To investigate whether addition of PEG-IFN alfa-2a in HBeAg-negative chronic hepatitis B patients who are pretreated with NA enhances the degree of HBsAg decline
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome
• HBsAg decline > 1 log from baseline at week 48
Secondary outcome
Secondary outcomes
• HBsAg decline > 1 log at weeks 24 and 72
• HBsAg decline > 0.5 log at weeks 24 and 48
• HBsAg loss at weeks 48 and 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 whether addition of PEG-IFN alfa-2a in HBeAg-negative chronic
hepatitis B patients who are pretreated with NA enhances the degree of HBsAg
decline
Study design
Multicenter, international, randomized, open-label study with two treatment arms
Patients will be randomized in a 2:1 ratio to start add-on treatment with
PEG-IFN alfa-2a or continue NA monotherapy
Intervention
Addition of peginterferon alfa-2a for 48 weeks in chronich hepatitis B patients
treated with nucleos(t)ide analogues.
Study burden and risks
Patients will be treated with peginterferon alfa-2a, 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 > six months)
• HBeAg negative within six months prior to initiation of peginterferon alfa-2a
• (Peg)interferon naïve or experienced patients may both participate
• Treatment with nucleos(t)ide analogues for at least 1 year at screening
• HBV DNA < 200 IU/ml during nucleos(t)ide analogue treatment (except Telbivudine) within one month prior to initiation of peginterferon alfa-2a
• Compensated liver disease
• Age > 18 years
• Adequate contraception
• Written informed consent
Exclusion criteria
• Treatment with any investigational drug within 30 days of entry to this protocol
• Current treatment with Telbivudine
• 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 *1,500/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 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. Current methadone usage is allowed.
• 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 | EUCTR2011-002010-37-NL |
| ClinicalTrials.gov | NCT01373684 |
| CCMO | NL36655.078.11 |