Study to Evaluate the 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). - Full Text View

Purpose

The purpose of this study is to 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 CHB subjects as determined by loss of HBsAg.

Condition	Intervention	Phase
Chronic Hepatitis B	Drug: Tenofovir disoproxil fumarate 300 mg(TDF) and Peginterferon α-2a 180 µg(PEG) Drug: Tenofovir Disoproxil Fumarate, Peginterferon α-2a Drug: Tenofovir Disoproxil Fumarate Drug: Peginterferon α-2a	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:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Formic acid Tenofovir Tenofovir Disoproxil Fumarate Recombinant Hepatitis B vaccine Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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
Virological response [ Time Frame: Baseline through Week 120 ] [ Designated as safety issue: No ]
Evaluate virological response (HBV DNA < 400copies/mL)

Estimated Enrollment:	720
Study Start Date:	March 2011
Estimated Study Completion Date:	September 2015
Estimated Primary Completion Date:	September 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm A-Treatment Arm 1 Subjects will be treated with Tenofovir disoproxil fumarate 300 mg(TDF) and Peginterferon α-2a 180 µg(PEG) concomitantly for 48 weeks.	Drug: Tenofovir disoproxil fumarate 300 mg(TDF) and Peginterferon α-2a 180 µg(PEG) Tenofovir disoproxil fumarate 300 mg(TDF)PO once daily in combination with Peginterferon α-2a 180 µg(PEG) subcutaneous injection once weekly for 48 weeks. Drug: Tenofovir Disoproxil Fumarate, Peginterferon α-2a Tenofovir disoproxil fumarate 300 mg PO once daily in combination with Peginterferon α-2a 180 µg subcutaneous injection once weekly for 16 weeks and Tenofovir disoproxil fumarate 300 mg PO once daily for additional 32 weeks.
Experimental: Arm B- Treatment arm 2 Subjects will be treated with Tenofovir disoproxil fumarate 300 mg(TDF) and Peginterferon α-2a 180 µg(PEG) concomitantly for 16 weeks followed by Tenofovir disoproxil fumarate 300 mg(TDF)alone for another 32 weeks (total 48 weeks).	Drug: Tenofovir Disoproxil Fumarate, Peginterferon α-2a Tenofovir disoproxil fumarate 300 mg PO once daily in combination with Peginterferon α-2a 180 µg subcutaneous injection once weekly for 16 weeks and Tenofovir disoproxil fumarate 300 mg PO once daily for additional 32 weeks. Drug: Tenofovir Disoproxil Fumarate Tenofovir disoproxil fumarate 300 mg PO once daily for 120 weeks. Drug: Peginterferon α-2a Peginterferon α-2a 180 µg subcutaneous injection once weekly for 48 weeks.
Active Comparator: Arm C- Active control Arm 1 Subjects will be treated with Tenofovir disoproxil fumarate 300 mg(TDF) continuously through 120 weeks.	Drug: Tenofovir Disoproxil Fumarate Tenofovir disoproxil fumarate 300 mg PO once daily for 120 weeks.
Active Comparator: Arm D- Active control Arm 2 Subjects will be treated with Peginterferon α-2a 180 µg(PEG) for 48 weeks.	Drug: Peginterferon α-2a Peginterferon α-2a 180 µg subcutaneous injection once weekly for 48 weeks.

Eligibility

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

Criteria

Inclusion Criteria:

Adult subjects (aged 18-75) with CHB (positive for serum HBsAg or HaBV DNA for at least 6 months)prior to baseline.
Anti-HBV treatment naïve subjects and subjects 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 HBeAg+ subjects and HBV DNA ≥ 2,000 IU/ml for HBeAg- subjects
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 female subjects of childbearing potential
All sexually active female subjects 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 female subjects 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/mm3, platelet < 100,000/mm3, hemoglobin < 10 g/dL (female) or < 11 g/dL (male)
History of severe depression or severe psychiatric disease
Thyroid dysfunction
Co-infection with HIV, HCV or HDV
Pregnant

Contacts and Locations

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

Show 166 Study Locations

Sponsors and Collaborators

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:	February 25, 2013
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, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections

DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on June 13, 2013

Study to Evaluate the 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)