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

Gilead Sciences

Status and phase: Completed; Phase 4

Conditions: Chronic Hepatitis B

Treatments: Drug: Peg-IFN; Drug: TDF

Study type: Interventional

Funder types: Industry

Identifiers

NCT01277601

2010-024586-45 (EudraCT Number)

GS-US-174-0149

Details and patient eligibility

About

The primary objective of this study is to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (Peg-IFN) combination therapy for 48 weeks versus standard of care TDF monotherapy or Peg-IFN monotherapy for 48 weeks in non-cirrhotic adults with chronic hepatitis B virus (HBV) as determined by loss of hepatitis B surface antigen (HBsAg).

The study will consist of 2 phases for participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks 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 meeting TDF retreatment and flare management criteria will be eligible to receive TDF monotherapy during a retreatment phase, up to Week 120.

Enrollment: 751 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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751 participants in 4 patient groups

TDF+Peg-IFN 48 Weeks

Experimental group

Description:

TDF plus Peg-IFN for 48 weeks

Treatment:

Drug: TDF

Drug: Peg-IFN

TDF 48 Weeks + Peg-IFN 16 Weeks

Experimental group

Description:

TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks

Treatment:

Drug: TDF

Drug: Peg-IFN

TDF 120 Weeks

Active Comparator group

Description:

TDF monotherapy for 120 weeks

Treatment:

Drug: TDF

Peg-IFN 48 Weeks

Active Comparator group

Description:

Peg-IFN monotherapy for 48 weeks

Treatment:

Drug: Peg-IFN