Chronic Hepatitis CPhase 3NCT01178996
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.
A Phase 3 study testing Thymosin alpha 1, Ribavirin and PEGinterferon alfa2a in people with Chronic Hepatitis C, run by sigma-tau i.f.r. S.p.A. at 9 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Thymosin alpha 1, Ribavirin and PEGinterferon alfa2a
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 552 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Dec 2004to Jul 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Italy5 sites
Policlinico S.Orsola-Malpighi
Bologna, 40138
Ospedale Cardarelli
Naples, 80131
Università Cattolica del Sacro Cuore
Rome, 00100
Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia, 71013
Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista
Turin, 10126
About this study
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
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
- Being tested
- Thymosin alpha 1, Ribavirin, PEGinterferon alfa2a, Placebo
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thymosin alpha 1Biological
Also called Zadaxin
Thymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks.
RibavirinDrug
Also called Copegus
Ribavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks
PEGinterferon alfa2aBiological
Also called Pegasys
180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Ribavirin; Biological: PEGinterferon alfa2a; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Virological Response (SVR)
The proportion of patients who were HCV RNA negative at the end of observation period.
Measured: Week 72
Secondary outcomes (4)
Sustained Biochemical Response (SBR)
The proportion of patients with normal serum ALT at the end of observation period.
Measured: Week 72
End of Treatment Biochemical Response (EBR)
The proportion of patients with normal serum ALT at the end of treatment period.
Measured: Week 48
End of Treatment Virological Response [EVR]
The proportion of patients who were HCV RNA negative at the end of treatment period.
Measured: Week 48
Safety
Safety and tolerability were evaluated by AEs recording, laboratory (hematology and chemistry), ECG, and vital signs evaluations. All laboratory tests were centralized.
Measured: During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2010 (estimated)
- Study startDec 2004
- Primary completionMay 2008
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 552 participants (actual)
Sponsor and investigators
- Lead sponsor
- sigma-tau i.f.r. S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SciClone Pharmaceuticals
- Investigators
- Mario Rizzetto, MD, Principal investigator, Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista, Corso Bramante 88, Turin, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01178996
- Sponsor's protocol ID
- ST1472-DM-03-004
- Other IDs
- 2004-001277-25, 2004
- Status last verified
- Aug 2010
- First submitted
- 9 Aug 2010
- Last updated
- 10 Aug 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22233415
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01178996
- Acronym / sponsor ID
- ST1472-DM-03-004
- Conditions
- Chronic Hepatitis C
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 552 participants (actual)
- Lead sponsor
- sigma-tau i.f.r. S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- SciClone Pharmaceuticals
- Study start
- Dec 2004
- Primary completion
- May 2008 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 10 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thymosin alpha 1 | Experimental | Biological: Thymosin alpha 1, Drug: Ribavirin, Biological: PEGinterferon alfa2aPatients 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 comparator | Drug: Ribavirin, Biological: PEGinterferon alfa2a, Drug: PlaceboPatients 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). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thymosin alpha 1Also: ZadaxinThymosin alpha 1 (Zadaxin) 1.6 mg/day, two times weekly in the morning, by subcutaneous injection for 48 weeks. | Biological | Thymosin alpha 1 |
| RibavirinAlso: CopegusRibavirin 1000 mg (<75 kg) or 1200 mg (>75 kg) daily with food divided in two doses orally for 48 weeks | Drug | Placebo, Thymosin alpha 1 |
| PEGinterferon alfa2aAlso: Pegasys180 mcg, once weekly in the evening, by subcutaneous injection for 48 weeks | Biological | Placebo, Thymosin alpha 1 |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Sustained Virological Response (SVR)
Time frame: Week 72
The proportion of patients who were HCV RNA negative at the end of observation period.
4 secondary outcomes
Sustained Biochemical Response (SBR)
Time frame: Week 72
End of Treatment Biochemical Response (EBR)
Time frame: Week 48
End of Treatment Virological Response [EVR]
Time frame: Week 48
Safety
Time frame: During the treatment period (up to 48 weeks) and the follow-up period (up to 24 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2010.
- Derived from this study: PubMed 22233415Ciancio 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Rizzetto, MD principal investigator
Dipartimento Medico Chirurgico delle Malattie dell'Apparato Digerente e della Nutrizione, Azienda Ospedaliera S Giovanni Battista, Corso Bramante 88, Turin, Italy
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Thymosin alpha 1, Ribavirin and PEGinterferon alfa2a in people with Chronic Hepatitis C, run by sigma-tau i.f.r. S.p.A. at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy, France, Germany, Greece, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sustained Virological Response (SVR) (time frame: Week 72). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01178996, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2010.