Pegasys Plus Entecavir Versus Entecavir Versus Pegasys for Hepatitis B e Antigen-Negative Chronic Hepatitis B
NCT ID: NCT01925820
Last Updated: 2014-12-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE4
540 participants
INTERVENTIONAL
2013-01-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Although the best treatment choice for CHB is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C or human immunodeficiency virus (HIV) infection. A major advancement in treating hepatitis C or HIV infection has been the development of combination therapy. Combination therapy has ever been investigated in patients with CHB, but again the optimal strategy remains to be identified. Entecavir, a carbocyclic deoxyguanosine NA, is one of the most potent anti-HBV agents ever discovered. In addition, the 6-year drug resistance rate is 1.2% in selected lamivudine-naïve cohorts. Pegylated interferon alfa-2a possesses both antiviral and immunomodulatory effects. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alfa in around 30-44% of these patients. Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV or Peg-IFN alfa-2a alone is not clarified. A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with CHB. In this proposal, the investigators thus hypothesize that the efficacy by using combination therapy with Peg-IFN alfa-2a plus prolonged ETV is superior to that by using ETV or Peg-IFN alfa-2a alone in that Peg-IFN may restore host immunity against HBV and prolonged ETV can maximize viral suppression.
The objective of this clinical trial is to evaluate the efficacy of the combination of Peg-IFN alfa-2a at a dose of 180 mcg administered subcutaneously per week and ETV 0.5 mg daily for 48 weeks followed by ETV 0.5 mg daily monotherapy for an additional 96 weeks versus ETV 0.5 mg daily monotherapy for 144 weeks or Peg-IFN alfa-2a 180 mcg per week for 48 weeks in patients with HBeAg-negative CHB. It will be an open-label, randomized, comparative, multi-center clinical trial. The recruited patients will be equally randomized into three treatment groups. Treatment-free follow-up period will be 48 weeks in both groups of patients. The primary parameter is the "Simultaneous achievement of HBsAg titer below 100 IU/ml and HBV DNA below 300 IU/ml at 144 weeks after start of treatment", by an intention-to-treat analysis. Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1, 2 and 3.
The investigators anticipate that the rate of HBsAg \<100 IU/mL plus HBV DNA \<300 IU/mL at 3 years of the study period will be 30% for patients receiving Peg-IFN therapy and increased to be 45% for patients receiving Peg-IFN plus entecavir therapy. With a 5% nominal significance level (two-sided), 163 patients per group under a 1:1:1 ratio will provide 80% power to detect a difference of 15% in treatment response rates between group I and III. Because this will be a 4-year study for each patient, the investigators thus anticipate that the dropout rate may be as high as 10%. Accordingly, a total of 540 (180x3) patients will be recruited, in order to account for a dropout rate of up to10%.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm 1
180 mcg Peg-IFN alfa-2a (Pegasys) once a week for 48 weeks. Entecavir daily will also be administered concurrently for 48 weeks and then given as monotherapy for an additional 96 weeks
Pegasys&Entecavir
180 mcg Peg-IFN alfa-2a (Pegasys) once a week for 48 weeks. Entecavir daily will also be administered concurrently for 48 weeks and then given as monotherapy for an additional 96 weeks.
Arm 2
Entecavir daily for 144 weeks.
Pegasys&Entecavir
180 mcg Peg-IFN alfa-2a (Pegasys) once a week for 48 weeks. Entecavir daily will also be administered concurrently for 48 weeks and then given as monotherapy for an additional 96 weeks.
Arm 3
180 mcg Peg-IFN alfa-2a once a week for 48 weeks
Pegasys&Entecavir
180 mcg Peg-IFN alfa-2a (Pegasys) once a week for 48 weeks. Entecavir daily will also be administered concurrently for 48 weeks and then given as monotherapy for an additional 96 weeks.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pegasys&Entecavir
180 mcg Peg-IFN alfa-2a (Pegasys) once a week for 48 weeks. Entecavir daily will also be administered concurrently for 48 weeks and then given as monotherapy for an additional 96 weeks.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Positive serum HBV DNA within 3 months prior to entry (HBV DNA \>10,000 copies/mL or 2000 IU/mL).
* Negative serum HBeAg within 3 months prior to entry.
* Documented presence of abnormal alanine aminotransferase (ALT) twice within 6 months prior to entry, at least 3 months apart (2 to 10 folds above the upper normal level).
* Naïve to interferon, lamivudine, and telbivudine; but patients ever receiving adefovir, tenofovir or entecavir could be enrolled, only if they have been discontinued for more than 3 months.
2. Compensated liver disease with the following minimum hematological and serum biochemical criteria:
* Hemoglobin values of 12 gm/dL for both genders
* WBC 3,000/mm3
* Neutrophil count 1,500/ mm3
* Platelets 100,000/ mm3
* PT prolong 3 sec, INR 1.2
* 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)
* Hemoglobin A1C 8.5% for diabetic patients (whether on medication and/or controlled with diet)
Exclusion Criteria
5. Negative antibody to human immunodeficiency virus (anti-HIV)
6. Alfa-fetoprotein within normal range (obtained within the previous year, or if elevated and \<100 ng/ml, then a negative ultrasound for hepatocellular carcinoma within prior 3 months is required.)
7. Subject must be willing to give written informed consent and be able to adhere to dose and visit schedules \*Patients with well compensated liver cirrhosis (Child-Pugh A), in the absence of splenomegaly (by abdominal ultrasonography) and varices (if patients ever received upper GI endoscope),could be enrolled.
1. Women who are pregnant or nursing.
2. Prior treatment for hepatitis with any interferon, lamivudine, telbivudine, or other investigational agents.
3. Prior treatment for hepatitis with immunomodulatory drug within previous 2 years.
4. Suspected hypersensitivity to interferon.
5. Have evidence of cirrhosis with the presence of splenomegaly or varices, or evidence of decompensated cirrhosis.
6. History of severe psychiatric disease, especially depression.
7. Concurrent malignancies (including hepatocellular carcinoma).
8. Unstable or significant cardiovascular diseases (e.g., angina, congestive heart failure,recent myocardial infarction, severe hypertension or significant arrhythmia; subjects with ECG showing clinically significant abnormalities).
9. Prolonged exposure to known hepatotoxins such as alcohol or drugs
10. History of thyroid disease poorly controlled on prescribed medication
11. Poorly controlled diabetes mellitus
12. Have suspected or confirmed significant hepatic disease from an etiology other than HBV (e.g., alcohol, autoimmune disease etc.)
13. Patients co-infected with hepatitis C, hepatitis D and /or HIV
14. Severe renal disease or myeloid dysfunction
15. History of organ transplantation other than cornea and hair transplant
16. Any medical condition requiring, or likely to require during the course of the study,chronic systemic administration of steroids
17. Any other condition which in the opinion of the investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in and completing the protocol.
20 Years
70 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Roche Pharma AG
INDUSTRY
National Taiwan University Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Pei-Jer Chen, M.D., Ph.D.
Role: PRINCIPAL_INVESTIGATOR
National Taiwan University Hospital Department of Internal Medicine
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Taiwan University Hospital Department of Internal Medicine
Taipei, , Taiwan
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
201205003MPC
Identifier Type: -
Identifier Source: org_study_id