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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01277601




Registration number
NCT01277601
Ethics application status
Date submitted
13/01/2011
Date registered
17/01/2011
Date last updated
26/08/2016

Titles & IDs
Public title
Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon a-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B
Scientific title
A Phase 4, Randomized, Open-label, Active-Controlled, Superiority Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon a-2a (Pegasys®) Versus Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon a-2a Monotherapy for 48 Weeks in Non-Cirrhotic Subjects With HBeAg-Positive or HBeAg-Negative Chronic Hepatitis B (CHB)
Secondary ID [1] 0 0
2010-024586-45
Secondary ID [2] 0 0
GS-US-174-0149
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - TDF
Treatment: Drugs - Peg-IFN

Experimental: TDF+Peg-IFN 48 Weeks - TDF plus Peg-IFN for 48 weeks

Experimental: TDF 48 Weeks + Peg-IFN 16 Weeks - TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks

Active comparator: TDF 120 Weeks - TDF monotherapy for 120 weeks

Active comparator: Peg-IFN 48 Weeks - Peg-IFN monotherapy for 48 weeks


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

Treatment: Drugs: Peg-IFN
Peg-IFN 180 µg administered via subcutaneous injection once weekly
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone
Timepoint [1] 0 0
Baseline; Week 72
Secondary outcome [1] 0 0
Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With TDF (48 Weeks) Plus Peg-IFN (16 Weeks) Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone
Timepoint [1] 0 0
Baseline; Week 72
Secondary outcome [2] 0 0
Percentage of Participants With HBsAg Loss at Weeks 96 and 120
Timepoint [2] 0 0
Baseline; Weeks 96 and 120
Secondary outcome [3] 0 0
Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120
Timepoint [3] 0 0
Baseline; Weeks 72, 96, and 120
Secondary outcome [4] 0 0
Percentage of Participants With HBeAg Loss and Seroconversion at Week 72
Timepoint [4] 0 0
Baseline; Week 72
Secondary outcome [5] 0 0
Percentage of Participants With HBeAg Loss and Seroconversion at Week 96
Timepoint [5] 0 0
Baseline; Week 96
Secondary outcome [6] 0 0
Percentage of Participants With HBeAg Loss and Seroconversion at Week 120
Timepoint [6] 0 0
Baseline; Week 120
Secondary outcome [7] 0 0
Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72
Timepoint [7] 0 0
Week 72
Secondary outcome [8] 0 0
Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 96
Timepoint [8] 0 0
Week 96
Secondary outcome [9] 0 0
Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 120
Timepoint [9] 0 0
Week 120
Secondary outcome [10] 0 0
Percentage of Participants With Normal ALT at Week 72
Timepoint [10] 0 0
Week 72
Secondary outcome [11] 0 0
Percentage of Participants With Normal ALT at Week 96
Timepoint [11] 0 0
Week 96
Secondary outcome [12] 0 0
Percentage of Participants With Normal ALT at Week 120
Timepoint [12] 0 0
Week 120
Secondary outcome [13] 0 0
Percentage of Participants Who Required Retreatment
Timepoint [13] 0 0
Up to 120 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
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
1/04/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2015
Sample size
Target
Accrual to date
Final
751
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
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
Saint George's Hospital - Kogarah
Recruitment hospital [4] 0 0
Liverpool Hospital,Gastroenterology Department - Liverpool
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment hospital [6] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [7] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 0 0
Royal Adelaide Hospital - Adelaide SA
Recruitment hospital [9] 0 0
Flinders Medical Center - Adelaide
Recruitment hospital [10] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [11] 0 0
Saint Vincents Hospital - Fitzroy
Recruitment hospital [12] 0 0
Western Hospital - Footscray
Recruitment hospital [13] 0 0
Austin Health - Heidelberg
Recruitment hospital [14] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [15] 0 0
Box Hill Hospital - Melbourne
Recruitment hospital [16] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [17] 0 0
Fremantle Hospital - Fremantle
Recruitment hospital [18] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [19] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- Kogarah
Recruitment postcode(s) [4] 0 0
- Liverpool
Recruitment postcode(s) [5] 0 0
- Westmead
Recruitment postcode(s) [6] 0 0
- Herston
Recruitment postcode(s) [7] 0 0
- Woolloongabba
Recruitment postcode(s) [8] 0 0
- Adelaide SA
Recruitment postcode(s) [9] 0 0
- Adelaide
Recruitment postcode(s) [10] 0 0
- Clayton
Recruitment postcode(s) [11] 0 0
- Fitzroy
Recruitment postcode(s) [12] 0 0
- Footscray
Recruitment postcode(s) [13] 0 0
- Heidelberg
Recruitment postcode(s) [14] 0 0
- Melbourne
Recruitment postcode(s) [15] 0 0
- Parkville
Recruitment postcode(s) [16] 0 0
- Fremantle
Recruitment postcode(s) [17] 0 0
- Nedlands
Recruitment postcode(s) [18] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Florida
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United States of America
State/province [3] 0 0
Illinois
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United States of America
State/province [4] 0 0
Louisiana
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United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
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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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Texas
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United States of America
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Utah
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United States of America
State/province [13] 0 0
Virginia
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Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
France
State/province [17] 0 0
Cedex
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Rennes Cedex 9
Country [20] 0 0
France
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Rouen
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France
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Strasbourg
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France
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Toulouse
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France
State/province [23] 0 0
Villejuif Cedex
Country [24] 0 0
Germany
State/province [24] 0 0
Rheinland-pfalz
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
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Germany
State/province [26] 0 0
Essen
Country [27] 0 0
Germany
State/province [27] 0 0
Frankfurt
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Germany
State/province [29] 0 0
Hannover
Country [30] 0 0
Germany
State/province [30] 0 0
Köln
Country [31] 0 0
Germany
State/province [31] 0 0
Leipzig
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Greece
State/province [32] 0 0
Attica
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Greece
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Patra
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Greece
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Thessaloniki
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Hong Kong
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Hong Kong
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Hong Kong
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Kowloon
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Hong Kong
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Shatin
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Hong Kong
State/province [38] 0 0
Tai Po
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India
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Andhra Pradesh
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India
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Assam
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India
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Gujarat
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India
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Karnataka
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India
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Maharashtra
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India
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New Delhi
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India
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Tamil Nadu
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India
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West Bengal
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Italy
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Cagliari
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Italy
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Milano
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Italy
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Napoli
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Italy
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Parma
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Italy
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Roma
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Italy
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Rome
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Italy
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Torino
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Korea, Republic of
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Chungcheon
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Korea, Republic of
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Gangwon-do
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Korea, Republic of
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Gyeonggi-d
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Korea, Republic of
State/province [57] 0 0
Gyeongsang
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Korea, Republic of
State/province [58] 0 0
Busan
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Korea, Republic of
State/province [59] 0 0
Goyang, Gyeonggi-Do
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Kwangjin-gu, Seoul
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Seoul
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Netherlands
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Amsterdam
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Netherlands
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Rotterdam
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Poland
State/province [64] 0 0
Lodzkie
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Poland
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Lubelskie
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Poland
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Slaskie
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Poland
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Bialystok
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Poland
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Bydgoszcz
Country [69] 0 0
Poland
State/province [69] 0 0
Krakow
Country [70] 0 0
Poland
State/province [70] 0 0
Lodz
Country [71] 0 0
Poland
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Warszawa
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Portugal
State/province [72] 0 0
Lisboa
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Portugal
State/province [73] 0 0
Porto
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Romania
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Brasov
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Romania
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Bucharest
Country [76] 0 0
Romania
State/province [76] 0 0
Bucuresti
Country [77] 0 0
Romania
State/province [77] 0 0
Sibiu
Country [78] 0 0
Romania
State/province [78] 0 0
Timisoara
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Sevilla
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Spain
State/province [84] 0 0
Vigo, Pontevedra
Country [85] 0 0
Taiwan
State/province [85] 0 0
Banciao Dist
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taoyuan
Country [87] 0 0
Taiwan
State/province [87] 0 0
Changhua
Country [88] 0 0
Taiwan
State/province [88] 0 0
Chia-Yi
Country [89] 0 0
Taiwan
State/province [89] 0 0
Hualien
Country [90] 0 0
Taiwan
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Kaohsiung
Country [91] 0 0
Taiwan
State/province [91] 0 0
Kaosiung
Country [92] 0 0
Taiwan
State/province [92] 0 0
Keelung Town/KEELUNG CITY
Country [93] 0 0
Taiwan
State/province [93] 0 0
Taichung
Country [94] 0 0
Taiwan
State/province [94] 0 0
Tainan
Country [95] 0 0
Taiwan
State/province [95] 0 0
Taipei
Country [96] 0 0
Turkey
State/province [96] 0 0
Ankara
Country [97] 0 0
Turkey
State/province [97] 0 0
Gaziantep
Country [98] 0 0
Turkey
State/province [98] 0 0
Istanbul
Country [99] 0 0
Turkey
State/province [99] 0 0
Mersin
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Birmingham, WSTMID
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Hampstead,London
Country [102] 0 0
United Kingdom
State/province [102] 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 evaluate the efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon a-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.
Trial website
https://clinicaltrials.gov/study/NCT01277601
Trial related presentations / publications
Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, Chuang WL, Lim SG, Tabak F, Mehta R, Petersen J, Foster GR, Lou L, Martins EB, Dinh P, Lin L, Corsa A, Charuworn P, Subramanian GM, Reiser H, Reesink HW, Fung S, Strasser SI, Trinh H, Buti M, Gaeta GB, Hui AJ, Papatheodoridis G, Flisiak R, Chan HL; Study 149 Investigators. Combination of Tenofovir Disoproxil Fumarate and Peginterferon alpha-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B. Gastroenterology. 2016 Jan;150(1):134-144.e10. doi: 10.1053/j.gastro.2015.09.043. Epub 2015 Oct 8.
Chan HL, Elkhashab M, Trinh H, Tak WY, Ma X, Chuang WL, Kim YJ, Martins EB, Lin L, Dinh P, Charuworn P, Foster GR, Marcellin P. Association of baseline vitamin D levels with clinical parameters and treatment outcomes in chronic hepatitis B. J Hepatol. 2015 Nov;63(5):1086-92. doi: 10.1016/j.jhep.2015.06.025. Epub 2015 Jul 2.
Public notes

Contacts
Principal investigator
Name 0 0
Belinda Jump
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/NCT01277601