Add-on Peginterferon Following Nucleos(t)Ide Analogue Treatment

• Status: Completed
• Trial end date: 2018-05-21
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Chronic hepatitis B is caused by a virus that infects the liver. Cure is not possible but the virus can be controlled with the use of antiviral medicines,. Researchers think that adding a second antiviral medicine might help.

Objective:

• To understand how peginterferon might help treat people with chronic hepatitis B. Also, to see if peginterferon is safe to use with other antiviral medications.

Eligibility:

• Adults age 18 and older who have chronic hepatitis B and had therapy with 1 or more oral medicines for hepatitis B for at least 4 years.

Design:

• Participants will be screened with physical exam and medical history. They will complete health questionnaires about their levels of fatigue and pain. They will have blood and urine tests. They may have an eye exam.

• Participants also will have a Fibroscan. A test to measure how stiff your liver is.

• Eligible participants will have a liver biopsy. Blood will be drawn.

• Participants will be admitted to the NIH Clinical Center. They will be injected with the study drug. Then they will have a second liver biopsy. They will be discharged 24 hours later.

• Participants will give themselves study drug injections under the skin weekly for 24 weeks.

• Participants will have 5 clinic visits during the 24-week treatment period. Then they will have follow-up visits every 12 weeks for 48 weeks.

• During visits, participants may have a physical exam and medical history. They may have blood and urine tests. They may have a Fibroscan and complete questionnaires. At the final visit, they will also have a Fibroscan.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Peginterferon alfa-2a

Criteria

• INCLUSION CRITERIA:

Inclusion criteria: HBeAg positive group

1. Age >18 years and older, male or female.

2. Known serum HBsAg and HBeAg positivity at the time of screening.

3. Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry.

4. HBV DNA levels <100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study.

5. ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening

6. Written informed consent

Inclusion criteria: HBeAg negative group

1. Age >18 years and older, male or female.

2. Known serum HBsAg positivity and HBeAg negativity at the time of screening.

3. Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry.

4. HBV DNA levels <100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study

5. ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening

6. Written informed consent

EXCLUSION CRITERIA:

Exclusion criteria (for both eAg positive and negative patients)

1. Co-infection with HDV as defined by the presence of anti-HDV in serum and/or HDV antigen in the liver.

2. Co-infection with HCV as defined by the presence of HCV RNA in serum.

3. Co-infection with HIV as defined by the presence of anti-HIV in serum.

4. Decompensated liver disease as defined by serum bilirubin >2.5 mg/dL (with direct bilirubin > 0.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy.

5. Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, severe nonalcoholic steatohepatitis defined as the presence of marked ballooning injury on liver biopsy, alpha-1-anti-trypsin deficiency).

6. A history of organ transplantation or in the absence of organ transplantation, any immunosuppressive therapy requiring the use of more than 5 mg of prednisone (or its equivalent) daily.

7. Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis and diabetes mellitus with poor control, that in the opinion of the investigator may interfere with therapy.

8. Pregnancy or inability to practice contraception in patients capable of bearing or fathering children

9. Lactating women.

10. Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL.

11. eGFR < 50 ml/min, serum creatinine > 1.3 mg/dl or urine protein >1 gram/24-hours

12. History of hypersensitivity to pegylated interferon-alpha

13. Platelet count <70 mm(3)/dL

14. Hgb <12 g/dL for males and <11 g/dL for females

15. Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study.

16. History of malignancy or treatment for a malignancy within the past 3 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).

17. Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.

18. History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.

19. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study for at 1 year.

20. For subjects who interrupt therapy, documentation of a viral load >1,000 IU/ml while off therapy.