.2011.01524.x.

Responsible Party:	Alfonso De Rosa Clinical Research Manager, Sigma-tau SPA
ClinicalTrials.gov Identifier:	NCT01178996 History of Changes
Other Study ID Numbers:	ST1472-DM-03-004; 2004-001277-25 ( EudraCT Number )
First Posted:	August 10, 2010
Last Update Posted:	August 10, 2010
Last Verified:	August 2010

Additional relevant MeSH terms:

Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections	Ribavirin; Peginterferon alfa-2a; Interferon-alpha; Peginterferon alfa-2b; Thymalfasin; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; Antineoplastic Agents