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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01940341




Registration number
NCT01940341
Ethics application status
Date submitted
20/08/2013
Date registered
12/09/2013

Titles & IDs
Public title
Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Negative 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-Negative, Chronic Hepatitis B
Secondary ID [1] 0 0
2013-000626-63
Secondary ID [2] 0 0
GS-US-320-0108
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HBeAg-negative 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
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Timepoint [1] 0 0
Baseline, Week 48
Secondary outcome [2] 0 0
Percent Change From Baseline in Spine BMD at Week 48
Timepoint [2] 0 0
Baseline, Week 48
Secondary outcome [3] 0 0
Change From Baseline in Serum Creatinine at Week 48
Timepoint [3] 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.
* Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following:

* HBeAg-negative and hepatitis B e antibody (HBeAb) 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 Baseline.
* 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
12/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2022
Sample size
Target
Accrual to date
Final
426
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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United States of America
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Florida
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United States of America
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Maryland
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United States of America
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Michigan
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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Pennsylvania
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United States of America
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Virginia
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Ontario
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France
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Lyon cedex 04
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France
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Strasbourg
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Hong Kong
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Hong Kong SAR
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Hong Kong
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Kwai Chung
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Hong Kong
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Shatin
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Hong Kong
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Tai Po
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India
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Andhra Pradesh
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India
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Delhi
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India
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Gujarat
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India
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Maharastra
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India
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Mumbai
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India
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Rajasthan
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India
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West Bengal
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India
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Chandigarh
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India
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New Delhi
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Italy
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Foggia
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Italy
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Bologna
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Italy
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Pisa
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Japan
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Fukuoka-ken
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Japan
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Fukuoka-shi
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Japan
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Nagasaki
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Japan
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Osaka
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Japan
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Kitakyushu
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Japan
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Kobe
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Japan
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Musashino
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Japan
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Nishinomiya
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Japan
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Sapporo
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Japan
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Tokyo
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Korea, Republic of
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Gyeongsangnam-do
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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New Zealand
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Auckland
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Poland
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Bialystok
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Poland
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Chorzow
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Poland
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Lodz
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Poland
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Wroclaw
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Romania
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Bucuresti
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Romania
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Constanta
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Romania
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Iasi
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Russian Federation
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Novosibirsk
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Russian Federation
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Moscow
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Russian Federation
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Saint-Petersburg
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Spain
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Barcelona
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Taiwan
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Hualien City
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Turkey
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Diyarbakri
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Turkey
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Ankara
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Turkey
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Bursa
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Turkey
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Istanbul
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Turkey
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Izmir
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United Kingdom
State/province [66] 0 0
Nottinghamshire
Country [67] 0 0
United Kingdom
State/province [67] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
18 months after study completion
Available to whom?
A secured external environment with username, password, and RSA code.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gileadclinicaltrials.com/transparency-policy/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01940341