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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03180619
Ethics application status
Date submitted
6/06/2017
Date registered
8/06/2017
Date last updated
8/10/2019

Titles & IDs
Public title
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, Part B: Hepatic Impairment - Participants will receive TAF for 96 weeks.


Treatment: Drugs: TAF
25 mg tablet administered orally once daily with food

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Participants Experiencing Graded Adverse Events
Timepoint [1] 0 0
Week 24
Primary outcome [2] 0 0
Proportion of Participants Experiencing Graded Laboratory Abnormalities
Timepoint [2] 0 0
Week 24
Primary outcome [3] 0 0
Proportion of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL)
Timepoint [3] 0 0
Week 24
Secondary outcome [1] 0 0
Proportion of Participants Experiencing Graded Adverse Events at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Proportion of Participants Experiencing Graded Adverse Events at Week 96
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Proportion of Participants Experiencing Graded Laboratory Abnormalities at Week 48
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
Proportion of Participants Experiencing Graded 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 - GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age) * (body weight in kg) * (0.85 if female) divided by 72 * serum creatinine in mg/dL
Timepoint [5] 0 0
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
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
Week 96
Secondary outcome [8] 0 0
Percent Change from Baseline in Hip Bone Mineral Density (BMD) at Week 24
Timepoint [8] 0 0
Week 24
Secondary outcome [9] 0 0
Percent Change from Baseline in Hip BMD at Week 48
Timepoint [9] 0 0
Week 48
Secondary outcome [10] 0 0
Percent Change from Baseline in Hip BMD at Week 96
Timepoint [10] 0 0
Week 96
Secondary outcome [11] 0 0
Percent Change from Baseline in Spine BMD at Week 24
Timepoint [11] 0 0
Week 24
Secondary outcome [12] 0 0
Percent Change from Baseline in Spine BMD at Week 48
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Percent Change from Baseline in Spine BMD at Week 96
Timepoint [13] 0 0
Week 96
Secondary outcome [14] 0 0
Proportion 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
Proportion 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
Proportion of Participants with Plasma HBV DNA < 20 IU/mL and Target Detected (i.e. < Lower Limit of Detection (LLOD)) at Week 24
Timepoint [16] 0 0
Week 24
Secondary outcome [17] 0 0
Proportion of Participants with Plasma HBV DNA < 20 IU/mL and Target Detected (i.e. < LLOD) at Week 48
Timepoint [17] 0 0
Week 48
Secondary outcome [18] 0 0
Proportion of Participants with Plasma HBV DNA < 20 IU/mL and Target Detected (i.e. < LLOD) at Week 96
Timepoint [18] 0 0
Week 96
Secondary outcome [19] 0 0
Proportion of Participants with Plasma HBV DNA < 20 IU/mL and Target Not Detected (i.e. < LLOD) at Week 24
Timepoint [19] 0 0
Week 24
Secondary outcome [20] 0 0
Proportion of Participants with Plasma HBV DNA < 20 IU/mL and Target Not Detected (i.e. < LLOD) at Week 48
Timepoint [20] 0 0
Weeks 48
Secondary outcome [21] 0 0
Proportion of Participants with Plasma HBV DNA < 20 IU/mL and Target Not Detected (i.e. < LLOD) at Week 96
Timepoint [21] 0 0
Weeks 96
Secondary outcome [22] 0 0
Proportion of Participants with Serological Response: Loss of Hepatitis s-Antigen (HBsAg) and Seroconversion to Anti-HBs in Hepatitis B e-Antigen (HBeAg)-Positive Participants at Week 24
Timepoint [22] 0 0
Week 24
Secondary outcome [23] 0 0
Proportion of Participants with Serological Response: Loss of HBsAg and Seroconversion to Anti-HBs in HBeAg-Positive Participants at Week 48
Timepoint [23] 0 0
Week 48
Secondary outcome [24] 0 0
Proportion of Participants with Serological Response: Loss of HBsAg and Seroconversion to Anti-HBs in HBeAg-Positive Participants at Week 96
Timepoint [24] 0 0
Week 96
Secondary outcome [25] 0 0
Proportion of Participants with Serological Response: Loss of HBeAg and Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24
Timepoint [25] 0 0
Week 24
Secondary outcome [26] 0 0
Proportion of Participants with Serological Response: Loss of HBeAg and Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48
Timepoint [26] 0 0
Week 48
Secondary outcome [27] 0 0
Proportion of Participants with Serological Response: Loss of HBeAg and Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96
Timepoint [27] 0 0
Week 96
Secondary outcome [28] 0 0
Proportion of Participants with Normal Alanine Aminotransferase (ALT) at Week 24
Timepoint [28] 0 0
Week 24
Secondary outcome [29] 0 0
Proportion of Participants with Normal ALT at Week 48
Timepoint [29] 0 0
Week 48
Secondary outcome [30] 0 0
Proportion of Participants with Normal ALT at Week 96
Timepoint [30] 0 0
Week 96
Secondary outcome [31] 0 0
Proportion of Participants with Normalized ALT at Week 24
Timepoint [31] 0 0
Week 24
Secondary outcome [32] 0 0
Proportion of Participants with Normalized ALT at Week 48
Timepoint [32] 0 0
Week 48
Secondary outcome [33] 0 0
Proportion of Participants with Normalized ALT at Week 96
Timepoint [33] 0 0
Week 96
Secondary outcome [34] 0 0
Change in Fibrosis as Assessed by FibroTest® at Week 24
Timepoint [34] 0 0
Week 24
Secondary outcome [35] 0 0
Change in Fibrosis as Assessed by FibroTest® at Week 48
Timepoint [35] 0 0
Week 48
Secondary outcome [36] 0 0
Change in Fibrosis as Assessed by FibroTest® at Week 96
Timepoint [36] 0 0
Week 96
Secondary outcome [37] 0 0
Change from Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24 - CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation.
Timepoint [37] 0 0
Week 24
Secondary outcome [38] 0 0
Change from Baseline in CPT Score in Hepatically Impaired Participants at Week 48
Timepoint [38] 0 0
Week 48
Secondary outcome [39] 0 0
Change from Baseline in CPT Score in Hepatically Impaired Participants at Week 96
Timepoint [39] 0 0
Week 96
Secondary outcome [40] 0 0
Change from Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24 - MELD scores are used to assess prognosis and suitability for liver transplantation.
Timepoint [40] 0 0
Week 24
Secondary outcome [41] 0 0
Change from Baseline in MELD Score in Hepatically Impaired Participants at Week 48
Timepoint [41] 0 0
Week 48
Secondary outcome [42] 0 0
Change from Baseline in MELD Score in Hepatically Impaired Participants at Week 96
Timepoint [42] 0 0
Week 96

Eligibility
Key inclusion criteria
Key

All Participants (Parts A and B):

- Ability to understand and sign a written informed consent form; consent must be
obtained prior to initiation of study procedures

- Adult male or non-pregnant female individuals

- Documented evidence of chronic HBV infection

- ALT = 10 × upper limit of normal (ULN)

Part A Only (renal impairment):

- Maintained on TDF and/or other OAV treatment(s) for chronic hepatitis B (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

- Moderate renal impairment (30 mL/min = 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

- 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
Gender
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 HCV, HIV, or 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 g/dL

- Absolute neutrophil count < 750/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

- 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
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
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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
The primary objective of this study is to evaluate the safety and tolerability of tenofovir
alafenamide (TAF) in virologically suppressed chronic hepatitis B participants with renal
and/or hepatic impairment.

This study consists of 2 Parts. Approximately 90 renally impaired participants will be
enrolled in Part A and approximately 30 hepatically impaired participants will be enrolled in
Part B.
Trial website
https://clinicaltrials.gov/show/NCT03180619
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
Other publications