Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN 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: July 15, 2016
Last verified: July 2016
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-IFN

  Participant Flow
  Hide Participant Flow

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 at study sites in North America, Europe, Asia, and Australia. The first participant was screened on 12 April 2011. The last study visit occurred on 17 July 2015.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1597 participants were screened.

Reporting Groups
  Description
TDF+Peg-IFN 48 Weeks Tenofovir disoproxil fumarate (TDF) 300 mg tablet once daily plus peginterferon α-2a (Peg-IFN) 180 µg subcutaneous (s.c.) injection once weekly for 48 weeks
TDF 48 Weeks + Peg-IFN 16 Weeks TDF 300 mg tablet once daily plus Peg-IFN 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 Weeks TDF 300 mg tablet once daily for 120 weeks
Peg-IFN 48 Weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks

Participant Flow:   Overall Study
    TDF+Peg-IFN 48 Weeks   TDF 48 Weeks + Peg-IFN 16 Weeks   TDF 120 Weeks   Peg-IFN 48 Weeks
STARTED   188   187   190   186 
COMPLETED   151   139   163   150 
NOT COMPLETED   37   48   27   36 
Adverse Event                5                3                0                7 
Withdrawal by Subject                18                21                8                17 
Lost to Follow-up                7                9                4                2 
Physician Decision                3                5                1                6 
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                2                5                0 
Subject Terminated from Study by Sponsor                0                1                0                2 



  Baseline Characteristics
  Hide Baseline Characteristics

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 drug. Participants were analyzed by actual treatment received.

11 participants were never dosed are not included in the Safety Analysis Set due to the following reasons for discontinuation: 7 = Subject Never Dosed with Study Drug; 4 = Withdrawal by Subject.


Reporting Groups
  Description
TDF+Peg-IFN 48 Weeks TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
TDF 48 Weeks + Peg-IFN 16 Week TDF 300 mg tablet once daily plus Peg-IFN 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 Weeks TDF 300 mg tablet once daily for 120 weeks
Peg-IFN 48 Weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
Total Total of all reporting groups

Baseline Measures
   TDF+Peg-IFN 48 Weeks   TDF 48 Weeks + Peg-IFN 16 Week   TDF 120 Weeks   Peg-IFN 48 Weeks   Total 
Overall Participants Analyzed 
[Units: Participants]
 186   184   185   185   740 
Age 
[Units: Years]
Mean (Standard Deviation)
 38  (10.7)   37  (9.9)   36  (10.8)   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)   7.02  (1.550)   6.94  (1.619)   7.04  (1.553) 
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
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN 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-IFN (16 Weeks) Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone   [ Time Frame: Baseline; Week 72 ]

3.  Secondary:   Percentage of Participants With HBsAg Loss at Weeks 96 and 120   [ Time Frame: Baseline; Weeks 96 and 120 ]

4.  Secondary:   Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120   [ Time Frame: Baseline; Weeks 72, 96, and 120 ]

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

6.  Secondary:   Percentage of Participants With HBeAg Loss and Seroconversion at Week 96   [ Time Frame: Baseline; Week 96 ]

7.  Secondary:   Percentage of Participants With HBeAg Loss and Seroconversion at Week 120   [ Time Frame: Baseline; Week 120 ]

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

9.  Secondary:   Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 96   [ Time Frame: Week 96 ]

10.  Secondary:   Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 120   [ Time Frame: Week 120 ]

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

12.  Secondary:   Percentage of Participants With Normal ALT at Week 96   [ Time Frame: Week 96 ]

13.  Secondary:   Percentage of Participants With Normal ALT at Week 120   [ Time Frame: Week 120 ]

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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


Publications of Results:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01277601     History of Changes
Other Study ID Numbers: GS-US-174-0149
2010-024586-45 ( EudraCT Number )
Study First Received: January 13, 2011
Results First Received: August 10, 2015
Last Updated: July 15, 2016
Health Authority: United States: Food and Drug Administration