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

Phase 1

Conditions: HBeAg negative chronic Hepatitis B virus (HBV) infection
MedDRA version: 20.1Level: PTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2013-004882-15-DE

Lead Sponsor: niversität Leipzig

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 160

Inclusion Criteria

Patients must meet ALL of the following criteria:
1.HBeAg negative chronic hepatitis B since the begin of antiviral treatment and HBV-DNA >2000 IU/ml at the begin of treatment
2.HBsAg positive at screening
3.Age = 18 years, male or female
4.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)
5.Documented undetectable HBV DNA level during treatment for at least 4 years prior to screening (quantification of HBV DNA must have been performed about every 4 to 8 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.
6.Undetectable HBV DNA level at screening (analysed by central laboratory, Limbach and partners, Heidelberg)
7.Normal serum ALT levels < ULN (upper limit of normal) according to the local laboratory
8.Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160

Exclusion Criteria

Patients will be excluded for ANY ONE of the following reasons:
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.Patients with Gilbert-Meulengracht syndrome can be included in the study if other potentially underlying liver diseases causing bilirubin elevation or hemolysis can be ruled out.
9.Significant alcohol consumption (> 30 g/day for women and > 50 g/day for men)
10. Patients who work in the medical field and have patient contact.
11.Pregnant or nursing women
12.Participation in any other interventional trial
13.Suspected lack of compliance
14.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 antiviral medication on contraception).
15.Patient is incapable to give informed consent

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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