Clinical trial NCT01178996: 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.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis C
Lead sponsor: sigma-tau i.f.r. S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: SciClone Pharmaceuticals
First posted: 2010-08-10
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Sustained Virological Response (SVR)
timeFrame: Week 72
Secondary outcomes:
measure: Sustained Biochemical Response (SBR)
timeFrame: Week 72
measure: End of Treatment Biochemical Response (EBR)
timeFrame: Week 48
measure: End of Treatment Virological Response [EVR]
timeFrame: Week 48
measure: Safety
timeFrame: During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks)
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza
state: Foggia
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi
city: Napoli
country: Italy
facility: Ospedale Cardarelli
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Turin
country: Italy
facility: Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista
city: Barcelona
country: Spain
facility: Hospital del Mar
Study officials:
affiliation: Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista, Corso Bramante 88, Turin, Italy
name: Mario Rizzetto, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ciancio A, Andreone P, Kaiser S, Mangia A, Milella M, Sola 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.