Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Positive for Hepatitis B e Antigen

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HBeAg-positive Chronic Hepatitis B

Treatments: Drug: TDF Placebo; Drug: TAF Placebo; Drug: TAF; Drug: TDF

Study type: Interventional

Funder types: Industry

Identifiers

NCT01940471

2013-000636-10 (EudraCT Number)

GS-US-320-0110

Details and patient eligibility

About

The primary objective of this study is to compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection.

Full description

This study GS-US-320-0110 is a multi-center clinical trial planned to enroll participants in multiple countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study before China was able to participate. Therefore, details for the China cohort are registered separately (NCT02836249) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

Enrollment: 875 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.

• Adult males and non-pregnant, non-lactating females.

• Documented evidence of chronic HBV infection.

• HBeAg-positive, chronic hepatitis B with all of the following:

  • HBeAg-positive at screening.
  • Screening HBV DNA ≥ 2 x 10^4 IU/mL
  • Screening serum alanine aminotransferase (ALT) level > 60 U/L (males) or > 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN).

• Treatment-naive participants (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue) OR treatment-experienced participants (defined as participants meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue).

• Previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit.

• Adequate renal function.

• Normal electrocardiogram (ECG).

Key Exclusion Criteria:

• Females who are breastfeeding.
• Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
• Co-infection with hepatitis C virus, human immunodeficiency virus (HIV), or hepatitis D virus.
• Evidence of hepatocellular carcinoma .
• Any history of, or current evidence of, clinical hepatic decompensation.
• Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) > 10 x ULN.
• Received solid organ or bone marrow transplant.
• History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; individuals under evaluation for possible malignancy are not eligible.
• Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
• Individuals receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients.
• Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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875 participants in 3 patient groups

TAF 25 mg

Experimental group

Description:

TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).

Treatment:

Drug: TDF Placebo

Drug: TAF

TDF 300 mg

Active Comparator group

Description:

TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).

Treatment:

Drug: TDF

Drug: TAF Placebo

Open-label TAF

Experimental group

Description:

All participants who complete the double-blind period (96 weeks or 144 weeks) will be eligible to receive open-label TAF until Week 384 of the study. After the end of study treatment, participants can either switch to commercially available anti-HBV treatments in their country or will be followed every 4 weeks, for up to 24 weeks off treatment (treatment-free follow-up (TFFU)) for safety assessment.

Treatment:

Drug: TAF