A multicentre randomized controlled trial evaluating the rate of sustained remission and the safety when stopping nucleos(t)ide analogue treatment in non-cirrhotic HBeAg-negative chronic Hepatitis B patients with long-term virologic response

Not Applicable

Conditions: MedDRA - chronic hepatitis B
B18
Chronic viral hepatitis

Registration Number: DRKS00006240

Lead Sponsor: niversität Leipzig

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 166

Inclusion Criteria

1. HBeAg negative chronic hepatitis B (HBsAg positive)
2. Age = 18 years, male or female
3. Continuous nucleoside or nucleotide analogue therapy with either mono or combination therapy with adefovir dipivoxil (ADV), lamivudine (LMV), telbivudine (LdT), entecavir (ETV) or tenofovir disoproxil fumarate (TDF) for at least 4 years prior to screening.
Of note, as in previous observation the rates of HBsAg loss in HBeAg negative patients were comparable during treatment with all the mentioned drugs (Figure 3) we anticipate that the different drug regimes do not represent a factor influencing the response rates after treatment cessation in this trial. However, randomisation will be stratified with respect to the kind of previous therapy (see 8.1.1)
4. Documented undetectable HBV DNA level during treatment for at least 4 years prior to screening (documented by quantification of HBV DNA at least every 6 months). Please note: In terms of this trial, we define undetectable” as below 1000 copies/mL (172 IU/mL). This comparatively high upper limit of HBV DNA levels was chosen for the definition of response to take into account that assays for HBV DNA quantification with different sensitivity are used in the participating centres.
5. Undetectable HBV DNA level at screening (analysed by central laboratory, Limbach and partners, Heidelberg)
6. Normal serum ALT levels < ULN (upper limit of normal) according to the local laboratory
7. Written informed consent

Exclusion Criteria

1. Compensated or decompensated liver cirrhosis
2. History of decompensated liver disease
3. Advanced fibrosis - defined either histologically by Scheuer score = stage 3 (within last year before screening) and/or liver stiffness = 10 kPa by elastography (Fibroscan®) or = 1.5 m/s by Acoustic Radiation Force Impulse (ARFI) (each within 6 months before screening)
4. Evidence of hepatocellular carcinoma (HCC)
5. HIV, HDV or HCV co-infection
6. Iatrogenic or disease-related immunosuppression (e.g. treatment with systemic glucocorticoids, TNFa-antibodies and other immunosuppressive drugs as well as chemotherapy or malignant disorders)
7. HBV associated extra hepatic manifestations (e.g. glomerulonephritis, panarteriitis nodosa, HBV-associated dermatosis)
8. Significant alcohol consumption (> 30 g/day for women and > 50 g/day for men)
9. Pregnant or nursing women
10. Participation in any other interventional trial
11. Suspected lack of compliance
12. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects from the trial medication on contraception)
13. Patient is incapable to give informed consent

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
sustained HBsAg loss up to week 96<br>HBsAg will be quantified in a central laboratory at every scheduled visit (Screening, Baseline, V1 up to V10) until week 96 (V10). HBsAg loss is defined as not detectable HBsAg in all subsequent assessments after HBsAg became undetectable for the first time. If at week 96, HBsAg is for the first time not detectable, a further measurement will be performed at week 108 in order to confirm the HBsAg loss

Secondary Outcome Measures