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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
Date last updated
25/09/2023

Titles & IDs
Public title
Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are 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
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Manitoba
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
France
State/province [13] 0 0
Lyon cedex 04
Country [14] 0 0
France
State/province [14] 0 0
Strasbourg
Country [15] 0 0
Hong Kong
State/province [15] 0 0
Hong Kong SAR
Country [16] 0 0
Hong Kong
State/province [16] 0 0
Kwai Chung
Country [17] 0 0
Hong Kong
State/province [17] 0 0
Shatin
Country [18] 0 0
Hong Kong
State/province [18] 0 0
Tai Po
Country [19] 0 0
India
State/province [19] 0 0
Andhra Pradesh
Country [20] 0 0
India
State/province [20] 0 0
Delhi
Country [21] 0 0
India
State/province [21] 0 0
Gujarat
Country [22] 0 0
India
State/province [22] 0 0
Maharastra
Country [23] 0 0
India
State/province [23] 0 0
Mumbai
Country [24] 0 0
India
State/province [24] 0 0
Rajasthan
Country [25] 0 0
India
State/province [25] 0 0
West Bengal
Country [26] 0 0
India
State/province [26] 0 0
Chandigarh
Country [27] 0 0
India
State/province [27] 0 0
New Delhi
Country [28] 0 0
Italy
State/province [28] 0 0
Foggia
Country [29] 0 0
Italy
State/province [29] 0 0
Bologna
Country [30] 0 0
Italy
State/province [30] 0 0
Pisa
Country [31] 0 0
Japan
State/province [31] 0 0
Fukuoka-ken
Country [32] 0 0
Japan
State/province [32] 0 0
Fukuoka-shi
Country [33] 0 0
Japan
State/province [33] 0 0
Nagasaki
Country [34] 0 0
Japan
State/province [34] 0 0
Osaka
Country [35] 0 0
Japan
State/province [35] 0 0
Kitakyushu
Country [36] 0 0
Japan
State/province [36] 0 0
Kobe
Country [37] 0 0
Japan
State/province [37] 0 0
Musashino
Country [38] 0 0
Japan
State/province [38] 0 0
Nishinomiya
Country [39] 0 0
Japan
State/province [39] 0 0
Sapporo
Country [40] 0 0
Japan
State/province [40] 0 0
Tokyo
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Gyeongsangnam-do
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Daegu
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
Poland
State/province [45] 0 0
Bialystok
Country [46] 0 0
Poland
State/province [46] 0 0
Chorzow
Country [47] 0 0
Poland
State/province [47] 0 0
Lodz
Country [48] 0 0
Poland
State/province [48] 0 0
Wroclaw
Country [49] 0 0
Romania
State/province [49] 0 0
Bucuresti
Country [50] 0 0
Romania
State/province [50] 0 0
Constanta
Country [51] 0 0
Romania
State/province [51] 0 0
Iasi
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Novosibirsk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Moscow
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Saint-Petersburg
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Taiwan
State/province [56] 0 0
Hualien City
Country [57] 0 0
Taiwan
State/province [57] 0 0
Kaohsiung
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taichung
Country [59] 0 0
Taiwan
State/province [59] 0 0
Tainan
Country [60] 0 0
Taiwan
State/province [60] 0 0
Taipei
Country [61] 0 0
Turkey
State/province [61] 0 0
Diyarbakri
Country [62] 0 0
Turkey
State/province [62] 0 0
Ankara
Country [63] 0 0
Turkey
State/province [63] 0 0
Bursa
Country [64] 0 0
Turkey
State/province [64] 0 0
Istanbul
Country [65] 0 0
Turkey
State/province [65] 0 0
Izmir
Country [66] 0 0
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
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)-negative chronic hepatitis B virus (HBV) infection.
Trial website
https://clinicaltrials.gov/study/NCT01940341
Trial related presentations / publications
Cathcart AL, Chan HL, Bhardwaj N, Liu Y, Marcellin P, Pan CQ, Shalimar, Buti M, Cox S, Parhy B, Zhou E, Martin R, Chang S, Lin L, Flaherty JF, Kitrinos KM, Gaggar A, Izumi N, Lim YS. No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01064-18. doi: 10.1128/AAC.01064-18. Print 2018 Oct.
Seto WK, Asahina Y, Brown TT, Peng CY, Stanciu C, Abdurakhmanov D, Tabak F, Nguyen TT, Chuang WL, Inokuma T, Ikeda F, Santantonio TA, Habersetzer F, Ramji A, Lau AH, Suri V, Flaherty JF, Wang H, Gaggar A, Subramanian GM, Mukewar S, Brunetto MR, Fung S, Chan HL. Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients With Chronic HBV Infection. Clin Gastroenterol Hepatol. 2018 Jun 20:S1542-3565(18)30633-5. doi: 10.1016/j.cgh.2018.06.023. Online ahead of print.
Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.
Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P; GS-US-320-0108 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):196-206. doi: 10.1016/S2468-1253(16)30107-8. Epub 2016 Sep 22. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2. doi: 10.1016/S2468-1253(16)30128-5.
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/study/NCT01940341