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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01940471




Registration number
NCT01940471
Ethics application status
Date submitted
20/08/2013
Date registered
12/09/2013
Date last updated
10/10/2023

Titles & IDs
Public title
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
Scientific title
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Positive, Chronic Hepatitis B
Secondary ID [1] 0 0
2013-000636-10
Secondary ID [2] 0 0
GS-US-320-0110
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HBeAg-positive Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TAF
Treatment: Drugs - TDF
Treatment: Drugs - TAF Placebo
Treatment: Drugs - TDF Placebo

Experimental: TAF 25 mg - TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3).

Active Comparator: TDF 300 mg - TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3).

Experimental: Open-label TAF - 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: Drugs: TAF
25 mg tablet administered orally once daily

Treatment: Drugs: TDF
300 mg tablet administered orally once daily

Treatment: Drugs: TAF Placebo
Tablet administered orally once daily

Treatment: Drugs: TDF Placebo
Tablet administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Timepoint [2] 0 0
Baseline, Week 48
Secondary outcome [3] 0 0
Percent Change From Baseline in Spine BMD at Week 48
Timepoint [3] 0 0
Baseline, Week 48
Secondary outcome [4] 0 0
Change From Baseline at Week 48 in Serum Creatinine
Timepoint [4] 0 0
Baseline, Week 48

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/10/2022
Sample size
Target
Accrual to date
Final
875
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
Westmead Hospital Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [6] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [7] 0 0
Footscray Hospital - Footscray
Recruitment hospital [8] 0 0
Austin Health - Heidelberg
Recruitment hospital [9] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [10] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [11] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2137 - Concord
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
3011 - Footscray
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
3004 - Melbourne
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment postcode(s) [11] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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California
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Florida
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Sofia
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Manitoba
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Ontario
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France
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Clichy
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Paris
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France
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Strasbourg
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France
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Villejuif
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Hong Kong
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Hong Kong
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Hong Kong
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Lai Chi Kok
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Hong Kong
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Sha Tin
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Hong Kong
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Tai Po
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Hong Kong
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Tuen Mun
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Rajasthan
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Izmir
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London
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Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01940471
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01940471