Hepatitis B, ChronicPhase 3NCT01095835

A Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)

A Phase 3 study testing Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg, Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg and Lamivudine (LAM) in people with Hepatitis B, Chronic, run by Hoffmann-La Roche at 22 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will compare the efficacy and safety of 2 different durations of treatment with pegylated interferon (PEG-IFN) alfa-2a in participants with Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B virus (HBV). It will also compare PEG-IFN alfa 2a treatment alone and in combination with lamivudine (LAM). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Hepatitis B, Chronic
What is being tested?: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg, Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg and Lamivudine (LAM)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 131 participants
Where: 22 sitesItaly
Study dates: Feb 2005to Jan 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

adults 18-70 years of age;
HBeAg-negative chronic hepatitis B for >/=6 months;
liver disease consistent with chronic hepatitis B.

Who cannot join

interferon-based, systemic anti-HBV, antiviral, anti-neoplastic, or immunomodulatory therapy </=12 months before first dose of study drug;
non-responders to previous interferon therapy;
co-infection with hepatitis A, C or D, or with human immunodeficiency virus (HIV);
hepatocellular cancer;
compensated (Child A, score 6) or decompensated liver disease (Child B or C).

Trial locations and contacts

22 sites in 1 country.

City, postcode or hospital

22 sites in 1 country

Italy22 sites

Study site
Bari, Apulia, 70124
Study site
Bologna, Emilia-Romagna, 40138
Study site
Brescia, Lombardy, 25125
Study site
Cagliari, Sardinia, 09042
Study site
Caserta, Campania, 81100
Study site
Castellana Grotte, Apulia, 70013
Study site
Messina, Sicily, 98124
Study site
Milan, Lombardy, 20121
Study site
Milan, Lombardy, 20122
Study site
Naples, Campania, 80131
Study site
Naples, Campania, 80135
Study site
Padova, Veneto, 35128
Study site
Palermo, Sicily, 90127
Study site
Parma, Emilia-Romagna, 43100
Study site
Pisa, Tuscany, 56124
Study site
Reggio Emilia, Emilia-Romagna, 42100
Study site
San Giovanni Rotondo, Apulia, 71013
Study site
Trieste, Friuli Venezia Giulia, 34100
Study site
Turin, Piedmont, 10126
Study site
Turin, Piedmont, 10149
Study site
Udine, Friuli Venezia Giulia, 33100
Study site
Verona, Veneto, 37134

Other trials in Italy

About this study

Official title: A Multicenter, Randomized, Controlled Study Comparing the Efficacy and Safety of 48 Weeks of 40kD Branched Pegylated Interferon Alfa-2a (PEG-IFN, RO 25-8310) Versus 96 Weeks of PEG-IFN, Alone or in Combination With 100 mg Lamivudine for 48 Weeks in Patients With HBeAg-Negative Chronic Hepatitis B

Conditions: Hepatitis B, Chronic
Being tested: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg, Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg, Lamivudine (LAM)
Medical subject headings: Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Pegylated interferon (PEG-IFN) alfa-2a, 180 mcgDrug
Also called Pegasys®
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Pegylated interferon (PEG-IFN) alfa-2a, 135 mcgDrug
Also called Pegasys®
PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.
Lamivudine (LAM)Drug
Lamivudine 100 milligrams (mg) was administered orally, daily from Week 0 to 48.

Study groups in NCT01095835
Study group	Role	What they receive
PEG-IFN48	Experimental	Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. Receives: Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN96	Experimental	Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN treatment (total 96 weeks of treatment). Receives: Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg; Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
PEG-IFN+LAM96	Experimental	Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment). Receives: Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg; Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg; Drug: Lamivudine (LAM)

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period
Combined response was defined as alanine aminotransferase (ALT) normalization plus lowering of hepatitis B virus (HBV) deoxyribo nucleic acid (DNA) levels to <20,000 copies/mL (<3,400 IU/mL) and was measured at the end of the 48-week follow-up period. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Measured: At the end of the 48-week follow-up period at Week 144

Secondary outcomes (6)

Percentage of Participants Achieving the Combined Response at the End of Treatment
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing end of treatment measurements, the next available post-treatment value was used.
Measured: At end of treatment at Week 48 or 96 depending on the study arm
Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used.
Measured: At the end of 24 weeks of follow-up at Week 120
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL
Combined response was defined here as ALT normalization plus lowering HBV-DNA levels to a cutt-off <2,000 IU/mL. In case of missing end of treatment measurements, the next available post-treatment value was used. In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Measured: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
Percentage of Participants Achieving Histological Response
Histological response was defined as an improvement by >/= 2 in the Necroinflammatory Grading and/or by an improvement by >/= 1 score in Fibrosis Staging according to Ishak. Necroinflammatory Grading ranges 0-14 and is the combined score for necrosis, range 0-10 and inflammation, range 0-4. The participant is scored for only one inflammatory condition. A higher score indicates worse condition. Fibrosis Staging according to Ishak ranges 0-6 and a higher score indicates greater fibrosis.
Measured: At the end of the 48-week follow-up period at Week 144
Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment
Measured: At the end of treatment at Week 48 or 96 depending on the study arm
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy
Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T.
Measured: At the end of the treatment period at Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2005Jan 2010

First posted30 Mar 2010 (estimated)
Study startFeb 2005
Primary completionJan 2010
Study completionJan 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 131 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01095835
Sponsor's protocol ID: ML18253
Status last verified: Mar 2016
First submitted: 26 Mar 2010
Last updated: 3 Nov 2016
Results posted: Yes, on ClinicalTrials.gov

Publications

Lampertico P, Vigano M, Di Costanzo GG, Sagnelli E, Fasano M, Di Marco V, Boninsegna S, Farci P, Fargion S, Giuberti T, Iannacone C, Regep L, Massetto B, Facchetti F, Colombo M; PegBeLiver Study Group. Randomised study comparing 48 and 96 weeks peginterferon alpha-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut. 2013 Feb;62(2):290-8. doi: 10.1136/gutjnl-2011-301430. Epub 2012 Aug 2.
PubMed 22859496

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
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All Hepatitis B, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Controlled Study Comparing the Efficacy and Safety of 48 Weeks of 40kD Branched Pegylated Interferon Alfa-2a (PEG-IFN, RO 25-8310) Versus 96 Weeks of PEG-IFN, Alone or in Combination With 100 mg Lamivudine for 48 Weeks in Patients With HBeAg-Negative Chronic Hepatitis B
ClinicalTrials.gov ID: NCT01095835
Acronym / sponsor ID: ML18253
Conditions: Hepatitis B, Chronic
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 131 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: Feb 2005
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 30 Mar 2010 (estimated)
Results: Posted 3 Nov 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
PEG-IFN48	Experimental	Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcgTreatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks.
PEG-IFN96	Experimental	Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg, Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcgTreatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN treatment (total 96 weeks of treatment).
PEG-IFN+LAM96	Experimental	Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg, Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg, Drug: Lamivudine (LAM)Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment).

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

adults 18-70 years of age;
HBeAg-negative chronic hepatitis B for >/=6 months;
liver disease consistent with chronic hepatitis B.

Key exclusion criteria (5 listed)

interferon-based, systemic anti-HBV, antiviral, anti-neoplastic, or immunomodulatory therapy </=12 months before first dose of study drug;
non-responders to previous interferon therapy;
co-infection with hepatitis A, C or D, or with human immunodeficiency virus (HIV);
hepatocellular cancer;
compensated (Child A, score 6) or decompensated liver disease (Child B or C).

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
Pegylated interferon (PEG-IFN) alfa-2a, 180 mcgAlso: Pegasys®PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.	Drug	PEG-IFN+LAM96, PEG-IFN48, PEG-IFN96
Pegylated interferon (PEG-IFN) alfa-2a, 135 mcgAlso: Pegasys®PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.	Drug	PEG-IFN+LAM96, PEG-IFN96
Lamivudine (LAM)Lamivudine 100 milligrams (mg) was administered orally, daily from Week 0 to 48.	Drug	PEG-IFN+LAM96

Primary outcome

Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period
Time frame: At the end of the 48-week follow-up period at Week 144
Combined response was defined as alanine aminotransferase (ALT) normalization plus lowering of hepatitis B virus (HBV) deoxyribo nucleic acid (DNA) levels to <20,000 copies/mL (<3,400 IU/mL) and was measured at the end of the 48-week follow-up period. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.

6 secondary outcomes

Percentage of Participants Achieving the Combined Response at the End of Treatment
Time frame: At end of treatment at Week 48 or 96 depending on the study arm
Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up
Time frame: At the end of 24 weeks of follow-up at Week 120
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL
Time frame: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
Percentage of Participants Achieving Histological Response
Time frame: At the end of the 48-week follow-up period at Week 144
Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment
Time frame: At the end of treatment at Week 48 or 96 depending on the study arm
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy
Time frame: At the end of the treatment period at Week 96

Results and safety

Results posted to the registry on 3 Nov 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PEG-IFN48	51	41
PEG-IFN96	52	40
PEG-IFN+LAM96	25	17

Primary outcome: Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period

Time frame: At the end of the 48-week follow-up period at Week 144. Number. Unit: percentage of participants

Measure	PEG-IFN48 n = 51	PEG-IFN96 n = 52	PEG-IFN+LAM96 n = 25
Value	11.8	25.0	20.0

PEG-IFN48 vs PEG-IFN96: p = 0.08, Chi-squared

Population analysed: The ITT population included all participants randomized who received at least one dose of study medication.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 48 weeks after last study treatment dose (up to Week 144). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PEG-IFN48	7 of 50 (14%)	25 of 50 (50%)	Not reported
PEG-IFN96	3 of 52 (5.8%)	27 of 52 (51.9%)	Not reported
PEG-IFN + LAM96	6 of 25 (24%)	13 of 25 (52%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22859496Lampertico P, Vigano M, Di Costanzo GG, Sagnelli E, Fasano M, Di Marco V, Boninsegna S, Farci P, Fargion S, Giuberti T, Iannacone C, Regep L, Massetto B, Facchetti F, Colombo M; PegBeLiver Study Group. Randomised study comparing 48 and 96 weeks peginterferon alpha-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut. 2013 Feb;62(2):290-8. doi: 10.1136/gutjnl-2011-301430. Epub 2012 Aug 2.

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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.

Clinical Trials study director

Hoffmann-La Roche

22 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 5 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 3 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy. 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?

Yes. Results are posted in the registry (first posted 3 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period (time frame: At the end of the 48-week follow-up period at Week 144). 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 NCT01095835, which also lists 1 linked publication.

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 3 Nov 2016.