To investigate sustained HBeAg response to peg-interferon alfa-2b in chronic HBeAg-positive hepatitis Bpatients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load
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
seroconversion at week 96
Secondary outcome
• Undetectable HBV-DNA (<20 IU/ml)
• HBsAg loss from serum
• HBsAg decline
• HBeAg loss from serum
• Combined response defined as the combined presence of HBV DNA
level < 200 IU/mL and HBeAg seroconversion at week 72
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
Study design
Multicenter randomized open-label study with two treatment arms
Intervention
Addition of peginterferon alfa-2b therapy for 48 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
Rotterdam 3015 CE
NL
's Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
• Chronic hepatitis B (HBsAg positive > 6 months);
• HBeAg positive, anti-HBe negative within 4 weeks prior to initiation of peginterferon alfa-2b;
• HBV DNA < 2000 IU/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months nucleos(t)ide analogue treatment, except Telbivudine;
• Compensated liver disease;
• Age >= 18 years and <= 70 years;
• Written informed consent;
Exclusion criteria
•Treatment with any investigational drug within 30 days of entry to this protocol;
•Treatment with Telbivudine;
•Severe hepatitis activity as documented by ALT >5 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 <1,500/mm3) or thrombocytopenia (platelets <90,000/mm3);
•Co-infection with hepatitis C 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 Peginterferon 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 | EUCTR2011-005607-32-NL |
| CCMO | NL39035.078.11 |