Trial record 21 of 440 for:    hepatitis b | Open Studies

Pegasys Plus Entecavir Versus Entecavir Versus Pegasys for Hepatitis B e Antigen-Negative Chronic Hepatitis B

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Taiwan University Hospital
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01925820
First received: August 16, 2013
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

Currently, there are several antiviral treatments effective for suppression of viral replication but still failed to cure HBV infection in patients with chronic hepatitis B (CHB). Seven drugs have been worldwide approved for the treatment of CHB at present: conventional IFN (IFN) alfa, lamivudine (LAM), adefovir dipivoxil (ADV), pegylated IFN (Peg-IFN) alfa, entecavir (ETV), telbivudine (LdT) and tenofovir (TDF). Conventional or Peg-IFN alfa monotherapy has a narrow range of efficacy, is associated with several adverse effects and is inconvenient because of frequent injections. Oral nucleot(s)ide analogues (NA) are better tolerated; but virologic response to NA is frequently not durable and prolonged treatment is associated with the emergence of drug-resistant HBV mutants.

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%.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Pegasys&Entecavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pegasys Plus Entecavir Versus Entecavir Versus Pegasys for Hepatitis B e Antigen-Negative Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Simultaneous achievement of HBsAg below 100 IU/mL and HBV DNA<300 IU/mL [ Time Frame: at 144 weeks after start of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • serum HBV DNA <2000 IU/mL,HBsAg <1000 IU/mL,ALT normalization,HBsAg loss,entecavir resistance, HBsAg seroconversion,Fibrosis stages [ Time Frame: At 144 weeks after the start of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 540
Study Start Date: January 2013
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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 Name: No other names
Active Comparator: Arm 2
Entecavir daily for 144 weeks.
Drug: 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 Name: No other names
Active Comparator: Arm 3
180 mcg Peg-IFN alfa-2a once a week for 48 weeks
Drug: 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 Name: No other names

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult male or female, 20 to 70 years of age 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 >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)
  3. Thyroid stimulating hormone (TSH), within normal ranges (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other.inclusion/exclusion criteria are met)
  4. Negative serum antibody to hepatitis C (anti-HCV) and hepatitis D (anti-HDV)
  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.

Exclusion Criteria:

  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.
  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: NCT01925820

Contacts
Contact: Pei-Jer Chen, M.D., Ph.D. 886-2-23123456 ext 67072 peijerchen@ntu.edu.tw
Contact: Chun-Jer Liu, M.D., Ph.D. 886-2-23123456 ext 67503 cjliu@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Department of Internal Medicine Recruiting
Taipei, Taiwan
Contact: Pei-Jer Chen    886-2-23123456 ext 67072    peijerchen@ntu.edu.tw   
Principal Investigator: Pei-Jer Chen         
Sponsors and Collaborators
National Taiwan University Hospital
Roche Pharma AG
Investigators
Principal Investigator: Pei-Jer Chen, M.D., Ph.D. National Taiwan University Hospital Department of Internal Medicine
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01925820     History of Changes
Other Study ID Numbers: 201205003MPC
Study First Received: August 16, 2013
Last Updated: April 16, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Hepatitis B,Entecavir,Pegylated IFN

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Peginterferon alfa-2a
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014