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

January 13, 2011
September 9, 2015
April 2011
August 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]

Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. Proportions are based on a Kaplan-Meier estimate.

The analysis visit window for Week 72 comprised study Days 491 (Week 70) through 546 (Week 78), so results up to Week 78 are included in this analysis.

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: 72 Weeks ] [ Designated as safety issue: No ]
The proportion of subjects 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.
Complete list of historical versions of study NCT01277601 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]

    Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. Proportions are based on a Kaplan-Meier estimate.

    The analysis visit window for Week 72 comprised study Days 491 (Week 70) through 546 (Week 78), so results up to Week 78 are included in this analysis.

  • Percentage of Participants With HBsAg Seroconversion at Week 72 [ Time Frame: Baseline; Week 72 ] [ Designated as safety issue: No ]

    HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. Proportions are based on a Kaplan-Meier estimate.

    The analysis visit window for Week 72 comprised study Days 491 (Week 70) through 546 (Week 78), so results up to Week 78 are included in this analysis.

  • Percentage of Participants With HBeAg Loss and Seroconversion at Week 72 [ Time Frame: Baseline; Week 72 ] [ Designated as safety issue: No ]

    Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit.

    For the TDF+PEG 48 week, TDF 48 week+PEG 16 week, and PEG 48 week groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.

  • Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    For the TDF+PEG 48 week, TDF 48 week+PEG 16 week, and PEG 48 week groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.
  • Percentage of Participants With Normal ALT at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]

    Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT).

    For the TDF+PEG 48 week, TDF 48 week+PEG 16 week, and PEG 48 week groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.

  • Percentage of Participants Who Required Retreatment [ Time Frame: Up to 120 weeks ] [ Designated as safety issue: No ]
    Participants in the TDF 120 week group were not eligible to enter the retreatment phase and are not presented.
  • 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: 72 Weeks ] [ Designated as safety issue: No ]
    The proportion of subjects 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.
  • HBsAg loss at Week 96 and Week 120 [ Time Frame: Week 96 and Week 120 ] [ Designated as safety issue: No ]
    The proportion of subjects who experience HBsAg loss at Week 96 and Week 120
  • Rate of quantitative HBsAg decline during the study [ Time Frame: Baseline through Week 120 ] [ Designated as safety issue: No ]
    The rate of quantitative HBsAg decline during the study
  • HBV DNA level < 400 copies/mL at Weeks 72, 96 and 120 [ Time Frame: Weeks 72, 96 and 120 ] [ Designated as safety issue: No ]
    The proportion of subjects with virological response (HBV DNA level < 400 copies/mL) at Weeks 72, 96 and 120
  • HBeAg loss and seroconversion, and HBsAg seroconversion at Weeks 72, 96 and 120 [ Time Frame: Weeks 72, 96 and 120 ] [ Designated as safety issue: No ]
    The proportion of subjects with serological response (HBeAg loss and seroconversion, and HBsAg seroconversion) at Weeks 72, 96 and 120
  • ALT<ULN at Weeks 72, 96 and 120 [ Time Frame: Weeks 72, 96 and 120 ] [ Designated as safety issue: No ]
    The proportion of subjects who experience biochemical response (ALT<ULN) at Weeks 72, 96 and 120
  • Requiring re-initiation or change of therapy while on therapy or post-treatment [ Time Frame: Baseline through Week 120 ] [ Designated as safety issue: Yes ]
    The proportion of subjects who require re-initiation or change of therapy while on therapy or post-treatment
Not Provided
Not Provided
 
Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (PEG) Versus TDF or PEG Monotherapy in Chronic Hepatitis B
A Phase 4, Randomized, Open-label, Active-Controlled, Superiority Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon α-2a (Pegasys) Versus Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon α-2a Monotherapy for 48 Weeks in Non-Cirrhotic Subjects With HBeAg-Positive or HBeAg-Negative Chronic Hepatitis B (CHB)

This study will evaluate the safety and efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (PEG) combination therapy versus standard of care TDF monotherapy or PEG monotherapy in non-cirrhotic adults with chronic hepatitis B virus (HBV).

The study will consist of 2 phases for participants in the TDF+PEG 48 week, TDF 48 week+PEG 16 week, and PEG 48 week groups. Following an initial 48 weeks of treatment, participants in these groups will be monitored for 24 weeks for signs of worsening HBV, and those with new signs and/or symptoms will be eligible to receive TDF monotherapy during a retreatment phase, up to Week 120.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis B
  • Drug: TDF
    TDF 300 mg tablets administered orally once daily
    Other Name: Viread®
  • Drug: PEG
    PEG 180 µg administered via subcutaneous injection once weekly
    Other Name: Pegasys®
  • Experimental: TDF+PEG 48 week
    TDF plus PEG for 48 weeks
    Interventions:
    • Drug: TDF
    • Drug: PEG
  • Experimental: TDF 48 week+PEG 16 week
    TDF plus PEG for 16 weeks, followed by TDF alone for an additional 32 weeks
    Interventions:
    • Drug: TDF
    • Drug: PEG
  • Active Comparator: TDF 120 week
    TDF monotherapy for 120 weeks
    Intervention: Drug: TDF
  • Active Comparator: PEG 48 week
    PEG monotherapy for 48 weeks
    Intervention: Drug: PEG

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
751
July 2015
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adults (age 18-75) with chronic HBV (positive for serum hepatitis B surface antigen (HBsAg) or HBV DNA for at least 6 months) prior to baseline
  • Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside therapy with the last dose ≥ 24 weeks prior to screening are also eligible.
  • Positive or negative for hepatitis B e antigen (HBeAg)
  • HBV DNA ≥ 20,000 IU/ml (HBeAg-positive participants) and ≥ 2,000 IU/ml (HBeAg-negative participants)
  • Alanine aminotransferase (ALT) > 54 U/L and ≤ 400 U/L for men and > 36 U/L and ≤ 300 U/L for women
  • Creatinine clearance ≥ 70 mL/min
  • Negative serum pregnancy test for females of childbearing potential
  • Sexually active females of childbearing potential must agree to use a protocol-recommended method of contraception throughout the study and for 30 days following the last dose of study medication
  • Lactating females must agree to discontinue nursing before initiation of study investigational medicinal product

Exclusion Criteria:

  • Known bridging fibrosis or cirrhosis and/or decompensated liver disease
  • Evidence of hepatocellular carcinoma
  • Significant kidney, heart, lung, neurological, autoimmune disease, or bone disease (eg, osteomalacia,chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures)
  • Absolute neutrophil count < 1,500/mm^3, platelet < 100,000/mm^3, hemoglobin < 10 g/dL (female) or < 11 g/dL (male)
  • History of severe depression or severe psychiatric disease
  • Thyroid dysfunction
  • Coinfection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
  • Pregnant
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   France,   Germany,   Greece,   Hong Kong,   India,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Romania,   Singapore,   Spain,   Taiwan,   Turkey,   United Kingdom
 
NCT01277601
GS-US-174-0149
No
Not Provided
Not Provided
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Eduardo B Martins, MD Gilead Sciences
Gilead Sciences
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP