Nucleos(t)ide withdrawal in Hepatitis B virus infection (NUC-B)
| ISRCTN | ISRCTN84346215 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84346215 |
| Secondary identifying numbers | 32555 |
- Submission date
- 07/11/2016
- Registration date
- 11/11/2016
- Last edited
- 31/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
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 August 2024
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Mariam Habib
m.habib@imperial.ac.uk
Contact information
Scientific
Imperial Clinical Trials Unit
Stadium House
68 Wood Lane
London
W12 7RH
United Kingdom
| Phone | +44 (0)207 594 8859 |
|---|---|
| m.habib@imperial.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Nucleos(t)ide withdrawal in HBeAg negative hepatitis B virus infection to promote HBsAg clearance (NUC-B) |
| 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(s) | London - Central Research Ethics Committee, 26/08/2016, ref: 16/LO/1318 |
| 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 |
| Primary outcome measure | 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 study start date | 01/06/2016 |
| Overall study end date | 31/08/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 240; UK Sample Size: 240 |
| 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 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 | 30/07/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
10th Floor
QEQM Building
London
W2 1NY
United Kingdom
Denmark Hill
London
SE5 9RS
United Kingdom
London
E1 1BB
United Kingdom
Department of Gastroentrology
Nottingham
NG7 2UH
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
Birmingham
B15 2TH
United Kingdom
Leeds
LS9 7TF
United Kingdom
Manchester
M13 9WL
United Kingdom
High Heaton
Newcastle-Upon-Tyne
NE7 7DN
United Kingdom
Sponsor information
University/education
Exhibition Road
London
SW7 2AZ
England
United Kingdom
"ROR" |
https://ror.org/041kmwe10 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 28/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
31/01/2025: The following changes were made to the trial record:
1. The overall end date was changed from 30/11/2021 to 31/08/2024.
2. The intention to publish date was changed from 30/11/2022 to 28/02/2025.
3. The plain English summary was updated to reflect these changes.
20/09/2021: Internal review.
23/07/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/05/2018 to 30/07/2018.
2. The overall trial end date was changed from 30/01/2021 to 30/11/2021.
