A Phase II Study to Determine the Safety and Efficacy of Interferon-gamma in Patients With Chronic Hepatitis B

October 20, 2010 updated by: Huntington Medical Research Institutes

Protocol Title: A Phase II Open-labeled Study to Determine the Safety and Preliminary Efficacy of Interferon-gamma 1b (IFN-γ 1b) in Patients With Chronic Hepatitis B Who Are HBV DNA Positive

Open-label, prospective, two part study evaluating IFN-γ 1b at a dose of 200μg by subcutaneous injection every day either alone or in combination with Adefovir dipivoxil or Adefovir dipivoxil alone at a dose of 10mg QD in patients with chronic Hepatitis B.

Study Overview

Detailed Description

After signing the informed consent potential patients will undergo a screening medical history, physical examination, and laboratory tests.

The study will consist of two parts:

  • Part A: IFN-γ 1b monotherapy
  • Part B: IFN-γ 1b combination therapy with Adefovir dipivoxil or Adefovir dipivoxil monotherapy

Patients will be enrolled sequentially into to one of three treatment groups. In Part A, ten patients will be enrolled and will receive IFN-γ 1b 200μg, administered every day by subcutaneous injection for 4 weeks. If HBV DNA is reduced by ≥ 1 log10 copies/ mL in ≥ 30% of patients the protocol will proceed to Part B.

In Part B, twenty patients will be enrolled into two cohorts (total of 10 for each cohort) and treated for four weeks. The two cohorts will be administered:

  • IFN-γ 1b 200μg, administered every day combination therapy with Adefovir dipivoxil (10mg QD) or
  • Adefovir dipivoxil (10mg QD) alone

On the initial study visit, patients will be given instruction on self injection of IFN-γ 1b (if applicable). Patients will be monitored for safety, tolerability, HBV DNA, clinical chemistries including a standard panel of liver tests and hematologies throughout the study and for the two week post-treatment observation period.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Pasadena, California, United States, 91105
        • Huntington Medical Research Institutes
        • Contact:
        • Principal Investigator:
          • Myron J Tong, PhD, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for enrollment into the study:

  1. Men or women age 18 to 75 years
  2. Chronic hepatitis B infection based on a history of positive anti-HBsAg and positive for HBV DNA and with or without elevations in liver tests (test to be repeated on screening)

Exclusion Criteria:

Patients with any of the following will be excluded from randomization:

  1. Presence of clinically evident cirrhosis including: ascites requiring active diuretic therapy, history of or therapy for hepatic encephalopathy, or history of GI variceal bleeding
  2. Platelet count < 50,000/mm3
  3. Serum ALT level > 10 times upper limit of normal
  4. Alpha-fetoprotein level ≥ 200 ng/mL or alpha-fetoprotein level between 50-200 ng/mL in association with liver ultrasound or other radiographic abnormality suspicious for hepatic neoplasm
  5. Serum creatinine level > 1.6 mg/dL
  6. Hematology outside of specified limits: neutrophil count <1000/mm3, hemoglobin <10 g/dL in males and <9 g/dL in females
  7. Unstable or uncontrolled thyroid disease
  8. Treatment with any interferon-α or nucleoside/tide analog within the previous 4 weeks
  9. Presence of clinically significant cryoglobulinemia (e.g., skin rash, arthritis, or renal insufficiency due to cryoglobuliemia)
  10. Presence or history of autoimmune hepatitis, alpha-1 anti-trypsin deficiency, hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, or sclerosing cholangitis (mild-to-moderate steatosis is acceptable)
  11. Chronic hepatitis C infection
  12. Hepatits Delta infection (HDV)
  13. Known history of HIV infection or positive HIV antibody test by Western Blot (test performed within 60 days of screening can be used to determine eligibility)
  14. A disease known to cause significant alteration in immunologic function including hematological malignancy or autoimmune disorder (e.g. rheumatoid arthritis, systemic lupus erythematosis, autoimmune thyroid disease, leukemia, lymphoma, etc)
  15. Concurrent therapy with immunosuppressive drugs or cytotoxic agents such as oral prednisone, cyclosporine, azathioprine, or chemotherapeutic agent(s) (e.g., cyclophosphamide, methotrexate, or cancer chemotherapy) or radiation therapy
  16. Behavior that suggests a significant risk of poor compliance including, but not limited to:

    1. Illicit drug abuse within the past 3 years
    2. Current or history of alcohol abuse within the past 2 years
  17. Prior treatment with IFN-γ 1b
  18. History of unstable or deteriorating cardiac disease, including but not limited to:

    1. Myocardial infarction, coronary artery bypass surgery, or angioplasty within the past 6 months
    2. Congestive heart failure requiring hospitalization within the past 6 months
    3. Uncontrolled arrhythmias
    4. Transient ischemic attacks (TIAs)
    5. Any cardiac condition that, in the opinion of the site PI, might be significantly exacerbated by flu-like symptoms associated with the administration of IFN γ 1b
  19. Preexisting (within last two years) or active psychiatric condition including severe depression, major psychoses, suicidal ideation or suicidal attempts
  20. History of (within last two years) or current neurologic or psychiatric disorder that, in the opinion of the site PI, might be exacerbated by flu-like symptoms associated with the administration of IFN γ 1b. In addition, patients with the following conditions should be excluded:

    1. History of multiple sclerosis
    2. Seizures within the past 2 years
  21. Severe or poorly controlled diabetes
  22. Pregnancy or lactation. Females of childbearing potential are required to have a negative urine pregnancy test prior to treatment and must agree to practice abstinence or prevent pregnancy by at least a barrier method of birth control for the duration of the study
  23. Hemoglobinopthies (e.g. thalassemia, sickle cell disease)
  24. Any serious or chronic disease that, in the opinion of the Principal Investigator (PI), may affect the assessment of safety or efficacy parameters. This includes, but is not limited to, patients with malignancy who are receiving chemotherapy, chronic obstructive pulmonary disease or asthma requiring maintenance oral steroids, or active kidney disease
  25. Any condition which, in the opinion of the site PI, is likely to result in the death of the patient within the next year
  26. Patients who, in the opinion of the site PI, are not suitable candidates for enrollment or would not comply with the requirements of the study
  27. Patients who have had a liver transplant
  28. Patients who have Adefovir mutations on baseline tests

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
IFN-γ 1b monotherapy: 200 micro-grams daily for 30 days
IFN-γ 1b: 200μg given SC ED = 2 vials of active drug (0.5 mL from each vial) will be mixed for a total volume of 1.0 mL per dose
Other Names:
  • Actimmune
  • Interferon gamma
  • Immune Interferon
  • IFN-gamma
Experimental: 2
IFN-γ 1b 200 micro-grams daily) combination therapy with Adefovir dipivoxil (10 mg daily) for 30 days
IFN-γ 1b: 200μg given SC ED = 2 vials of active drug (0.5 mL from each vial) will be mixed for a total volume of 1.0 mL per dose Adefovir dipivoxil: 1 tablet of 10mg given orally QD
Other Names:
  • Hepsera
  • Actimmune
  • Interferon gamma
  • Immune Interferon
  • IFN gamma
Active Comparator: 3
Adefovir dipivoxil monotherapy (10 mg QD) 30 days
Adefovir dipivoxil: 1 tablet of 10mg given orally QD
Other Names:
  • Hepsera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary objective is to evaluate the safety and tolerability of IFN-γ 1b either alone or in combination with Adefovir dipivoxil in patients with chronic Hepatitis B.
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluate the changes in serum HBV DNA concentrations following administration of Adefovir dipivoxil alone, IFN-γ 1b either alone or in combination with Adefovir dipivoxil in patients with chronic Hepatitis B.
Time Frame: 30 days
30 days
Evaluate the changes in liver tests and hematology following administration of Adefovir dipivoxil alone, IFN-γ 1b either alone or in combination with Adefovir dipivoxil in patients with chronic Hepatitis B.
Time Frame: 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Chair: Myron J Tong, Phd, MD, HMRI

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Anticipated)

August 1, 2009

Study Completion (Anticipated)

August 1, 2009

Study Registration Dates

First Submitted

September 15, 2008

First Submitted That Met QC Criteria

September 15, 2008

First Posted (Estimate)

September 16, 2008

Study Record Updates

Last Update Posted (Estimate)

October 21, 2010

Last Update Submitted That Met QC Criteria

October 20, 2010

Last Verified

September 1, 2008

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatitis B

Clinical Trials on IFN-γ 1b (Actimmune)

3
Subscribe