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.

NCT01178996 | Completed Phase 3

• 2 other identifiers: ST1472-DM-03-0042004-001277-25
• Study Type: interventional
• Target: 552
• Locations: 5 countries
• Sites: 9

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.

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Sustained Virological Response (SVR)

  The proportion of patients who were HCV RNA negative at the end of observation period.

  Week 72

Secondary Outcomes (4)

• Sustained Biochemical Response (SBR)

  Week 72

• End of Treatment Biochemical Response (EBR)

  Week 48

• End of Treatment Virological Response [EVR]

  Week 48

• Safety

  During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks)

Study Arms (2)

Thymosin alpha 1

EXPERIMENTAL

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; Drug: Ribavirin; Biological: PEGinterferon alfa2a

Placebo

PLACEBO COMPARATOR

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; Biological: PEGinterferon alfa2a; Drug: Placebo

Interventions

Thymosin alpha 1 BIOLOGICAL

Thymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks.

Also known as: Zadaxin

Thymosin alpha 1

Ribavirin DRUG

Ribavirin 1000 mg (\<75 kg) or 1200 mg (\>75 kg) daily with food divided in two doses orally for 48 weeks

Also known as: Copegus

Placebo; Thymosin alpha 1

PEGinterferon alfa2a BIOLOGICAL

180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks

Also known as: Pegasys

Placebo; Thymosin alpha 1

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• sigma-tau i.f.r. S.p.A.: lead
• SciClone Pharmaceuticals: collaborator

Study Sites (9)

Hôpital Necker

Paris, 75743, France

Location

Universitätsklinikum Tübingen

Tübingen, D-72076, Germany

Location

University Hospital of Ioannina

Ioannina, 45 500, Greece

Location

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Ospedale Cardarelli

Napoli, 80131, Italy

Location

Università Cattolica del Sacro Cuore

Rome, 00100, Italy

Location

Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista

Turin, 10126, Italy

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Related Publications (1)

• 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.

  PMID: 22233415 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Thymalfasin; Ribavirin; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymosin; Thymus Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mario Rizzetto, MD

  Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista, Corso Bramante 88, Turin, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: August 10, 2010
• Study Start: December 1, 2004
• Primary Completion: May 1, 2008
• Study Completion: July 1, 2009
• Last Updated: August 10, 2010

Record last verified: 2010-08

Locations

GR (1); DE (1); IT (5); FR (1); ES (1)