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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03180619




Registration number
NCT03180619
Ethics application status
Date submitted
6/06/2017
Date registered
8/06/2017

Titles & IDs
Public title
Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) From Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV)
Scientific title
A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) From Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV) in Virologically Suppressed Chronic Hepatitis B Subjects With Renal and/or Hepatic Impairment
Secondary ID [1] 0 0
2016-004625-16
Secondary ID [2] 0 0
GS-US-320-4035
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 - TAF

Experimental: Part A (Renal Impairment): Moderate or Severe Renal Impairment - Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), will switch to tenofovir alafenamide (TAF) and receive TAF 25 milligram (mg) tablet once daily orally for 96 weeks.

Experimental: Part A (Renal Impairment): End Stage Renal Disease - Participants with CHB and end stage renal disease who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks.

Experimental: Part B: Hepatic Impairment - Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks.


Treatment: Drugs: TAF
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 Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24
Timepoint [1] 0 0
Week 24
Primary outcome [2] 0 0
Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24
Timepoint [2] 0 0
Week 24
Primary outcome [3] 0 0
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24
Timepoint [3] 0 0
Week 24
Secondary outcome [1] 0 0
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96
Timepoint [4] 0 0
Week 96
Secondary outcome [5] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48
Timepoint [6] 0 0
Baseline, Week 48
Secondary outcome [7] 0 0
Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96
Timepoint [7] 0 0
Baseline, Week 96
Secondary outcome [8] 0 0
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Percent Change From Baseline in Hip BMD at Week 48
Timepoint [9] 0 0
Baseline, Week 48
Secondary outcome [10] 0 0
Percent Change From Baseline in Hip BMD at Week 96
Timepoint [10] 0 0
Baseline, Week 96
Secondary outcome [11] 0 0
Percent Change From Baseline in Spine BMD at Week 24
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Percent Change From Baseline in Spine BMD at Week 48
Timepoint [12] 0 0
Baseline, Week 48
Secondary outcome [13] 0 0
Percent Change From Baseline in Spine BMD at Week 96
Timepoint [13] 0 0
Baseline, Week 96
Secondary outcome [14] 0 0
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48
Timepoint [14] 0 0
Weeks 48
Secondary outcome [15] 0 0
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96
Timepoint [15] 0 0
Weeks 96
Secondary outcome [16] 0 0
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (= Lower Limit of Detection [LLOD]) at Week 24
Timepoint [16] 0 0
Week 24
Secondary outcome [17] 0 0
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (= LLOD) at Week 48
Timepoint [17] 0 0
Week 48
Secondary outcome [18] 0 0
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (= LLOD) at Week 96
Timepoint [18] 0 0
Week 96
Secondary outcome [19] 0 0
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24
Timepoint [19] 0 0
Week 24
Secondary outcome [20] 0 0
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48
Timepoint [20] 0 0
Weeks 48
Secondary outcome [21] 0 0
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96
Timepoint [21] 0 0
Weeks 96
Secondary outcome [22] 0 0
Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24
Timepoint [22] 0 0
Week 24
Secondary outcome [23] 0 0
Percentage of Participants With Serological Response: Loss of HBsAg at Week 48
Timepoint [23] 0 0
Week 48
Secondary outcome [24] 0 0
Percentage of Participants With Serological Response: Loss of HBsAg at Week 96
Timepoint [24] 0 0
Week 96
Secondary outcome [25] 0 0
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24
Timepoint [25] 0 0
Week 24
Secondary outcome [26] 0 0
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48
Timepoint [26] 0 0
Week 48
Secondary outcome [27] 0 0
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96
Timepoint [27] 0 0
Week 96
Secondary outcome [28] 0 0
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24
Timepoint [28] 0 0
Week 24
Secondary outcome [29] 0 0
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48
Timepoint [29] 0 0
Week 48
Secondary outcome [30] 0 0
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96
Timepoint [30] 0 0
Week 96
Secondary outcome [31] 0 0
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24
Timepoint [31] 0 0
Week 24
Secondary outcome [32] 0 0
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48
Timepoint [32] 0 0
Week 48
Secondary outcome [33] 0 0
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96
Timepoint [33] 0 0
Week 96
Secondary outcome [34] 0 0
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria
Timepoint [34] 0 0
Week 24
Secondary outcome [35] 0 0
Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria
Timepoint [35] 0 0
Week 48
Secondary outcome [36] 0 0
Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria
Timepoint [36] 0 0
Week 96
Secondary outcome [37] 0 0
Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria
Timepoint [37] 0 0
Week 24
Secondary outcome [38] 0 0
Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria
Timepoint [38] 0 0
Week 48
Secondary outcome [39] 0 0
Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria
Timepoint [39] 0 0
Week 96
Secondary outcome [40] 0 0
Change From Baseline in FibroTest® Score at Week 24
Timepoint [40] 0 0
Baseline, Week 24
Secondary outcome [41] 0 0
Change From Baseline in FibroTest® Score at Week 48
Timepoint [41] 0 0
Baseline, Week 48
Secondary outcome [42] 0 0
Change From Baseline in FibroTest® Score at Week 96
Timepoint [42] 0 0
Week 96
Secondary outcome [43] 0 0
Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24
Timepoint [43] 0 0
Baseline, Week 24
Secondary outcome [44] 0 0
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48
Timepoint [44] 0 0
Baseline, Week 48
Secondary outcome [45] 0 0
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96
Timepoint [45] 0 0
Baseline, Week 96
Secondary outcome [46] 0 0
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24
Timepoint [46] 0 0
Baseline, Week 24
Secondary outcome [47] 0 0
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48
Timepoint [47] 0 0
Baseline, Week 48
Secondary outcome [48] 0 0
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96
Timepoint [48] 0 0
Baseline, Week 96

Eligibility
Key inclusion criteria
Key

All Participants (Parts A and B):

* Adult male or non-pregnant female individuals
* Documented evidence of chronic HBV infection
* Alanine aminotransferase (ALT) = 10 × upper limit of normal (ULN)

Part A Only (renal impairment):

* Maintained on TDF and/or other OAV treatment(s) for CHB for at least 48 weeks and with viral suppression (HBV deoxyribonucleic acid [DNA] < lower limit of quantitation [LLOQ]) for = 6 months prior to screening

* All individuals must have HBV DNA < 20 International units per milliliter (IU/mL) at screening by central laboratory
* Both Hepatitis B e-Antigen (HBeAg) positive and negative individuals are eligible to participate
* Moderate renal impairment (30 milliliters per minute [mL/min] = estimated glomerular filtration rate by the cockcroft-gault formula [eGFRcg] = 59 mL/min), severe renal impairment (15 mL/min = eGFRcg < 30 mL/min) or end stage renal disease (ESRD) (eGFR < 15 mL/min) maintained on hemodialysis (HD)
* Stable renal function (for participants with moderate or severe impairment): serum creatinine measured at least once within three months prior to screening. The measurement difference between the value measured within three months prior to screening versus the screening value must be = 25% of the screening value

Part B Only (hepatic impairment):

* Maintained on TDF and/or other OAV(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA < LLOQ) for = 6 months prior to screening

* All individuals must have HBV DNA < 20 IU/mL at screening by central laboratory
* Both HBeAg positive and negative individuals are eligible to participate
* Child-pugh-turcotte (CPT) score of 7-12 (inclusive) OR a past history of CPT score = 7 and any CPT score = 12 at screening
* eGFRCG = 30 mL/min using the Cockcroft-Gault equation

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
All Individuals (Parts A & B):

* Women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
* 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 (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)
* Prior Interferon (IFN) use within 6 months of screening
* Evidence of hepatocellular carcinoma
* Received solid organ or bone marrow transplant
* Significant cardiovascular, pulmonary, or neurological disease
* Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Individuals under evaluation for possible malignancy are not eligible
* Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion
* Known hypersensitivity to study drugs, metabolites, or formulation excipients
* Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.

Part A Only (Renal Impairment):

* Current or historical evidence of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)
* Abnormal hematological and biochemical parameters, including:

* Hemoglobin < 9 grams per deciliter (g/dL)
* Absolute neutrophil count < 750/cubic millimeter (mm^3)
* Platelets = 50,000/mm^3
* Aspartate aminotransferase (AST) > 10 × ULN
* Albumin < 3.0 g/dL
* Total bilirubin > 2.5 × ULN
* International normalized ratio of prothrombin time (INR) > 1.5 × ULN (unless stable on anticoagulant regimen)
* Individuals with ESRD (i.e. eGFRcg < 15 mL/min) not on HD, or those on other forms of renal replacement therapy (i.e. peritoneal dialysis)

Part B Only (Hepatic Impairment):

* Active variceal bleeding within 6 months or prior placement of a portosystemic shunt (such as transjugular intrahepatic portosystemic shunt [TIPS])
* History of hepatorenal syndrome, hepatopulmonary syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 6 months of screening
* Grade 2 hepatic encephalopathy at screening
* Model for end-stage liver disease (MELD) score = 30
* Abnormal hematological and biochemical parameters, including

* Absolute neutrophil count < 750/mm^3
* Platelets < 30,000/mm^3
* Hemoglobin < 8.0 g/dL

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
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
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Washington
Country [4] 0 0
Canada
State/province [4] 0 0
Calgary
Country [5] 0 0
Canada
State/province [5] 0 0
Montreal
Country [6] 0 0
Canada
State/province [6] 0 0
Toronto
Country [7] 0 0
Canada
State/province [7] 0 0
Vancouver
Country [8] 0 0
Hong Kong
State/province [8] 0 0
NT
Country [9] 0 0
Hong Kong
State/province [9] 0 0
Kowloon
Country [10] 0 0
Hong Kong
State/province [10] 0 0
Tai Po
Country [11] 0 0
Italy
State/province [11] 0 0
Milan
Country [12] 0 0
Italy
State/province [12] 0 0
Bologna
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Busan
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
New Zealand
State/province [15] 0 0
Auckland
Country [16] 0 0
Taiwan
State/province [16] 0 0
Changhua
Country [17] 0 0
Taiwan
State/province [17] 0 0
Chiayi City
Country [18] 0 0
Taiwan
State/province [18] 0 0
Kaohsiung City
Country [19] 0 0
Taiwan
State/province [19] 0 0
Kaohsiung
Country [20] 0 0
Taiwan
State/province [20] 0 0
Taichung
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taipei
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taoyuan City
Country [23] 0 0
United Kingdom
State/province [23] 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.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-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.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy


What supporting documents are/will be available?

Results publications and other study-related documents