Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   44200   clinical trials with a EudraCT protocol, of which   7332   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A prospective, randomised, open-label phase IIb clinical trial assessing the effect of pegylated Interferon alfa-2a (Pegasys®) 180 µg once weekly for 48 weeks in addition to an ongoing nucelos(t)ide based treatment on quantitative HBsAg levels in patients with chronic HBeAg-negative hepatitis B

    Summary
    EudraCT number
    2011-002812-10
    Trial protocol
    DE  
    Global end of trial date
    29 Mar 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    25 Apr 2022
    First version publication date
    25 Apr 2022
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    PADD-ON
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    University Medical Center of the Johannes Gutenberg-University Mainz
    Sponsor organisation address
    Langenbeckstraße 1, Mainz, Germany, 55131
    Public contact
    Peter Galle, University Medical Center of the Johannes Gutenberg University Mainz, 0049 06131177275, peter.galle@unimedizin-mainz.de
    Scientific contact
    Peter Galle, University Medical Center of the Johannes Gutenberg University Mainz, 0049 06131177275, peter.galle@unimedizin-mainz.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Mar 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Mar 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Mar 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the trial is to investigate whether the add-on of pegylated interferon alfa-2a to a continued treatment with nucleos(t)ide analogues increases the percentage of patients who have significant decrease (≥1log10) of HBs-antigen after 48 weeks.
    Protection of trial subjects
    All patients were insured according to §40 AMG requirements. Assessment of safety and tolerability by documentation of adverse events and serious adverse events. The study fulfills all ethical standards according to the independent ethics committee (IEC), such as GCP, Federal Data Protection Law and the Declaration of Helsinki (DoH). To evaluate safety and tolerability of pegylated interferon alfa-2a when combined with tenofovir, entecavir, lamivudine, adefovir, or a combination of lamivudine or entecavir with adefovir or tenofovir the following data was collected: adverse events, vital signs, physical examination, laboratory test abnormalities, laboratory test value changes over time.
    Background therapy
    Treatment with nucleos(t)ides.
    Evidence for comparator
    Treatment with nucleos(t)ide analogues partly restores HBV directed immune responses and reduces HBsAg levels during long-term administration, with the newer drugs being more potent. Therefore the nucleos(t)ides analogues lamivudine, adefovir, entecavir, tenofovir or a combination thereof were chosen as active comparator. Due to the increased neurotoxicity of pegylated interferon alfa-2a when combined with telbivudine in a previous study, use of telbivudine was not allowed. Recent data further support that interferon treatment is even more effective in preventing HBV associated complications than high potent nucleos(t)ide analogues. This included a better prevention of cirrhosis and hepatocellular carcinoma following interferon treatment compared to an ongoing entecavir therapy. We may speculate that interferon induces a sustaining immunological surveillance of HBV infection, which positively affects long-term prognosis. Other studies have investigated an add-on interferon approach in the setting of HBeAg positive hepatitis B and provide additional evidence for this novel approach. However, stopping stable nucleos(t)ide therapy has emerged as simple and safe alternative to promote HBsAg clearance by an endogenous inflammatory flare during therapy discontinuation.
    Actual start date of recruitment
    03 Sep 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 201
    Worldwide total number of subjects
    201
    EEA total number of subjects
    201
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    199
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Recruitment and treatment of subjects were performed in 24 trial sites in Germany. Originally it was planned to replace patients who dropped out of the study before receiving any trial treatment, but further recruitment was not possible. Therefore not all randomized 170 patients could be included in the mITT population and the primary analysis.

    Pre-assignment
    Screening details
    There was an individual screening period of approximately 4 weeks. After randomisation, the treatment period took 48 weeks. Follow-up continued for another 24 weeks (72 weeks in total).

    Pre-assignment period milestones
    Number of subjects started
    201
    Number of subjects completed
    170

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Meeting any eclusion criterion: 15
    Reason: Number of subjects
    Violation of inclusion criteria: 16
    Period 1
    Period 1 title
    Treatment
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Intervention Group (Pegasys®)
    Arm description
    The group received addiotional treatment with Pegasys in the following treatment period. After the treatment period, both groups were treated with the standard therapeutic use of Nucleos(t)ides.
    Arm type
    Experimental

    Investigational medicinal product name
    pegylated interferon alfa-2a
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    In this trial the dosage and duration of Pegasys® is 180 micrograms once weekly for 48 weeks by subcutaneous administration in the abdomen or thigh which is consistent with the recommended dosage and duration for both HBeAg-positive and –negative chronic hepatitis B. Temporary interruptions of study drug(s) administration are discouraged; patients are to remain on treatment for the entire duration of the trial; and the dose of peg-IFN should not be changed during the trial, unless dose reduction is indicated because of laboratory abnormalities/adverse events (c.f. Section 4.1.8 for instructions for dose reduction). The patients must be counselled regarding the importance of not missing doses of peg-IFN.

    Arm title
    Control Group
    Arm description
    Group receiving the standard nucleos(t)ide treatment without the add-on drug [pegylated Interferon alfa-2a (Pegasys®)].
    Arm type
    Active comparator

    Investigational medicinal product name
    nucleos(t)ides
    Investigational medicinal product code
    Other name
    amivudine, adefovir, entecavir, tenofovir or one of the following combinations: lamivudine/adefovir, lamivudine/tenofovir, entecavir/adefovir or entecavir/tenof
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dose and administration according to individual summary of product characteristics.

    Number of subjects in period 1 [1]
    Intervention Group (Pegasys®) Control Group
    Started
    112
    58
    Completed
    89
    49
    Not completed
    23
    9
         Consent withdrawn by subject
    4
    4
         Other(unknown)
    6
    1
         Adverse event, non-fatal
    9
    -
         Other (Unallowed concomitant medication indicated)
    1
    -
         Lost to follow-up
    1
    4
         Other(significant change of medical condition))
    2
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Baseline values were collected before randomization after a screening procedure.
    Period 2
    Period 2 title
    Follow Up
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Intervention Group (Pegasys®)
    Arm description
    The group received addiotional treatment with Pegasys in the following treatment period. After the treatment period, both groups were treated with the standard therapeutic use of Nucleos(t)ides.
    Arm type
    Experimental

    Investigational medicinal product name
    pegylated interferon alfa-2a
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    In this trial the dosage and duration of Pegasys® is 180 micrograms once weekly for 48 weeks by subcutaneous administration in the abdomen or thigh which is consistent with the recommended dosage and duration for both HBeAg-positive and –negative chronic hepatitis B. Temporary interruptions of study drug(s) administration are discouraged; patients are to remain on treatment for the entire duration of the trial; and the dose of peg-IFN should not be changed during the trial, unless dose reduction is indicated because of laboratory abnormalities/adverse events (c.f. Section 4.1.8 for instructions for dose reduction). The patients must be counselled regarding the importance of not missing doses of peg-IFN.

    Number of subjects in period 2 [2]
    Intervention Group (Pegasys®)
    Started
    112
    Completed
    103
    Not completed
    9
         Administrative/regulatory reasons
    2
         Consent withdrawn by subject
    1
         Adverse event, non-fatal
    5
         other reasons (unspecified)
    1
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The numbers from the safety population were used for reporting.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Intervention Group (Pegasys®)
    Reporting group description
    The group received addiotional treatment with Pegasys in the following treatment period. After the treatment period, both groups were treated with the standard therapeutic use of Nucleos(t)ides.

    Reporting group title
    Control Group
    Reporting group description
    Group receiving the standard nucleos(t)ide treatment without the add-on drug [pegylated Interferon alfa-2a (Pegasys®)].

    Reporting group values
    Intervention Group (Pegasys®) Control Group Total
    Number of subjects
    112 58 170
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    43.8 ( 9.6 ) 45.1 ( 9.7 ) -
    Gender categorical
    Units: Subjects
        Female
    26 16 42
        Male
    86 42 128
    Ethnicity
    Units: Subjects
        European
    85 39 124
        Asian
    15 6 21
        African
    7 6 13
        Others
    3 4 7
        Missing
    2 3 5
    HBV DNA quant. negative ?
    Units: Subjects
        Yes
    109 54 163
        No
    1 1 2
        Missing
    2 3 5
    Anti-HBs
    Units: Subjects
        Positive
    7 2 9
        Negative
    103 53 156
        Missings
    2 3 5
    HBeAg
    Units: Subjects
        Negative
    110 55 165
        Missing
    2 3 5
    Anti-HBe
    Units: Subjects
        Positive
    96 45 141
        Negative
    11 10 21
        Missing
    5 3 8
    Anti-HBc
    Units: Subjects
        Positive
    94 48 142
        Negative
    15 7 22
        Missing
    3 3 6
    HCV
    Units: Subjects
        Negative
    110 55 165
        Missing
    2 3 5
    HDV
    Units: Subjects
        Negative
    110 55 165
        Missings
    2 3 5
    HIV
    Units: Subjects
        Negative
    109 55 164
        Missing
    3 3 6
    Is the HBV Genotype known?
    Units: Subjects
        Yes
    22 12 34
        No
    88 43 131
        Missing
    2 3 5
    HBV Genotype
    Units: Subjects
        Genotype A
    2 1 3
        Genotype C
    1 0 1
        Genotype D
    16 11 27
        Genotype E
    1 0 1
        Wildtyp
    1 0 1
        Missing
    91 46 137
    HBs antigen concentration
    Units: IU/ ml
        arithmetic mean (standard deviation)
    6547.5 ( 10326.2 ) 8434.9 ( 12660.1 ) -
    ALT
    (liver function)
    Units: U/ l
        arithmetic mean (standard deviation)
    32.4 ( 15.7 ) 34.8 ( 19.2 ) -
    AST (GOT)
    Units: U/ l
        arithmetic mean (standard deviation)
    26.6 ( 8.7 ) 28.2 ( 12.3 ) -
    Alkaline phosphatase
    Units: U/ l
        arithmetic mean (standard deviation)
    65.6 ( 18.3 ) 70.7 ( 20.2 ) -
    GGT
    Units: U/l
        arithmetic mean (standard deviation)
    26.7 ( 20.7 ) 30.3 ( 22.1 ) -
    Elastography
    Fibroscan
    Units: kPa
        arithmetic mean (standard deviation)
    6.5 ( 8.3 ) 6.9 ( 9.2 ) -
    Total bilirubin
    Units: mg/ dl
        arithmetic mean (standard deviation)
    0.6 ( 0.5 ) 0.6 ( 0.3 ) -
    Thrombocytes
    Units: /nl
        arithmetic mean (standard deviation)
    213.8 ( 56.2 ) 223.1 ( 51.1 ) -
    Albumin
    Units: g/dl
        arithmetic mean (standard deviation)
    4.3 ( 0.6 ) 4.4 ( 0.4 ) -
    PT (quick)
    clinical chemistry
    Units: percent
        arithmetic mean (standard deviation)
    96.5 ( 12.5 ) 101.2 ( 12.1 ) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Intervention Group (Pegasys®)
    Reporting group description
    The group received addiotional treatment with Pegasys in the following treatment period. After the treatment period, both groups were treated with the standard therapeutic use of Nucleos(t)ides.

    Reporting group title
    Control Group
    Reporting group description
    Group receiving the standard nucleos(t)ide treatment without the add-on drug [pegylated Interferon alfa-2a (Pegasys®)].
    Reporting group title
    Intervention Group (Pegasys®)
    Reporting group description
    The group received addiotional treatment with Pegasys in the following treatment period. After the treatment period, both groups were treated with the standard therapeutic use of Nucleos(t)ides.

    Primary: Objective response after 48 weeks

    Close Top of page
    End point title
    Objective response after 48 weeks
    End point description
    The primary endpoint was the objective response after 48 weeks of combination therapy. The response is defined as a confirmed reduction of ≥ 1 log10 in HBsAg compared to baseline. Missing values of the primary variable were carried forward in the main Analysis and the first sensitivity analysis. In the second sensitivity analysis drop-outs before week 48 were considered as non-responders, includingpatients with missing baseline values.
    End point type
    Primary
    End point timeframe
    The primary endpoint was the objective response after 48 weeks of combination therapy. Objective response is defined as confirmed reduction of ≥ 1 log10 in HBsAg compared to baseline.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: Yes, No, Missing
        confirmed reduction of ≥ 1 log10 in HBsAg
    26
    1
        no reduction
    80
    53
        missing
    4
    1
    Statistical analysis title
    Response of HBs Antigen after 48 weeks
    Comparison groups
    Intervention Group (Pegasys®) v Control Group
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Fisher exact
    Confidence interval

    Secondary: Decline of HBs antigen at week 12 (mITT)

    Close Top of page
    End point title
    Decline of HBs antigen at week 12 (mITT)
    End point description
    Differences between screening after 12 weeks compared to baseline. Modified Intention-to-treat (mITT) population was investigated.
    End point type
    Secondary
    End point timeframe
    12 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110 [1]
    55 [2]
    Units: IU/ml
        geometric mean (confidence interval 95%)
    0.7058 (0.5803 to 0.8585)
    0.9380 (0.7154 to 1.2297)
    Notes
    [1] - modified Intention-to-treat (mITT) population.
    [2] - modified Intention-to-treat (mITT) population.
    No statistical analyses for this end point

    Secondary: Decline of HBs antigen at week 24 (mITT)

    Close Top of page
    End point title
    Decline of HBs antigen at week 24 (mITT)
    End point description
    Differences between screening after 24 weeks compared to baseline. Modified Intention-to-treat (mITT) population was investigated.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: IU/ml
        geometric mean (confidence interval 95%)
    0.3694 (0.2872 to 0.4752)
    0.7995 (0.5646 to 1.1322)
    No statistical analyses for this end point

    Secondary: Patients with minimum 10% HBsAg loss at week 24 (compared to baseline)

    Close Top of page
    End point title
    Patients with minimum 10% HBsAg loss at week 24 (compared to baseline)
    End point description
    Decline of HBs antigen rate at week 24 at least 10% compared to baseline.
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: Yes, No, Missing
        Yes
    72
    21
        No
    38
    32
        Missing
    0
    2
    Statistical analysis title
    Fisher's Exact test
    Comparison groups
    Intervention Group (Pegasys®) v Control Group
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1799
    Method
    Fisher exact
    Confidence interval

    Secondary: HBsAg seroconversion detected

    Close Top of page
    End point title
    HBsAg seroconversion detected
    End point description
    HBsAg seroconversion was defined as percentage of subjects who became HBsAg negative (<10 IU/ml) and anti-HBs positive (≥10 IU/l) at least once during the observation period (baseline - EoFU).
    End point type
    Secondary
    End point timeframe
    HBsAg seroconversion defined as percentage of subjects who became HBsAg negative and anti-HBs positive during the observation period
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: Subjects
        Yes
    6
    0
        No
    104
    55
    No statistical analyses for this end point

    Secondary: Visit when HBsAg seroconversion was detected

    Close Top of page
    End point title
    Visit when HBsAg seroconversion was detected
    End point description
    Visit when HBs antigen seroconversion was first detected
    End point type
    Secondary
    End point timeframe
    During the whole study period.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: Visits
        Visit 9
    1
    0
        Visit 11
    1
    0
        Visit 13
    3
    0
        Visit 14
    1
    0
        Missing
    104
    55
    No statistical analyses for this end point

    Secondary: Seroconversion at end of follow-up

    Close Top of page
    End point title
    Seroconversion at end of follow-up
    End point description
    End point type
    Secondary
    End point timeframe
    Week 48-72.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: Subjects
        Yes
    2
    0
        No
    4
    0
        Missing
    104
    55
    No statistical analyses for this end point

    Secondary: HBsAg levels at all measurement times

    Close Top of page
    End point title
    HBsAg levels at all measurement times
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: IU/ml
        arithmetic mean (standard deviation)
    7001.3 ( 13903.8 )
    9277.5 ( 17574.4 )
    No statistical analyses for this end point

    Secondary: Decline of HBs antigen at week 36 (mITT)

    Close Top of page
    End point title
    Decline of HBs antigen at week 36 (mITT)
    End point description
    36 Weeks.
    End point type
    Secondary
    End point timeframe
    Differences between screening after 36 weeks compared to baseline. Modified Intention-to-treat (mITT) population was investigated.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: IU/ml
        geometric mean (confidence interval 95%)
    0.1931 (0.1304 to 0.2858)
    0.7937 (0.4749 to 1.3266)
    No statistical analyses for this end point

    Secondary: Decline of HBs antigen at week 48 (mITT)

    Close Top of page
    End point title
    Decline of HBs antigen at week 48 (mITT)
    End point description
    Differences between screening after 48 weeks compared to baseline. Modified Intention-to-treat (mITT) population was investigated.
    End point type
    Secondary
    End point timeframe
    48 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: IU/ml
        geometric mean (confidence interval 95%)
    0.1859 (0.1279 to 0.2701)
    0.7372 (0.4350 to 1.2494)
    No statistical analyses for this end point

    Secondary: Decline of HBs antigen at week 72 (mITT)

    Close Top of page
    End point title
    Decline of HBs antigen at week 72 (mITT)
    End point description
    Differences between screening after 72 weeks compared to baseline. Modified Intention-to-treat (mITT) population was investigated.
    End point type
    Secondary
    End point timeframe
    72 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: IU/ml
        geometric mean (confidence interval 95%)
    0.2535 (0.1849 to 0.3476)
    0.6581 (0.4225 to 1.0250)
    No statistical analyses for this end point

    Secondary: Systolic Blood pressure week 24

    Close Top of page
    End point title
    Systolic Blood pressure week 24
    End point description
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: mmHg
        arithmetic mean (standard deviation)
    127.34 ( 14.29 )
    129.85 ( 16.92 )
    No statistical analyses for this end point

    Secondary: Systolic Blood pressure week 36

    Close Top of page
    End point title
    Systolic Blood pressure week 36
    End point description
    End point type
    Secondary
    End point timeframe
    36 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: mmHg
        arithmetic mean (standard deviation)
    126.36 ( 14.43 )
    131.00 ( 16.86 )
    No statistical analyses for this end point

    Secondary: Systolic Blood Pressure (EoT)

    Close Top of page
    End point title
    Systolic Blood Pressure (EoT)
    End point description
    End point type
    Secondary
    End point timeframe
    48 weeks/ end of study.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: mmHg
        arithmetic mean (standard deviation)
    124.75 ( 14.16 )
    130.13 ( 15.67 )
    No statistical analyses for this end point

    Secondary: Pulse (EoT)

    Close Top of page
    End point title
    Pulse (EoT)
    End point description
    End point type
    Secondary
    End point timeframe
    End of trial. 48 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: bpm
        arithmetic mean (standard deviation)
    73.86 ( 9.48 )
    72.30 ( 7.63 )
    No statistical analyses for this end point

    Secondary: body weight week 12

    Close Top of page
    End point title
    body weight week 12
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg
        arithmetic mean (standard deviation)
    79.64 ( 12.93 )
    79.35 ( 15.49 )
    No statistical analyses for this end point

    Secondary: body weight week 24

    Close Top of page
    End point title
    body weight week 24
    End point description
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg
        arithmetic mean (standard deviation)
    78.77 ( 12.40 )
    79.64 ( 15.61 )
    No statistical analyses for this end point

    Secondary: body weight week 36

    Close Top of page
    End point title
    body weight week 36
    End point description
    End point type
    Secondary
    End point timeframe
    36 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg
        arithmetic mean (standard deviation)
    79.02 ( 11.63 )
    79.13 ( 15.44 )
    No statistical analyses for this end point

    Secondary: body weight (EoT)

    Close Top of page
    End point title
    body weight (EoT)
    End point description
    End point type
    Secondary
    End point timeframe
    End of Trial. 48 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg
        arithmetic mean (standard deviation)
    77.72 ( 12.33 )
    79.79 ( 15.12 )
    No statistical analyses for this end point

    Secondary: BMI week 12

    Close Top of page
    End point title
    BMI week 12
    End point description
    End point type
    Secondary
    End point timeframe
    12 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg/m²
        arithmetic mean (standard deviation)
    26.19 ( 3.86 )
    26.76 ( 4.31 )
    No statistical analyses for this end point

    Secondary: BMI week 24

    Close Top of page
    End point title
    BMI week 24
    End point description
    End point type
    Secondary
    End point timeframe
    24 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg/m²
        arithmetic mean (standard deviation)
    25.91 ( 3.61 )
    26.85 ( 4.38 )
    No statistical analyses for this end point

    Secondary: BMI week 36

    Close Top of page
    End point title
    BMI week 36
    End point description
    End point type
    Secondary
    End point timeframe
    Week 36.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg/m²
        arithmetic mean (standard deviation)
    25.88 ( 3.56 )
    26.75 ( 4.37 )
    No statistical analyses for this end point

    Secondary: BMI (EoT)

    Close Top of page
    End point title
    BMI (EoT)
    End point description
    End point type
    Secondary
    End point timeframe
    End of Trial. 48 weeks.
    End point values
    Intervention Group (Pegasys®) Control Group
    Number of subjects analysed
    110
    55
    Units: kg/m²
        arithmetic mean (standard deviation)
    25.56 ( 3.60 )
    26.88 ( 4.28 )
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    In this trial, the period of observation for adverse events extended from the time the subject had signed the informed consent document up to the end of follow up at week 72 (visit 15 of the treatment group or visit 7 of the control group).
    Adverse event reporting additional description
    If the investigator detected a serious adverse event after the period of observation, considering the event possibly related to this trial, he should contact the sponsor to determine how the adverse event should be documented & reported. Serious adverse events had to be immediately (within 24h of the investigator’s awareness) reported to IZKS Mainz
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Intervention Group (Pegasys®)
    Reporting group description
    The group received addiotional treatment with Pegasys in the following treatment period. After the treatment period, both groups were treated with the standard therapeutic use of Nucleos(t)ides.

    Reporting group title
    Control Group
    Reporting group description
    Group receiving the standard nucleos(t)ide treatment without the add-on drug [pegylated Interferon alfa-2a (Pegasys®)].

    Serious adverse events
    Intervention Group (Pegasys®) Control Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 112 (11.61%)
    4 / 58 (6.90%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Aortic valve replacement
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Internal fixation of fracture
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pain
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyarthritis
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Postmenopausal haemorrhage
    Additional description: recovering/resolving
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Nasal turbinate hypertrophy
    Additional description: hypertrophy recovering/resolving
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Facial bones fracture
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
    Additional description: recovering/resolving
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal haemorrhage
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin hyperpigmentation
    Additional description: recovered/resolved
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
    Additional description: recovered/resolved
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
    Additional description: recovered/resolved with sequel
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
    Additional description: recovered/resolved
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pyelonephritis
    Additional description: recovered/resolved
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
    Additional description: recovered/resolved
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chlamydial infection
    Additional description: recovering/resolving
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Intervention Group (Pegasys®) Control Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    106 / 112 (94.64%)
    20 / 58 (34.48%)
    Investigations
    Transaminases increased
         subjects affected / exposed
    6 / 112 (5.36%)
    0 / 58 (0.00%)
         occurrences all number
    9
    0
    Weight decreased
         subjects affected / exposed
    8 / 112 (7.14%)
    1 / 58 (1.72%)
         occurrences all number
    8
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    11 / 112 (9.82%)
    0 / 58 (0.00%)
         occurrences all number
    18
    0
    Headache
         subjects affected / exposed
    40 / 112 (35.71%)
    0 / 58 (0.00%)
         occurrences all number
    48
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    11 / 112 (9.82%)
    0 / 58 (0.00%)
         occurrences all number
    19
    0
    Fatigue
         subjects affected / exposed
    48 / 112 (42.86%)
    2 / 58 (3.45%)
         occurrences all number
    52
    2
    Influenza like illness
         subjects affected / exposed
    13 / 112 (11.61%)
    2 / 58 (3.45%)
         occurrences all number
    21
    2
    Injection site erythema
         subjects affected / exposed
    11 / 112 (9.82%)
    0 / 58 (0.00%)
         occurrences all number
    12
    0
    Pyrexia
         subjects affected / exposed
    25 / 112 (22.32%)
    0 / 58 (0.00%)
         occurrences all number
    28
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    8 / 112 (7.14%)
    0 / 58 (0.00%)
         occurrences all number
    11
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    11 / 112 (9.82%)
    6 / 58 (10.34%)
         occurrences all number
    11
    10
    Diarrhoea
         subjects affected / exposed
    9 / 112 (8.04%)
    1 / 58 (1.72%)
         occurrences all number
    12
    1
    Nausea
         subjects affected / exposed
    12 / 112 (10.71%)
    1 / 58 (1.72%)
         occurrences all number
    13
    1
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    6 / 112 (5.36%)
    0 / 58 (0.00%)
         occurrences all number
    6
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 112 (8.04%)
    2 / 58 (3.45%)
         occurrences all number
    10
    2
    Oropharyngeal pain
         subjects affected / exposed
    7 / 112 (6.25%)
    0 / 58 (0.00%)
         occurrences all number
    8
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    17 / 112 (15.18%)
    0 / 58 (0.00%)
         occurrences all number
    17
    0
    Dry skin
         subjects affected / exposed
    7 / 112 (6.25%)
    0 / 58 (0.00%)
         occurrences all number
    7
    0
    Pruritus
         subjects affected / exposed
    15 / 112 (13.39%)
    0 / 58 (0.00%)
         occurrences all number
    17
    0
    Rash
         subjects affected / exposed
    8 / 112 (7.14%)
    0 / 58 (0.00%)
         occurrences all number
    10
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    9 / 112 (8.04%)
    0 / 58 (0.00%)
         occurrences all number
    10
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    31 / 112 (27.68%)
    0 / 58 (0.00%)
         occurrences all number
    45
    0
    Back pain
         subjects affected / exposed
    15 / 112 (13.39%)
    2 / 58 (3.45%)
         occurrences all number
    17
    3
    Myalgia
         subjects affected / exposed
    19 / 112 (16.96%)
    0 / 58 (0.00%)
         occurrences all number
    21
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    28 / 112 (25.00%)
    3 / 58 (5.17%)
         occurrences all number
    31
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 112 (5.36%)
    0 / 58 (0.00%)
         occurrences all number
    9
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Dec 2011
    Added following inclusion criteria: -Treatment with a nucleos(t)ide regimen (lamivudine, adefovir, entecavir, tenofovir or one of the following combinations: lamivudine/adefovir, lamivudine/tenofovir, entecavir/adefovir or entecavir/tenofovir) and a fully suppressed viral load for at least 12 months (below limit of detection in conventional HBV-PCR assays, i.e. <116 copies/ml). Added following exclusion criteria: -Preexisting polyneuropathy -If polyneuropathy develops and is confirmed by a neurologist, withdrawal will be discussed according to severity of the symptoms Declared the following as secondary objectives: -To evaluate safety and tolerability of pegylated interferon alfa-2a when combined with tenofovir, entecavir, lamivudine, adefovir, or a combination of lamivudine or entecavir with adefovir or tenofovir. Added the following information to the basic treatment section: The known dosing instructions, contraindications, side effects and risks for each drug must be taken into account accoring to the maufacturers’ recommendations. Regular laboratory and clinical assessments throughout the course of this study are to provide adequate monitoring of potential toxicities. Added the following info on physical examination: As an increased incidence of polyneuropathy was observed during combination therapy with pegylated interferon alfa-2a and telbivudine, special attention should be paid to the development of polyneuropathy or other neurological symptoms in subjects on combination therapy. Investigators need to question patients about development of hyp- or dysesthesia, muscle weakness or any other neurological symptoms. If neurological symptoms occur, they need to be documented as adverse events, and the patients will then be referred to a neurologist for further examination.
    19 Apr 2013
    The amendment contains the change of: - the coordinating investigator - the inclusion criterion “HBsAg ≥1000 IU/ml” to “HBsAg ≥100 IU/ml” - the following exclusion criteria: - Decompensated liver disease, or history of decompensated liver disease, as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy, coagulopathy, varices, history of varicose bleeding, or any othe clinical evidence of decompensation. (Patients with stable liver cirrhosis are eligible for this study, if a history of decompensated liver disease as outlined above has been excluded.) -Usage of any investigational drugs within 3 months before enrolment removed: Histologically proven liver cirrhosis (exclusion criteria). Earlier: Usage of any investigational drugs within 12 months before enrolment.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA