To investigate sustained HBeAg response to peg-interferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral loadDetermine the effect of PEG-IFNa on NK cell function and…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Sustained response defined as HBV DNA level < 200 IU/ml and HBeAg loss at week
72
Frequency, phenotype and function of NK cells, Tregs and DCs.
Determination of HBV-specific T cell response
Determination of HBV and proteins in/on NK cells
Secondary outcome
not applicable
Background summary
The introduction of nucleos(t)ide analogues heralded a new era in the treatment
of chronic hepatitis B, and provided a safe, effective, and well-tolerated
alternative for interferon. Although treatment with nucleos(t)ide analogues
profoundly suppresses serum HBV DNA levels and response can be maintained over
prolonged periods with ongoing therapy, response to treatment may not be
durable in a large proportion of patients after discontinuation of therapy,
indicating the necessity of long-term, and maybe indefinite, treatment. In
contrast, antiviral potency of peginterferon (PEG-IFN) is inferior to
nucleoside analogues, but response to PEG-IFN probably is more durable in the
majority of patients due to its immunomodulatory effects. However, sustained
response can only be achieved in about 30% of PEG-IFN treated patients.
HBV specific T cell responses are ususally weak or absent in chronic HBV
patients. Treatment with a nucleoside analogue and subsequent viral decline has
shown to restore immune responsiveness in chronic HBV infected patients. Add-on
treatment with PEG-IFN can be expected to further stimulate adaptive immune
reactivity and may therefore result in higher rates of response.
Study objective
To investigate sustained HBeAg response to peg-interferon alfa-2b in chronic
HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide
analogues, thereby lowering viral load
Determine the effect of PEG-IFNa on NK cell function and induction HBV-specific
immunity in patients with relatively low viral load.
Determine whether NK cell function and HBV-specific T cell response can be
predictive for sustained off-treatment effective HBV-specific immunity
Study design
Monocenter randomized open-label pilot study with two treatment arms
Intervention
Addition of peginterferon alfa-2b therapy for 24 weeks in chronic hepatitis B
patients treated with nucleos(t)ide analogues
Study burden and risks
Patients will be treated with peginterferon alfa-2b, an antiviral agent with
many side effects. As a consequence, blood will be drawn more frequently (every
4 weeks during peginterferon treatment vs. every twelve weeks during
nucleos(t)ide analogue monotherapy) to monitor for side effects during
peginterferon treatment. Normally, a venapuncture can give the patient a
sensation of minor pain and cause a small swelling, bruise, and/or infection.
's Gravendijkwal 230
3015 CE Rotterdam
NL
's Gravendijkwal 230
3015 CE Rotterdam
NL
Listed location countries
Age
Inclusion criteria
· Chronic hepatitis B (HBsAg positive > 6 months)
· HBeAg positive, anti-HBe negative within one month prior to initiation of peg-interferon alfa-2b
· HBV DNA < 2000 IU/ml during nucleos(t)ide analogue treatment within one month prior to initiation of peg-interferon alfa-2b
· Compensated liver disease
· Age > 18 years
· Written informed consent
Exclusion criteria
· Treatment with any investigational drug within 30 days of entry to this protocol
· Severe hepatitis activity as documented by ALT>10 x ULN
· History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
· Pre-existent neutropenia (neutrophils <1,800/mm3) or thrombocytopenia (platelets <90,000/mm3)
· Co-infection with hepatitis C virus, hepatitis D virus or human immunodeficiency virus (HIV)
· Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson*s disease or alpha-1 antitrypsin deficiency
· Alpha fetoprotein > 50 ng/ml
· Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
· Immune suppressive treatment within the previous 6 months
· Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or PEG-interferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
· Pregnancy, breast-feeding
· Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
· Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
· Substance abuse, such as alcohol (>80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
· Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-007446-54-NL |
| CCMO | NL25927.078.08 |