Chronic Hepatitis BPhase 2/3NCT00275938
Interferon Alpha 2b Plus Ribavirin for Chronic Hepatitis B
A Phase 2/3 study testing interferon alpha 2b plus ribavirin in people with Chronic Hepatitis B, run by National Taiwan University Hospital.
Trial summary
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of individuals infected with this virus has been estimated to be as high as 350 million. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- interferon alpha 2b plus ribavirin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- Oct 1998to Jun 2001
- Phase
- Phase 2/3
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adult male or female, 18 to 60 years of age chronic hepatitis B patients Patient must have documented positive serum HBsAg for a minimum of 6 months prior to entry into study.
- Patients must show evidence of HBV replication and hepatitis documented by Positive serum HBV-DNA within 3 months prior to entry (HBV-DNA > 2.5 pg/ml) Positive serum HBeAg within 3 months prior to entry. Documented presence of abnormal alanine aminotransferase (ALT) twice within 3 months prior to entry (2 to 10 fold above the upper normal level) Liver biopsy finding shows chronic hepatitis without liver cirrhosis
- Compensated liver disease with the following minimum hematological and serum biochemical criteria:
- Hemoglobin values of ≥ 12 gm/dL for both sexes
- WBC ≥ 3,000/mm3
- Neutrophil count ≥ 1,500/ mm3
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- Platelets ≥ 100,000/ mm3
- Total bilirubin ≤ 2 mg/dL
- Albumin ≥ 3.5 g/dL
- Uric acid within normal ranges
- Serum creatinine ≤ 123.76 mmol/L (≤1.4 mg/dL)
- Fasting blood sugar ≤ 6.38 mmol/L (≤115 mg/dL) for non-diabetic patients
- Hemoglobin ≤ 8.5% for diabetic patients (whether on medication and/or controlled with diet) Thyroid Stimulating Hormone (TSH), T3 \& T4 within normal limits Negative serum antibody to hepatitis C Negative antibody to human immunodeficiency virus (anti-HIV) ELISA method If the patient has a history of diabetes or hypertension, a baseline ocular examination will be required.
- Alfa-fetoprotein within normal range Written informed consent
-
Who cannot join
- Patients older than 60 years of age
- Any cause for the liver disease based on patient history or biopsy (where applicable) other than chronic hepatitis B, including but not limited to:
- Co-infection with HCV and/or HIV Hemochromatosis (iron despistion > 2 + in liver parenchyma) Alpha-1 antitrypsin deficiency Wilson's disease Renal or liver transplant patients Autoimmune hepatitis Alcoholic liver disease Obesity related liver disease Drug related liver disease Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, hepatic encephalopathy.
- Any known pre-existing medical condition that could interfere with the patient's participation in and completion of the treatment such as:
- Pre-existing psychiatric condition, especially severe epression, or a history of severe psychiatric disorder CNS trauma or active seizure disorders requiring medication. Patients with any history of cardiovascular dysfunction. Patients with any hemoglobinopathy including but not limited to thalassemia major and minor Poorly controlled diabetes mellitus Chronic pulmonary disease Immunologically mediated disease Clinical gout Sexually active females of childbearing potential must be practicing adequate contraception, Sexually active males must be practicing acceptable methods of contraception (vasectomy, condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy.
- Female patients must not breast feed during the treatment period. Patients must agree to limit the drinking of alcohol during the course or the treatment.
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- Patients receiving Chinese herbal medication during the past 3 months prior to study entry.
- Patient who did not respond to previous interferon therapy or who relapsed after a previous course of Interferon therapy.
- Patients who have been enrolled in any clinical trial for the treatment of chronic hepatitis B.
About this study
Official title: A Pilot Study Of Interferon Alpha 2b Plus Ribavirin In The Treatment Of Patients With Chronic Hepatitis B
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of individuals infected with this virus has been estimated to be as high as 350 million. Thus, in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is also needed.
Currently, there are no effective antiviral treatments to cure HBV infection in patients with chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated IFN alpha and recently entecavir. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alpha alone in around 20-44% of these patients. Nevertheless, better treatment options are still needed for the remaining >50% non-responders.
Although the best treatment choice for chronic hepatitis B is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin combination therapy, in contrast, results in much improved treatment outcomes. In our previous study and others, sustained remission rate after cessation of therapy were significantly higher in patients receiving combination therapy than those receiving IFN alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and IFN combination for the treatment of dual chronic hepatitis B and C, and the results also revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found that a significant portion (21%) of the responsive patients also cleared HBsAg. These findings imply that this combination regimen might be also effective for the control of chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study in patients with HBeAg-positive chronic hepatitis B.
Read the detailed description
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of individuals infected with this virus has been estimated to be as high as 350 million. Thus, in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is also needed.
Currently, there are no effective antiviral treatments to cure HBV infection in patients with chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated IFN alpha and recently entecavir. Conventional IFN alpha monotherapy has a narrow range of efficacy. Lamivudine, is relatively cheaper, better tolerated, and has been shown to be effective in patients with both hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B. However, virologic response to lamivudine is not as durable as that occurred spontaneously or induced by IFN treatment. In addition, prolonged lamivudine treatment is commonly associated with the emergence of drug-resistance HBV mutants accompanied by the development of breakthrough hepatitis. Adefovir is potent and has been approved for the treatment of chronic hepatitis B in several countries, but is nephrotoxic at daily doses higher than 10 mg and is still not available widely. Entecavir, a carbocyclic deoxyguanosine analog, which is active against both lamivudine- and adefovir dipivoxil-resistant HBV, is the most potent anti-HBV agent ever discovered,11 however, its long-term efficacy remains to be evaluated. Pegylated IFN alpha has recently been shown to be superior to conventional IFN alpha and lamivudine, and has also been approved for the treatment of chronic hepatitis B. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alpha alone in around 30-44% of these patients. Nevertheless, better treatment options are still needed for the remaining >50% non-responders.
Although the best treatment choice for chronic hepatitis B is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin combination therapy, in contrast, results in much improved treatment outcomes. In our previous study and others, sustained remission rate after cessation of therapy were significantly higher in patients receiving combination therapy than those receiving IFN alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and IFN combination for the treatment of dual chronic hepatitis B and C, and the results also revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found that a significant portion (21%) of the responsive patients also cleared HBsAg. These findings imply that this combination regimen might be also effective for the control of chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study in patients with HBeAg-positive chronic hepatitis B.
- Conditions
- Chronic Hepatitis B
- Being tested
- interferon alpha 2b plus ribavirin, interferon alpha 2b plus placebo
- Keywords
- hepatitis B virus, e antigen, interferon, ribavirin
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
interferon alpha 2b plus ribavirinDrug
interferon alpha 2b plus placeboDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Undetected serum HBV DNA level (i.e. less than 2.5 pg/ml) at the end of the 24-week follow-up period
Secondary outcomes (2)
HBV DNA level at the end of treatment
clearance of HBeAg and rate of ALT normalization both at the end of the 32-week treatment period and at the end of the 24-week follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2006 (estimated)
- Study startOct 1998
- Study completionJun 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 120 participants
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough
- Investigators
- Ming-Yang Lai, Professor, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00275938
- Sponsor's protocol ID
- 145R3
- Status last verified
- Jan 2006
- First submitted
- 11 Jan 2006
- Last updated
- 12 Jan 2006
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Of Interferon Alpha 2b Plus Ribavirin In The Treatment Of Patients With Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT00275938
- Acronym / sponsor ID
- 145R3
- Conditions
- Chronic Hepatitis B
- Keywords
- hepatitis B virus, e antigen, interferon, ribavirin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Schering-Plough
- Study start
- Oct 1998
- Study completion
- Jun 2001
- First posted
- 12 Jan 2006 (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.
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of individuals infected with this virus has been estimated to be as high as 350 million. Thus, in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is also needed.
Currently, there are no effective antiviral treatments to cure HBV infection in patients with chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated IFN alpha and recently entecavir. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alpha alone in around 20-44% of these patients. Nevertheless, better treatment options are still needed for the remaining >50% non-responders.
Although the best treatment choice for chronic hepatitis B is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin combination therapy, in contrast, results in much improved treatment outcomes. In our previous study and others, sustained remission rate after cessation of therapy were significantly higher in patients receiving combination therapy than those receiving IFN alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and IFN combination for the treatment of dual chronic hepatitis B and C, and the results also revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found that a significant portion (21%) of the responsive patients also cleared HBsAg. These findings imply that this combination regimen might be also effective for the control of chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study in patients with HBeAg-positive chronic hepatitis B.
Detailed description
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of individuals infected with this virus has been estimated to be as high as 350 million. Thus, in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is also needed.
Currently, there are no effective antiviral treatments to cure HBV infection in patients with chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated IFN alpha and recently entecavir. Conventional IFN alpha monotherapy has a narrow range of efficacy. Lamivudine, is relatively cheaper, better tolerated, and has been shown to be effective in patients with both hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B. However, virologic response to lamivudine is not as durable as that occurred spontaneously or induced by IFN treatment. In addition, prolonged lamivudine treatment is commonly associated with the emergence of drug-resistance HBV mutants accompanied by the development of breakthrough hepatitis. Adefovir is potent and has been approved for the treatment of chronic hepatitis B in several countries, but is nephrotoxic at daily doses higher than 10 mg and is still not available widely. Entecavir, a carbocyclic deoxyguanosine analog, which is active against both lamivudine- and adefovir dipivoxil-resistant HBV, is the most potent anti-HBV agent ever discovered,11 however, its long-term efficacy remains to be evaluated. Pegylated IFN alpha has recently been shown to be superior to conventional IFN alpha and lamivudine, and has also been approved for the treatment of chronic hepatitis B. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alpha alone in around 30-44% of these patients. Nevertheless, better treatment options are still needed for the remaining >50% non-responders.
Although the best treatment choice for chronic hepatitis B is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin combination therapy, in contrast, results in much improved treatment outcomes. In our previous study and others, sustained remission rate after cessation of therapy were significantly higher in patients receiving combination therapy than those receiving IFN alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and IFN combination for the treatment of dual chronic hepatitis B and C, and the results also revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found that a significant portion (21%) of the responsive patients also cleared HBsAg. These findings imply that this combination regimen might be also effective for the control of chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study in patients with HBeAg-positive chronic hepatitis B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Adult male or female, 18 to 60 years of age chronic hepatitis B patients Patient must have documented positive serum HBsAg for a minimum of 6 months prior to entry into study.
- Patients must show evidence of HBV replication and hepatitis documented by Positive serum HBV-DNA within 3 months prior to entry (HBV-DNA > 2.5 pg/ml) Positive serum HBeAg within 3 months prior to entry. Documented presence of abnormal alanine aminotransferase (ALT) twice within 3 months prior to entry (2 to 10 fold above the upper normal level) Liver biopsy finding shows chronic hepatitis without liver cirrhosis
- Compensated liver disease with the following minimum hematological and serum biochemical criteria:
- Hemoglobin values of ≥ 12 gm/dL for both sexes
- WBC ≥ 3,000/mm3
Key exclusion criteria (9 listed)
- Patients older than 60 years of age
- Any cause for the liver disease based on patient history or biopsy (where applicable) other than chronic hepatitis B, including but not limited to:
- Co-infection with HCV and/or HIV Hemochromatosis (iron despistion > 2 + in liver parenchyma) Alpha-1 antitrypsin deficiency Wilson's disease Renal or liver transplant patients Autoimmune hepatitis Alcoholic liver disease Obesity related liver disease Drug related liver disease Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, hepatic encephalopathy.
- Any known pre-existing medical condition that could interfere with the patient's participation in and completion of the treatment such as:
- Pre-existing psychiatric condition, especially severe epression, or a history of severe psychiatric disorder CNS trauma or active seizure disorders requiring medication. Patients with any history of cardiovascular dysfunction. Patients with any hemoglobinopathy including but not limited to thalassemia major and minor Poorly controlled diabetes mellitus Chronic pulmonary disease Immunologically mediated disease Clinical gout Sexually active females of childbearing potential must be practicing adequate contraception, Sexually active males must be practicing acceptable methods of contraception (vasectomy, condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy.
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 |
|---|---|---|
| interferon alpha 2b plus ribavirin | Drug | – |
| interferon alpha 2b plus placebo | Drug | – |
Primary outcome
Undetected serum HBV DNA level (i.e. less than 2.5 pg/ml) at the end of the 24-week follow-up period
2 secondary outcomes
HBV DNA level at the end of treatment
clearance of HBeAg and rate of ALT normalization both at the end of the 32-week treatment period and at the end of the 24-week follow-up
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 12 Jan 2006.
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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.
Ming-Yang Lai, Professor principal investigator
National Taiwan University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing interferon alpha 2b plus ribavirin in people with Chronic Hepatitis B, run by National Taiwan University Hospital.
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 15 inclusion and 9 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 12 Jan 2006. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Undetected serum HBV DNA level (i.e. less than 2.5 pg/ml) at the end of the 24-week follow-up period. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jan 2006.