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.

This study has been completed.
Sponsor:
Collaborator:
SciClone Pharmaceuticals
Information provided by:
sigma-tau i.f.r. S.p.A.
ClinicalTrials.gov Identifier:
NCT01178996
First received: August 9, 2010
Last updated: NA
Last verified: August 2010
History: No changes posted
  Purpose

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 Intervention Phase
Chronic Hepatitis C
Biological: Thymosin alpha 1
Drug: Ribavirin
Biological: PEGinterferon alfa2a
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by sigma-tau i.f.r. S.p.A.:

Primary Outcome Measures:
  • Sustained Virological Response (SVR) [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    The proportion of patients who were HCV RNA negative at the end of observation period.


Secondary Outcome Measures:
  • Sustained Biochemical Response (SBR) [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    The proportion of patients with normal serum ALT at the end of observation period.

  • End of Treatment Biochemical Response (EBR) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The proportion of patients with normal serum ALT at the end of treatment period.

  • End of Treatment Virological Response [EVR] [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The proportion of patients who were HCV RNA negative at the end of treatment period.

  • Safety [ Time Frame: During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks) ] [ Designated as safety issue: Yes ]
    Safety and tolerability were evaluated by AEs recording, laboratory (hematology and chemistry), ECG, and vital signs evaluations. All laboratory tests were centralized.


Enrollment: 552
Study Start Date: December 2004
Study Completion Date: July 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178996

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

No publications provided by sigma-tau i.f.r. S.p.A.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Study First Received: August 9, 2010
Last Updated: August 9, 2010
Health Authority: Italy: Ethics Committee

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
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
Thymalfasin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014