Terminator 2 Register

Termination of Nucleos(t)Ide Analogue Therapy of HBeAg Negative Chronic Hepatitis B - 2nd Register Study

All patients with chronic HBeAg negative hepatitis B treated with nucleos(t)ide analogues, who discontinue treatment based in the criteria outlined in the EASL hepatitis B guidelines shall be included in the present study. The aim is to evaluate the clinical outcome (virological relapse, HBsAg decline) and associated virological and immunological parameters.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis B, HBeAg Negative

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Markus Cornberg, MD, Prof; Phone Number: 0049-511-532-6821; Email: cornberg.markus@mh-hannover.de
• Study Contact Backup: Name: Christoph Höner zu Siederdissen, MD; Email: hoenerzusiederdissen.christoph@mh-hannover.de

Study Locations

• Germany
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Recruiting
      • Hannover Medical School
      • Contact: Christoph Höner zu Siederdissen, MD; Email: hoenerzusiederdissen.christoph@mh-hannover.de
      • Contact: Markus Cornberg, MD; Email: cornberg.markus@mh-hannover.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. Non-cirrhotic male and female patients with chronic hepatitis B virus infection documented by detectable HBsAg.
2. Age > 18 years
3. ongoing antiviral therapy with Entecavir or Tenofovir (TDF)
4. At least 3 years HBV-DNA < 20 IU/ml (=100 copies/ml)
5. HBeAg negative

Description

Inclusion Criteria:

1. Male and female patients with chronic hepatitis B virus infection documented by detectable HBsAg.
2. Age > 18 years
3. Ongoing antiviral therapy with Entecavir or Tenofovir (TDF)
4. At least 3 years HBV-DNA < 20 IU/ml (=100 copies/ml)
5. HBeAg negative
6. Willingness to give written informed consent and willingness to participate and to comply with the protocol.

Exclusion Criteria:

1. HIV infection, persistent HDV-infection, persistent HCV infection
2. History or other evidence of a medical condition associated with chronic liver disease other than HBV associated (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
3. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
4. Patients with advanced liver fibrosis and liver cirrhosis (fibroscan >10.0 kPa)
5. Patients with hepatocellular carcinoma
6. History of major organ transplantation or other immunosuppressive conditions
7. History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study

8. History of any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 12 months prior to cessation of antiviral therapy or the expectation that such treatment will be needed at any time during the study

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Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBsAg	HBsAg Change > 1 log 48 weeks after stopping NA	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological relapse	HBV DNA > 2,000 IU/ml	at every visit up to 96 weeks
Biochemical relapse	ALT > 2 x upper limit of normal	at every visit up to 96 weeks
Retreatment	Retreatment until week 48 according to current EASL guidelines	at every visit up to 48 weeks
Negativity for HBsAg	HBsAg negative until week 96 of follow-up	at every visit up to 96 weeks
timepoint of relapse	timepoint of relapse	at every visit up to 96 weeks
T cell response	> 3x change of T cell responses from baseline after in vitro culture with HBV specific peptides	at every visit up to 96 weeks
Cytokine response	> 3x change of cytokines from baseline measured by ELISA and Multiplex assay	at every visit up to 96 weeks
Chance in HBcrAg	Chance in HBcrAg (U/mL)	at every visit up to 96 weeks
Change in HBV RNA	Chance in HBV RNA (U/mL)	at every visit up to 96 weeks

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: German Center for Infection Research

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: June 19, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): February 25, 2019
• Last Update Submitted That Met QC Criteria: February 22, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No