A Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01095835
Collaborator
(none)
131
22
3
59
6
0.1
Study Details
Study Description
Brief 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). The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
131 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date
:
Feb 1, 2005
Actual Primary Completion Date
:
Jan 1, 2010
Actual Study Completion Date
:
Jan 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PEG-IFN48 Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. |
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Other Names:
|
| Experimental: PEG-IFN96 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). |
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Other Names:
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.
Other Names:
|
| Experimental: PEG-IFN+LAM96 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). |
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Other Names:
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.
Other Names:
Drug: Lamivudine (LAM)
Lamivudine 100 milligrams (mg) was administered orally, daily from Week 0 to 48.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period [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.
Secondary Outcome Measures
- Percentage of Participants Achieving the Combined Response at the End of Treatment [At end of treatment at Week 48 or 96 depending on the study arm]
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.
- Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up [At the end of 24 weeks of follow-up at Week 120]
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.
- Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL [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]
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.
- Percentage of Participants Achieving Histological Response [At the end of the 48-week follow-up period at Week 144]
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.
- Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment [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 [At the end of the treatment period at Week 96]
Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T.
Other Outcome Measures
- Percentage of Participants With ALT Normalization [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 With HBV-DNA Lowering to <3,400 IU/mL and to < 2,000 IU/mL [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 With HBV-DNA Below Limit of Quantification [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]
HBV-DNA limit < 6 IU/mL was defined as below quantification.
- Percentage of Participants With Loss of Hepatitis B Surface Antigen (HbsAg) and Hepatitis B Surface Antibodies (Anti-HBs) Seroconversion [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]
This outcome measure presents percentage of participants with a combined response of HBsAg < 5 IU/mL and anti-HBs positive. Positive anti-HBs represents antibodies produced against Hepatitis B Surface Antigen (HBsAg) and is an indication of recovery and immunity from HBV infection.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adults 18-70 years of age;
-
HBeAg-negative chronic hepatitis B for >/=6 months;
-
liver disease consistent with chronic hepatitis B.
Exclusion Criteria:
-
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Caserta | Campania | Italy | 81100 | |
| 2 | Napoli | Campania | Italy | 80131 | |
| 3 | Napoli | Campania | Italy | 80135 | |
| 4 | Bologna | Emilia-Romagna | Italy | 40138 | |
| 5 | Parma | Emilia-Romagna | Italy | 43100 | |
| 6 | Reggio Emilia | Emilia-Romagna | Italy | 42100 | |
| 7 | Trieste | Friuli-Venezia Giulia | Italy | 34100 | |
| 8 | Udine | Friuli-Venezia Giulia | Italy | 33100 | |
| 9 | Brescia | Lombardia | Italy | 25125 | |
| 10 | Milano | Lombardia | Italy | 20121 | |
| 11 | Milano | Lombardia | Italy | 20122 | |
| 12 | Torino | Piemonte | Italy | 10126 | |
| 13 | Torino | Piemonte | Italy | 10149 | |
| 14 | Bari | Puglia | Italy | 70124 | |
| 15 | Castellana Grotte | Puglia | Italy | 70013 | |
| 16 | San Giovanni Rotondo | Puglia | Italy | 71013 | |
| 17 | Cagliari | Sardegna | Italy | 09042 | |
| 18 | Messina | Sicilia | Italy | 98124 | |
| 19 | Palermo | Sicilia | Italy | 90127 | |
| 20 | Pisa | Toscana | Italy | 56124 | |
| 21 | Padova | Veneto | Italy | 35128 | |
| 22 | Verona | Veneto | Italy | 37134 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01095835
Other Study ID Numbers:
- ML18253
First Posted:
Mar 30, 2010
Last Update Posted:
Nov 3, 2016
Last Verified:
Mar 1, 2016
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The Intent-to-Treat (ITT) population (n=128) included all participants randomized who received at least one dose of study medication. Three enrolled participants (total enrolled n=131) did not receive any study medication and were therefore excluded from the ITT population.The ITT population is reported in the Participant Flow. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with pegylated interferon (PEG-IFN) alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 milligrams (mg) of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Period Title: Overall Study | |||
| STARTED | 51 | 52 | 25 |
| COMPLETED | 41 | 40 | 17 |
| NOT COMPLETED | 10 | 12 | 8 |
Baseline Characteristics
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 | Total |
|---|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. | Total of all reporting groups |
| Overall Participants | 51 | 52 | 25 | 128 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
45.1
(10.2)
|
44.1
(10.4)
|
45.6
(8.6)
|
44.6
(9.9)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
18
35.3%
|
7
13.5%
|
7
28%
|
32
25%
|
| Male |
33
64.7%
|
45
86.5%
|
18
72%
|
96
75%
|
Outcome Measures
| Title | Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period |
|---|---|
| Description | 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. |
| Time Frame | At the end of the 48-week follow-up period at Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| Number [percentage of participants] |
11.8
23.1%
|
25.0
48.1%
|
20.0
80%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PEG-IFN48, PEG-IFN96 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.08 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Title | Percentage of Participants Achieving the Combined Response at the End of Treatment |
|---|---|
| Description | 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. |
| Time Frame | At end of treatment at Week 48 or 96 depending on the study arm |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| Number [percentage of participants] |
29.4
57.6%
|
38.5
74%
|
32.0
128%
|
| Title | Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up |
|---|---|
| Description | 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. |
| Time Frame | At the end of 24 weeks of follow-up at Week 120 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| Number [percentage of participants] |
23.5
46.1%
|
28.8
55.4%
|
24.0
96%
|
| Title | Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| End of treatment |
29.4
57.6%
|
38.5
74%
|
28.0
112%
|
| 24 weeks of follow-up |
21.6
42.4%
|
26.9
51.7%
|
20.0
80%
|
| 48 weeks of follow-up |
11.8
23.1%
|
23.1
44.4%
|
20.0
80%
|
| Title | Percentage of Participants Achieving Histological Response |
|---|---|
| Description | 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. |
| Time Frame | At the end of the 48-week follow-up period at Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| Number [percentage of participants] |
13.7
26.9%
|
5.8
11.2%
|
8.0
32%
|
| Title | Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment |
|---|---|
| Description | |
| Time Frame | At the end of treatment at Week 48 or 96 depending on the study arm |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. Baseline values are included for those participants for whom a baseline value was measured. Change from baseline values includes only those participants with both a baseline value and a value for the summarized time period. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| Baseline (n=51, 51, 25) |
9642.6
(19756.4)
|
7229.8
(6459.0)
|
8981.0
(7728.5)
|
| Change from baseline (n=44, 44, 20) |
-2801.1
(14691.2)
|
-2282.1
(6007.1)
|
-3121.2
(7128.9)
|
| Title | Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy |
|---|---|
| Description | Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T. |
| Time Frame | At the end of the treatment period at Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population for arm PEG-IFN+LAM96 included all participants randomized to PEG-IFN+LAM96 who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN+LAM96 |
|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 25 |
| Number [percentage of participants] |
0
0%
|
| Title | Percentage of Participants With ALT Normalization |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| End of treatment |
35.3
69.2%
|
40.4
77.7%
|
40.0
160%
|
| 24 weeks of follow-up |
45.1
88.4%
|
46.2
88.8%
|
40.0
160%
|
| 48 weeks of follow-up |
35.3
69.2%
|
34.6
66.5%
|
36.0
144%
|
| Title | Percentage of Participants With HBV-DNA Lowering to <3,400 IU/mL and to < 2,000 IU/mL |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| End of treatment: HBV-DNA < 3,400 IU/mL |
60.8
119.2%
|
67.3
129.4%
|
76.0
304%
|
| 24 weeks of follow-up: HBV-DNA < 3,400 IU/mL |
23.5
46.1%
|
30.8
59.2%
|
24.0
96%
|
| 48 weeks of follow-up: HBV-DNA < 3,400 IU/mL |
11.8
23.1%
|
30.8
59.2%
|
20.0
80%
|
| End of treatment: HBV-DNA < 2,000 IU/mL |
58.8
115.3%
|
67.3
129.4%
|
72.0
288%
|
| 24 weeks of follow-up: HBV-DNA < 2,000 IU/mL |
21.6
42.4%
|
28.8
55.4%
|
20.0
80%
|
| 48 weeks of follow-up: HBV-DNA < 2,000 IU/mL |
11.8
23.1%
|
28.8
55.4%
|
20.0
80%
|
| Title | Percentage of Participants With HBV-DNA Below Limit of Quantification |
|---|---|
| Description | HBV-DNA limit < 6 IU/mL was defined as below quantification. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| End of treatment |
17.6
34.5%
|
30.8
59.2%
|
24.0
96%
|
| 24 weeks of follow-up |
0.0
0%
|
7.7
14.8%
|
4.0
16%
|
| 48 weeks of follow-up |
2.0
3.9%
|
7.7
14.8%
|
8.0
32%
|
| Title | Percentage of Participants With Loss of Hepatitis B Surface Antigen (HbsAg) and Hepatitis B Surface Antibodies (Anti-HBs) Seroconversion |
|---|---|
| Description | This outcome measure presents percentage of participants with a combined response of HBsAg < 5 IU/mL and anti-HBs positive. Positive anti-HBs represents antibodies produced against Hepatitis B Surface Antigen (HBsAg) and is an indication of recovery and immunity from HBV infection. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all participants randomized who received at least one dose of study medication. |
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN+LAM96 |
|---|---|---|---|
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 mg of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. |
| Measure Participants | 51 | 52 | 25 |
| End of treatment |
2.0
3.9%
|
3.8
7.3%
|
0.0
0%
|
| 24 weeks of follow-up |
0.0
0%
|
5.8
11.2%
|
0.0
0%
|
| 48 weeks of follow-up |
0.0
0%
|
7.7
14.8%
|
0.0
0%
|
Adverse Events
| Time Frame | Up to 48 weeks after last study treatment dose (up to Week 144) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety population included all participants randomized who received at least one dose of study medication and had at least one post-baseline safety assessment. In addition to participants excluded from the Intent-to-Treat (ITT) population, one participant in the ITT population did not perform a post-baseline safety assessment, and was therefore excluded from the safety population. | |||||
| Arm/Group Title | PEG-IFN48 | PEG-IFN96 | PEG-IFN + LAM96 | |||
| Arm/Group Description | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48. | Treatment with PEG-IFN alfa-2a in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg was administered subcutaneously, once weekly from Week 0 to 48 followed by 135 mcg of PEG-IFN alfa-2a subcutaneously, once weekly from Week 49 to 96. | Treatment with PEG-IFN alfa-2a and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN alfa-2a treatment (total 96 weeks of treatment). PEG-IFN alfa-2a 180 mcg subcutaneously, once weekly and 100 milligrams (mg) of oral lamivudine daily were administered from Week 0 to 48 followed by 135 mcg of only PEG-IFN alfa-2a, subcutaneously, once weekly from Week 49 to 96. | |||
All Cause Mortality |
||||||
| PEG-IFN48 | PEG-IFN96 | PEG-IFN + LAM96 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| PEG-IFN48 | PEG-IFN96 | PEG-IFN + LAM96 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/50 (14%) | 3/52 (5.8%) | 6/25 (24%) | |||
| Blood and lymphatic system disorders | ||||||
| Iron deficiency anaemia | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| Lymphadenopathy | 0/50 (0%) | 1/52 (1.9%) | 0/25 (0%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| General disorders | ||||||
| Pyrexia | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatitis acute | 0/50 (0%) | 1/52 (1.9%) | 0/25 (0%) | |||
| Infections and infestations | ||||||
| Cytomegalovirus infection | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| Infected cyst | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Meniscus lesion | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Intervertebral disc protrusion | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
| Muscular weakness | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Colon cancer | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
| Nervous system disorders | ||||||
| Facial palsy | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| Syncope | 0/50 (0%) | 1/52 (1.9%) | 0/25 (0%) | |||
| Guillain-Barre syndrome | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Pregnancy | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Interstitial lung disease | 1/50 (2%) | 0/52 (0%) | 0/25 (0%) | |||
| Vascular disorders | ||||||
| Hypertensive crisis | 0/50 (0%) | 0/52 (0%) | 1/25 (4%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| PEG-IFN48 | PEG-IFN96 | PEG-IFN + LAM96 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 25/50 (50%) | 27/52 (51.9%) | 13/25 (52%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 5/50 (10%) | 4/52 (7.7%) | 1/25 (4%) | |||
| Leukopenia | 1/50 (2%) | 3/52 (5.8%) | 0/25 (0%) | |||
| Neutropenia | 12/50 (24%) | 9/52 (17.3%) | 3/25 (12%) | |||
| Thrombocytopenia | 6/50 (12%) | 6/52 (11.5%) | 1/25 (4%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 1/50 (2%) | 1/52 (1.9%) | 2/25 (8%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 4/50 (8%) | 4/52 (7.7%) | 3/25 (12%) | |||
| Abdominal pain upper | 2/50 (4%) | 4/52 (7.7%) | 1/25 (4%) | |||
| Diarrhoea | 0/50 (0%) | 3/52 (5.8%) | 2/25 (8%) | |||
| Dyspepsia | 1/50 (2%) | 4/52 (7.7%) | 2/25 (8%) | |||
| Nausea | 5/50 (10%) | 2/52 (3.8%) | 2/25 (8%) | |||
| General disorders | ||||||
| Asthenia | 17/50 (34%) | 19/52 (36.5%) | 11/25 (44%) | |||
| Influenza like illness | 9/50 (18%) | 10/52 (19.2%) | 4/25 (16%) | |||
| Pyrexia | 18/50 (36%) | 19/52 (36.5%) | 8/25 (32%) | |||
| Infections and infestations | ||||||
| Pharyngitis | 3/50 (6%) | 2/52 (3.8%) | 0/25 (0%) | |||
| Tooth abscess | 0/50 (0%) | 1/52 (1.9%) | 2/25 (8%) | |||
| Urinary tract infection | 3/50 (6%) | 1/52 (1.9%) | 0/25 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 2/50 (4%) | 4/52 (7.7%) | 2/25 (8%) | |||
| Blood thyroid stimulating hormone increased | 1/50 (2%) | 0/52 (0%) | 2/25 (8%) | |||
| Platelet count decreased | 0/50 (0%) | 4/52 (7.7%) | 0/25 (0%) | |||
| White blood cell count decreased | 0/50 (0%) | 3/52 (5.8%) | 1/25 (4%) | |||
| Metabolism and nutrition disorders | ||||||
| Anorexia | 2/50 (4%) | 6/52 (11.5%) | 0/25 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 6/50 (12%) | 6/52 (11.5%) | 3/25 (12%) | |||
| Back pain | 3/50 (6%) | 6/52 (11.5%) | 2/25 (8%) | |||
| Myalgia | 7/50 (14%) | 8/52 (15.4%) | 4/25 (16%) | |||
| Nervous system disorders | ||||||
| Headache | 13/50 (26%) | 8/52 (15.4%) | 7/25 (28%) | |||
| Sciatica | 1/50 (2%) | 3/52 (5.8%) | 0/25 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 4/50 (8%) | 5/52 (9.6%) | 2/25 (8%) | |||
| Insomnia | 4/50 (8%) | 0/52 (0%) | 2/25 (8%) | |||
| Irritability | 0/50 (0%) | 3/52 (5.8%) | 2/25 (8%) | |||
| Nervousness | 0/50 (0%) | 3/52 (5.8%) | 1/25 (4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 3/50 (6%) | 6/52 (11.5%) | 0/25 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 3/50 (6%) | 3/52 (5.8%) | 1/25 (4%) | |||
| Pruritus | 5/50 (10%) | 6/52 (11.5%) | 3/25 (12%) | |||
| Psoriasis | 0/50 (0%) | 3/52 (5.8%) | 0/25 (0%) | |||
| Urticaria | 1/50 (2%) | 1/52 (1.9%) | 2/25 (8%) | |||
| Vascular disorders | ||||||
| Hypertension | 1/50 (2%) | 4/52 (7.7%) | 0/25 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01095835
Other Study ID Numbers:
- ML18253
First Posted:
Mar 30, 2010
Last Update Posted:
Nov 3, 2016
Last Verified:
Mar 1, 2016