Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon α-2a vs Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon α-2a Monotherapy for 48 Weeks in Chronic Hepatitis B(CHB). (TDF PEG CHB)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01277601
First received: January 13, 2011
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B
Drug: TDF
Drug: PEG
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion 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: Week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion 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: Week 72 ] [ Designated as safety issue: No ]
  • Proportion of participants who experience HBsAg loss at Week 96 and Week 120 [ Time Frame: Weeks 96 and 120 ] [ Designated as safety issue: No ]
  • Proportion of participants with virological response (hepatitis B virus [HBV] DNA level < 117 IU/mL) at Weeks 72, 96, and 120 [ Time Frame: Weeks 72, 96, and 120 ] [ Designated as safety issue: No ]
  • Proportion of participants with serological response (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 ]
  • Proportion of participants who experience biochemical response at Weeks 72, 96, and 120 [ Time Frame: Weeks 72, 96, and 120 ] [ Designated as safety issue: No ]
    Biochemical response is defined as having alanine aminotransferase (ALT) < 30 for males and < 19 for females (based on the American Association for the Study of Liver Diseases [AASLD] 2008 guidelines); ALT < 42 for males and < 32 for females (based on central lab upper limit of the normal range [ULN] for ALT).

  • Proportion of participants who require reinitiation or change of anti-HBV therapy while on therapy or posttreatment [ Time Frame: Up to 120 weeks ] [ Designated as safety issue: No ]

Enrollment: 751
Study Start Date: April 2011
Estimated Study Completion Date: July 2015
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDF+PEG 48 wk
Participants will receive TDF plus PEG concomitantly for 48 weeks.
Drug: TDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily
Other Name: Viread®
Drug: PEG
Peginterferon α-2a (PEG) 180 µg administered via subcutaneous injection once weekly
Other Name: Pegasys®
Experimental: TDF+PEG 16 wk, TDF 32 wk
Participants will receive TDF plus PEG concomitantly for 16 weeks, followed by TDF alone for 32 weeks (total 48 weeks).
Drug: TDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily
Other Name: Viread®
Drug: PEG
Peginterferon α-2a (PEG) 180 µg administered via subcutaneous injection once weekly
Other Name: Pegasys®
Active Comparator: TDF 120 wk
Participants will receive TDF continuously through 120 weeks.
Drug: TDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily
Other Name: Viread®
Active Comparator: PEG 48 wk
Participants will receive PEG for 48 weeks.
Drug: PEG
Peginterferon α-2a (PEG) 180 µg administered via subcutaneous injection once weekly
Other Name: Pegasys®

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (aged 18-75) with CHB (positive for serum HBsAg or HBV DNA for at least 6 months) prior to baseline.
  • Anti-HBV treatment naive adults and 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 HBeAg -HBV DNA ≥ 20,000 IU/ml for individuals with HBeAg+ and HBV DNA ≥ 2,000 IU/ml for individuals with HBeAg-
  • 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
  • A negative serum pregnancy test is required for females of childbearing potential
  • All sexually active females of childbearing potential must agree to use a protocol recommended method of contraception during heterosexual intercourse 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 renal, cardiovascular, pulmonary, neurological, autoimmune disease or bone disease (e.g., 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
  • Co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
  • Pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01277601

  Show 166 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Eduardo B Martins, MD, DP Gilead Sciences
  More Information

No publications provided

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
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Chronic Hepatitis B
Hep B
Non cirrhotic
Treatment naive
Tenofovir disoproxil fumarate (TDF)
Peginterferon α-2a (PEG)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014