Condition category
Infections and Infestations
Date applied
07/11/2016
Date assigned
11/11/2016
Last edited
11/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Hepatitis B is a type of liver disease, which is caused by the hepatitis C virus (HBV). It can present as either a severe infection with a short duration (acute) or a persistant long term infection (chronic). If a person has a chronic HBV infection, over time the virus causes the liver to become irreversibly scarred (cirrhosis), eventually leading to liver failure. There are two main drug treatments available for treating a chronic HBV infection: interferons or nucleoside/nucleotide analogues. Interferons can have a lot of unpleasant side effects and rarely results in a cure so most patients choose to be treated with nucleoside/nucleotide analogues. Although these daily tablets have no side effects, most people using this treatment will need to continue taking them for the rest of their life. There is evidence from a recent study that if treatment with nucleoside/nucleotide analogues is stopped after a few years of treatment, some patients may be able to eliminate the virus. The aim of this study is to confirm the findings from this earlier study by seeing if stopping nucleoside/nucleotide analogue treatment can be safely stopped and lead to a cure.

Who can participate?
Adults with a long-term Hepatitis B infection who have been undergoing treatment with nucleoside/nucleotide analogues for less than 3 years.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group stop their nucleoside/nucleotide analogue treatment at the start of the study. Those in the second group stop their nucleoside/nucleotide analogue treatment at the start of the study for four weeks, before starting a course of interferon weekly injections for 16 weeks. After this, all treatment is stopped. Participants in both groups attend the clinic at regular intervals over the next three years and provide blood samples to test for signs of HBV.

What are the possible benefits and risks of participating?
There is a chance that stopping nucleoside/nucleotide analogue treatment (with or without interferon treatment) may allow the patient to be cured. There is a risk that participants may experience withdrawal symptoms when stopping their treatment or that they experience a worsening of their hepatitis (hepatitis flare) as the virus starts to replicate again.

Where is the study run from?
Ten NHS hospitals in England (UK)

When is the study starting and how long is it expected to run for?
June 2016 to January 2021

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Mariam Habib
m.habib@imperial.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mariam Habib

ORCID ID

Contact details

Imperial Clinical Trials Unit
Stadium House
68 Wood Lane
London
W12 7RH
United Kingdom
+44 207 594 8859
m.habib@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

32555

Study information

Scientific title

Nucleos(t)ide withdrawal in HBeAg negative hepatitis B virus infection to promote HBsAg clearance (NUC-B)

Acronym

Study hypothesis

The aim of this trial is to explore whether finite treatment with nucleos(t)ide analogues is feasible in patients with HBeAg (Hepatitis B ‘e’ antigen) negative chronic HBV (Hepatitis B Virus) infection.

Ethics approval

London - Central Research Ethics Committee, 26/08/2016, ref: 16/LO/1318

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Hepatology, Primary sub-specialty: Hepatology; UKCRC code/ Disease: Infection/ Viral hepatitis

Intervention

Patients will be electronically randomised using the InForm eCRF online custom built database to the two management arms in equal proportions using variable block sizes.

Control Arm: Patients will discontinue their nucleos(t)ide analogue treatment at baseline and be followed up for 3 years from randomisation.

Interferon Arm: Patients will discontinue their nucleos(t)ide analogue treatment at randomisation. No treatment will be given for 4 weeks, and then (i.e after the 4 week gap) patients will start pegylated interferon 180 mcg 2a and continue taking it weekly for a total of 16 weeks. They will then stop ALL treatment and be followed up for 3 years from randomisation.

During the follow-up the patients are required to attend the clinic at specified intervals so that their safety can be monitored throughout the study. At each of the visits, patients will have their vital signs checked and give blood samples. The blood samples will be used to measure levels of certain blood chemicals and thus evaluate the patient’s liver function, the levels of HBV in the their body and their body’s ongoing response to the HBV infection. The laboratory tests will allow us to evaluate the effects, on both the patient and the HBV levels in their body, of withdrawal from treatment and/or introduction of interferon treatment.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

HBsAg (Hepatitis B surface antigen) is measured using standard laboratory ELISA assays at baseline and 3 years.

Secondary outcome measures

1. Efficacy is assessed at various timepoints after randomisation using various laboratory evaluations including immunology, virology and hepatology assessments. Specifically looking at the following:
1.1. The proportion of patients who achieve HBsAg loss who also have undetectable HBV DNA
1.2. The proportion of patients in each group who become inactive HBV carriers; i.e. achieve a sustained virological response (HBV DNA < 2000 IU/ml & normal ALT values) at 3 years
1.3. Magnitude of reduction in quantitative HBsAg levels at 1, 6, 12, 24 and 36 months
1.4. Magnitude of changes in antiviral T cells response at 1, 5, 6, 12, 24 and 36 months
1.5. Magnitude of changes in NK cells response at 1, 5, 6, 12, 24 and 36 months
2. Safety is assessed at various timepoints after randomisation using various laboratory evaluations. Specifically looking at the following:
2.1. The proportion of patients who achieve HBsAg loss who also have undetectable HBV DNA
2.2. The proportion of patients in each group who become inactive HBV carriers; i.e. achieve a sustained virological response (HBV DNA < 2000 IU/ml & normal ALT values) at 3 years
2.3. Magnitude of reduction in quantitative HBsAg levels at 1, 6, 12, 24 and 36 months
2.4. Magnitude of changes in antiviral T cells response at 1, 5, 6, 12, 24 and 36 months
2.5. Magnitude of changes in NK cells response at 1, 5, 6, 12, 24 and 36 months

Overall trial start date

01/06/2016

Overall trial end date

30/01/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 years and over
2. Chronic HBV infection
3. HBeAg negative
4. Nucleos(t)ide analogues treatment for ≥3 years
5. HBV DNA < 400 IU/ml ≥2 years
6. Informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 240; UK Sample Size: 240

Participant exclusion criteria

1. Cirrhosis at any time
2. HBeAg to anti-HBe seroconversion within the last 3 years
3. Interferon use in the last 3 years
4. Contraindications to interferon use
5. Participation in HBV-specific therapeutic vaccine studies within 12 months
6. HCV, HDV or HIV co-infection
7. Immunosuppressant use
8. Clinically significant comorbidities that, in the opinion of the investigator, render the patient unsuitable

Recruitment start date

30/11/2016

Recruitment end date

30/05/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St Mary’s Hospital
Department of Hepatology 10th Floor QEQM Building
London
W2 1NY
United Kingdom

Trial participating centre

Kings College Hospital
Institute of Liver Studies Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

The Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Nottingham Hospital
QMC Campus Department of Gastroentrology
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Royal Free Hospital
Liver Services Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

St George's Hospital
Blackshaw Road Tooting
London
SW17 0QT
United Kingdom

Trial participating centre

Queen Elizabeth Medical Centre
Edgbaston
Birmingham
B15 2TH
United Kingdom

Trial participating centre

St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road High Heaton
Newcastle-Upon-Tyne
NE7 7DN
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

Exhibition Road
London
SW7 2AZ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Results will be disseminated at scientific meetings and through publications in relevant scientific journals.

IPD Sharing plan:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

30/11/2022

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes