Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (PEG) Versus TDF or PEG Monotherapy in Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01277601
First received: January 13, 2011
Last updated: September 9, 2015
Last verified: September 2015
Results First Received: August 10, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Chronic Hepatitis B
Interventions: Drug: TDF
Drug: PEG

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled in sites in North America, Europe, Asia, and Australia.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1597 participants were screened. Data submitted are partial results based on the analysis performed on data collected by the Primary Completion Date (August 2014). Complete data will be submitted in July 2016.

Reporting Groups
  Description
TDF+PEG 48 Week Tenofovir disoproxil fumarate (TDF) 300 mg tablet once daily plus peginterferon α-2a (PEG) 180 µg subcutaneous (s.c.) injection once weekly for 48 weeks
TDF 48 Week+PEG 16 Week TDF 300 mg tablet once daily plus PEG 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks
TDF 120 Week TDF 300 mg tablet once daily for 120 weeks
PEG 48 Week PEG 180 µg s.c. injection once weekly for 48 weeks

Participant Flow:   Overall Study
    TDF+PEG 48 Week     TDF 48 Week+PEG 16 Week     TDF 120 Week     PEG 48 Week  
STARTED     188     187     190     186  
COMPLETED     43     37     34     38  
NOT COMPLETED     145     150     156     148  
Randomized but Not Treated                 2                 3                 5                 1  
Adverse Event                 5                 4                 0                 6  
Withdrawal by Subject                 15                 17                 8                 16  
Lost to Follow-up                 7                 2                 3                 1  
Physician Decision                 3                 5                 1                 5  
Pregnancy                 2                 2                 4                 1  
Noncompliance with Study Drug                 1                 3                 2                 0  
Subject Never Dosed with Study Drug                 1                 2                 3                 1  
Protocol Violation                 0                 1                 5                 0  
Subject Terminated from Study by Sponsor                 0                 1                 0                 2  
Subject Still on Study                 109                 110                 125                 115  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: participants who were randomized and received at least 1 dose of study medication

Reporting Groups
  Description
TDF+PEG 48 Week TDF 300 mg tablet once daily plus PEG 180 µg s.c. injection once weekly for 48 weeks
TDF 48 Weeks+PEG 16 Week TDF 300 mg tablet once daily plus PEG 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks
TDF 120 Week TDF 300 mg tablet once daily for 120 weeks
PEG 48 Week PEG 180 µg s.c. injection once weekly for 48 weeks
Total Total of all reporting groups

Baseline Measures
    TDF+PEG 48 Week     TDF 48 Weeks+PEG 16 Week     TDF 120 Week     PEG 48 Week     Total  
Number of Participants  
[units: participants]
  186     184     185     185     740  
Age  
[units: years]
Mean (Standard Deviation)
  38  (10.7)     37  (9.9)     36  (10.9)     38  (10.5)     37  (10.5)  
Gender  
[units: participants]
         
Female     59     65     64     66     254  
Male     127     119     121     119     486  
Ethnicity (NIH/OMB)  
[units: participants]
         
Hispanic or Latino     4     4     3     7     18  
Not Hispanic or Latino     182     179     181     177     719  
Unknown or Not Reported     0     1     1     1     3  
Race/Ethnicity, Customized  
[units: participants]
         
Asian     142     134     141     137     554  
Black or African American     5     3     4     6     18  
Native Hawaiian or Other Pacific Islander     2     0     0     1     3  
White     36     45     39     41     161  
Other     1     2     1     0     4  
Region of Enrollment  
[units: participants]
         
Romania     12     15     13     9     49  
Singapore     7     5     7     8     27  
Hong Kong     25     24     27     21     97  
United States     19     17     23     26     85  
United Kingdom     2     3     1     4     10  
Portugal     0     3     0     0     3  
India     10     5     9     6     30  
Spain     3     3     3     5     14  
Greece     0     3     2     4     9  
Canada     19     14     14     11     58  
Netherlands     2     1     0     1     4  
Turkey     5     6     6     7     24  
Taiwan     20     15     12     19     66  
Korea, Republic of     34     38     38     35     145  
Poland     4     7     6     5     22  
Italy     2     1     4     4     11  
Australia     10     14     15     14     53  
France     6     3     1     3     13  
Germany     6     7     4     3     20  
Hepatitis B Surface Antigen (HBsAg)  
[units: log 10 (IU/mL)]
Mean (Standard Deviation)
  3.88  (0.840)     3.84  (0.849)     3.89  (0.812)     3.76  (0.844)     3.84  (0.836)  
Hepatitis B e Antigen (HBeAg) Status  
[units: participants]
         
Reactive     108     105     109     106     428  
Nonreactive     78     79     76     79     312  
Hepatitis B Virus (HBV) DNA  
[units: log 10 (IU/mL)]
Mean (Standard Deviation)
  7.06  (1.542)     7.13  (1.505)     7.03  (1.539)     6.94  (1.619)     7.04  (1.550)  
HBV Genotype  
[units: participants]
         
Genotype A     17     16     14     14     61  
Genotype B     50     51     49     53     203  
Genotype C     78     79     78     79     314  
Genotype D     39     36     41     38     154  
Genotype E-H     2     2     3     1     8  
Alanine Aminotransferase (ALT)  
[units: U/L]
Mean (Standard Deviation)
  121.2  (180.82)     112.2  (94.44)     100.9  (67.65)     106.6  (91.51)     110.3  (116.94)  



  Outcome Measures
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1.  Primary:   Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus PEG Combination Versus PEG Alone for 48 Weeks or TDF Alone   [ Time Frame: Baseline; Week 72 ]

2.  Secondary:   Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With TDF (48 Weeks) Plus PEG (16 Weeks) Combination Versus PEG Alone for 48 Weeks or TDF Alone   [ Time Frame: Baseline; Week 72 ]

3.  Secondary:   Percentage of Participants With HBsAg Seroconversion at Week 72   [ Time Frame: Baseline; Week 72 ]

4.  Secondary:   Percentage of Participants With HBeAg Loss and Seroconversion at Week 72   [ Time Frame: Baseline; Week 72 ]

5.  Secondary:   Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72   [ Time Frame: Week 72 ]

6.  Secondary:   Percentage of Participants With Normal ALT at Week 72   [ Time Frame: Week 72 ]

7.  Secondary:   Percentage of Participants Who Required Retreatment   [ Time Frame: Up to 120 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
There were no limitations affecting the analysis or results.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
e-mail: ClinicalTrialDisclosures@gilead.com


No publications provided by Gilead Sciences

Publications automatically indexed to this study:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01277601     History of Changes
Other Study ID Numbers: GS-US-174-0149
Study First Received: January 13, 2011
Results First Received: August 10, 2015
Last Updated: September 9, 2015
Health Authority: United States: Food and Drug Administration