Hepatitis BPhase 3NCT00114361
48 Weeks Combination Therapy for Patients With HBeAg-negative Chronic Hepatitis B Virus (HBV) Infection
A Phase 3 study testing Ribavirin and Peginterferon alpha 2a in people with Hepatitis B, run by Foundation for Liver Research at 1 site in Netherlands.
Trial summary
The purpose of this study is to investigate whether in patients with chronic HBeAg-negative hepatitis B, PEG-IFN-ribavirin combination therapy for 1 year leads to enhanced response (HBV DNA <10E4 copies/ml and normal ALT 24 weeks after treatment discontinuation) in comparison with pegylated interferon (PEG-IFN)… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Ribavirin and Peginterferon alpha 2a
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2005to Apr 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic hepatitis B
- Biopsy performed within one year prior to screening or during screening
- ALT > 1.5 x ULN
- HBeAg negative, anti-HBeAg positive
- HBV DNA > 10E5 copies/ml
- Age 18-70 years
Show all 9Show fewer
- Written informed consent
- Hepatic imaging without evidence of HCC
- All fertile males and females must be using two forms of effective contraception
Who cannot join
- Antiviral therapy against HBV within the previous 6 months; treatment with any investigational drug within 30 days of entry to this protocol
- Severe hepatitis activity as documented by ALT > 10 x ULN
- Advanced liver disease
- Pre-existent leucopenia or thrombopenia
- Co-infection with HCV,HDV or HIV
- Other acquired or inherited causes of liver disease
Show all 19Show fewer
- Alpha fetoprotein > 50 ng/ml.
- Evidence of severe renal disease
- Hyper- or hypothyroidism
- Significant cardiovascular or pulmonary dysfunction, malignancy,immunodeficiency syndromes
- Immune suppressive treatment within the previous 6 months
- Contra-indications for alpha-interferon therapy
- Pregnancy, breast-feeding
- Any medical condition requiring chronic systemic administration of steroids
- Substance alcohol or drug abuse
- Subjects with clinically significant retinal abnormalities
- Subjects with clinically significant hearing abnormalities
- Hemoglobinopathies
- Subjects with known hypersensitivity to ribavirin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)
The purpose of this study is to investigate whether in patients with chronic HBeAg-negative hepatitis B, PEG-IFN-ribavirin combination therapy for 1 year leads to enhanced response (HBV DNA <10E4 copies/ml and normal ALT 24 weeks after treatment discontinuation) in comparison with pegylated interferon (PEG-IFN) monotherapy.
Read the detailed description
Despite the introduction of newer drugs for the treatment of chronic hepatitis B, there is still no optimal treatment. Pegylated interferon alfa has proven sustained efficacy in approximately 30-40% of patients with HBeAg-positive or HBeAg-negative chronic hepatitis B. It is likely that combination therapy of pegylated interferon alfa with ribavirin in chronic hepatitis B is more effective than pegylated interferon alfa monotherapy. In chronic hepatitis C, adding ribavirin to pegylated interferon therapy doubled the sustained response rate (29% vs. 56%) and has become the standard option of treatment.
To investigate the effect of the treatment with pegylated interferon and ribavirin on the amount of inflammation and fibrosis in the liver, a liver biopsy will be performed within one year prior to screening and at the end of follow-up.
When patients with chronic hepatitis B are treated outside any study with pegylated interferon, they visit the outpatient clinic approximately every month for blood samples. So in this study the amount of blood samples taken from every patient is not increased as compared with treatment outside a study.
- Conditions
- Hepatitis B
- Being tested
- Ribavirin, Peginterferon alpha 2a
- Keywords
- HBeAg-negative, chronic, hepatitis B, viral
- Medical subject headings
- Hepatitis B, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibavirinDrug
1200 mg a day, 48 weeks
Peginterferon alpha 2aDrug
180 µg per week, 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Ribavirin + Peg IFN Receives: Drug: Ribavirin |
| 2 | Active comparator | Peg IFN + Placebo Receives: Drug: Peginterferon alpha 2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up
Measured: may 2008
Secondary outcomes (5)
ALT normalization
Measured: May 2008
HBV DNA negativity(undetectable by Taqman PCR)
Measured: May 2008
HBsAg loss from serum
Measured: May 2008
Improvement liver histology
Measured: May 2008
Combined virological, biochemical and histological response
Measured: May 2008
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2005 (estimated)
- Study startMar 2005
- Primary completionMay 2008
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Foundation for Liver Research
- Sponsor type
- University, hospital or other
- Investigators
- Harry LA Janssen, MD PhD, Principal investigator, Foundation of Liver Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00114361
- Sponsor's protocol ID
- HBV05-01
- Other IDs
- EudraCT: 2004-004736-30
- Status last verified
- Jun 2010
- First submitted
- 14 Jun 2005
- Last updated
- 22 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brakenhoff SM, de Knegt RJ, van Campenhout MJH, van der Eijk AA, Brouwer WP, van Bommel F, Boonstra A, Hansen BE, Berg T, Janssen HLA, de Man RA, Sonneveld MJ. End-of-treatment HBsAg, HBcrAg and HBV RNA predict the risk of off-treatment ALT flares in chronic hepatitis B patients. J Microbiol Immunol Infect. 2023 Feb;56(1):31-39. doi: 10.1016/j.jmii.2022.06.002. Epub 2022 Jul 2.
PubMed 35941076Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.
PubMed 35599306Brakenhoff SM, de Man RA, Boonstra A, van Campenhout MJH, de Knegt RJ, van Bommel F, van der Eijk AA, Berg T, Hansen BE, Janssen HLA, Sonneveld MJ. Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss. Aliment Pharmacol Ther. 2021 Jan;53(2):314-320. doi: 10.1111/apt.16172. Epub 2020 Nov 21.
PubMed 33222190Farag MS, van Campenhout MJH, Pfefferkorn M, Fischer J, Deichsel D, Boonstra A, van Vuuren AJ, Ferenci P, Feld JJ, Berg T, Hansen BE, van Bommel F, Janssen HLA. Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B. Clin Infect Dis. 2021 Jan 27;72(2):202-211. doi: 10.1093/cid/ciaa013.
PubMed 31912157
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)
- ClinicalTrials.gov ID
- NCT00114361
- Acronym / sponsor ID
- HBV05-01
- Conditions
- Hepatitis B
- Keywords
- HBeAg-negative, chronic, hepatitis B, viral
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- Foundation for Liver ResearchUniversity, hospital or other
- Study start
- Mar 2005
- Primary completion
- May 2008 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 15 Jun 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate whether in patients with chronic HBeAg-negative hepatitis B, PEG-IFN-ribavirin combination therapy for 1 year leads to enhanced response (HBV DNA <10E4 copies/ml and normal ALT 24 weeks after treatment discontinuation) in comparison with pegylated interferon (PEG-IFN) monotherapy.
Detailed description
Despite the introduction of newer drugs for the treatment of chronic hepatitis B, there is still no optimal treatment. Pegylated interferon alfa has proven sustained efficacy in approximately 30-40% of patients with HBeAg-positive or HBeAg-negative chronic hepatitis B. It is likely that combination therapy of pegylated interferon alfa with ribavirin in chronic hepatitis B is more effective than pegylated interferon alfa monotherapy. In chronic hepatitis C, adding ribavirin to pegylated interferon therapy doubled the sustained response rate (29% vs. 56%) and has become the standard option of treatment.
To investigate the effect of the treatment with pegylated interferon and ribavirin on the amount of inflammation and fibrosis in the liver, a liver biopsy will be performed within one year prior to screening and at the end of follow-up.
When patients with chronic hepatitis B are treated outside any study with pegylated interferon, they visit the outpatient clinic approximately every month for blood samples. So in this study the amount of blood samples taken from every patient is not increased as compared with treatment outside a study.
Study design
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: RibavirinRibavirin + Peg IFN |
| 2 | Active comparator | Drug: Peginterferon alpha 2aPeg IFN + Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Chronic hepatitis B
- Biopsy performed within one year prior to screening or during screening
- ALT > 1.5 x ULN
- HBeAg negative, anti-HBeAg positive
- HBV DNA > 10E5 copies/ml
Key exclusion criteria (19 listed)
- Antiviral therapy against HBV within the previous 6 months; treatment with any investigational drug within 30 days of entry to this protocol
- Severe hepatitis activity as documented by ALT > 10 x ULN
- Advanced liver disease
- Pre-existent leucopenia or thrombopenia
- Co-infection with HCV,HDV or HIV
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ribavirin1200 mg a day, 48 weeks | Drug | 1 |
| Peginterferon alpha 2a180 µg per week, 48 weeks | Drug | 2 |
Primary outcome
The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up
Time frame: may 2008
5 secondary outcomes
ALT normalization
Time frame: May 2008
HBV DNA negativity(undetectable by Taqman PCR)
Time frame: May 2008
HBsAg loss from serum
Time frame: May 2008
Improvement liver histology
Time frame: May 2008
Combined virological, biochemical and histological response
Time frame: May 2008
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2010.
- Derived from this study: PubMed 35941076Brakenhoff SM, de Knegt RJ, van Campenhout MJH, van der Eijk AA, Brouwer WP, van Bommel F, Boonstra A, Hansen BE, Berg T, Janssen HLA, de Man RA, Sonneveld MJ. End-of-treatment HBsAg, HBcrAg and HBV RNA predict the risk of off-treatment ALT flares in chronic hepatitis B patients. J Microbiol Immunol Infect. 2023 Feb;56(1):31-39. doi: 10.1016/j.jmii.2022.06.002. Epub 2022 Jul 2.
- Derived from this study: PubMed 35599306Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.
- Derived from this study: PubMed 33222190Brakenhoff SM, de Man RA, Boonstra A, van Campenhout MJH, de Knegt RJ, van Bommel F, van der Eijk AA, Berg T, Hansen BE, Janssen HLA, Sonneveld MJ. Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss. Aliment Pharmacol Ther. 2021 Jan;53(2):314-320. doi: 10.1111/apt.16172. Epub 2020 Nov 21.
- Derived from this study: PubMed 31912157Farag MS, van Campenhout MJH, Pfefferkorn M, Fischer J, Deichsel D, Boonstra A, van Vuuren AJ, Ferenci P, Feld JJ, Berg T, Hansen BE, van Bommel F, Janssen HLA. Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B. Clin Infect Dis. 2021 Jan 27;72(2):202-211. doi: 10.1093/cid/ciaa013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harry LA Janssen, MD PhD principal investigator
Foundation of Liver Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ribavirin and Peginterferon alpha 2a in people with Hepatitis B, run by Foundation for Liver Research at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up (time frame: may 2008). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00114361, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2010.