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

NCT02364336 | Completed Phase 2 Results

• 2 other identifiers: 15008215-DK-0082
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Change in Interferon-stimulated-gene (ISG) Expression

  Change in level of ISG expression before and after 1st peginterferon injection

  6 hours after first injection of peginterferon

Secondary Outcomes (4)

• Hepatitis B e Antigen (HBeAg) Loss

  End of treatment, 24 weeks, and 48 weeks

• Hepatitis B s Antigen (HBsAg) Loss

  End of treatment, 24 weeks, and 48 weeks

• Change in Natural Killer (NK) Cell Frequency

  6 hours after first injection of peginterferon and baseline

• Change in Natural Killer (NK) Cell Degranulation

  6 hours after first injection of peginterferon and baseline

Study Arms (2)

HBeAg positive

EXPERIMENTAL

Patients who have been treated with one or more nucleos(t)ides for at least 192 weeks who have known serum HBsAg and HBeAg positivity

Drug: Peginterferon alfa-2a

HBeAg negative

EXPERIMENTAL

Patients who have been treated with one or more nucleos(t)ides for at least 192 weeks who have known serum HBsAg positivity and HBeAg negativity

Drug: Peginterferon alfa-2a

Interventions

Peginterferon alfa-2a DRUG

HBeAg negative; HBeAg positive

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years and older, male or female.
• Known serum HBsAg and HBeAg positivity at the time of screening.
• 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.
• HBV DNA levels \<100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study.
• 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
• Written informed consent
• Age \>18 years and older, male or female.
• Known serum HBsAg positivity and HBeAg negativity at the time of screening.
• 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.
• HBV DNA levels \<100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study
• 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
• Written informed consent

You may not qualify if:

• Co-infection with HDV as defined by the presence of anti-HDV in serum and/or HDV antigen in the liver.
• Co-infection with HCV as defined by the presence of HCV RNA in serum.
• Co-infection with HIV as defined by the presence of anti-HIV in serum.
• 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.
• 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).
• 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.
• 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.
• Pregnancy or inability to practice contraception in patients capable of bearing or fathering children
• Lactating women.
• 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.
• eGFR \< 50 ml/min, serum creatinine \> 1.3 mg/dl or urine protein \>1 gram/24-hours
• History of hypersensitivity to pegylated interferon-alpha
• Platelet count \<70 mm(3)/dL
• Hgb \<12 g/dL for males and \<11 g/dL for females
• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Sadler AJ, Williams BR. Interferon-inducible antiviral effectors. Nat Rev Immunol. 2008 Jul;8(7):559-68. doi: 10.1038/nri2314.

  PMID: 18575461 BACKGROUND

• Ouzan D, Penaranda G, Joly H, Khiri H, Pironti A, Halfon P. Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs. J Clin Virol. 2013 Dec;58(4):713-7. doi: 10.1016/j.jcv.2013.09.020. Epub 2013 Sep 29.

  PMID: 24183313 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Marc Ghany
• Organization: NIDDK

mg228m@nih.gov

301-402-5115

Study Officials

• Marc G Ghany, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2015
• First Posted: February 18, 2015
• Study Start: February 14, 2015
• Primary Completion: May 21, 2018
• Study Completion: May 21, 2018
• Last Updated: September 4, 2019
• Results First Posted: August 28, 2019

Record last verified: 2018-05-21

Locations

US (1)