Efficacy and Safety of Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF)-Containing Regimens in Participants With Chronic Hepatitis B Virus (HBV) Infection and Stage 2 or Greater Chronic Kidney Disease Who Have Received a Liver Transplant

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02862548
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arms: 3
• Actual Duration (Months): 55.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF)-containing regimens at Week 24 in participants with chronic hepatitis B virus (HBV) infection and Stage 2 or greater chronic kidney disease who have received a liver transplant.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: TAF; Drug: TDF; Drug: Other approved antivirals	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open Label Study to Evaluate the Efficacy and Safety of Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF)-Containing Regimens in Subjects With Chronic HBV Infection and Stage 2 or Greater Chronic Kidney Disease Who Have Received a Liver Transplant
• Actual Study Start Date: Sep 16, 2016
• Actual Primary Completion Date: Feb 8, 2018
• Actual Study Completion Date: May 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAF TAF 25 mg once daily for 48 weeks	Drug: TAF; Tablet administered orally; Other Names: Vemlidy®
Active Comparator: TDF-Containing Regimens TDF alone or in combination with other approved antivirals per local practice for 48 weeks	Drug: TDF; Tablet administered orally; Drug: Other approved antivirals; Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice
Experimental: Optional Treatment Extension Phase After Week 48, participants will be eligible to receive TAF 25 mg once daily for an additional 144 weeks.	Drug: TAF; Tablet administered orally; Other Names: Vemlidy®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) at Week 24 Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation [Baseline, Week 24]

2. Percentage of Participants With HBV DNA < 20 IU/mL at Week 24 [Week 24]

Secondary Outcome Measures

1. Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 [Baseline, Week 24]

2. Percent Change From Baseline in Hip BMD at Week 48 [Baseline, Week 48]

3. Percent Change From Baseline in Spine BMD at Week 24 [Baseline, Week 24]

4. Percent Change From Baseline in Spine BMD at Week 48 [Baseline, Week 48]

5. Change From Baseline in Serum Creatinine at Week 24 [Baseline, Week 24]

6. Change From Baseline in Serum Creatinine at Week 48 [Baseline, Week 48]

7. Change From Baseline in Serum eGFR_CKD-EPI at Week 48 [Baseline, Week 48]

8. Percentage of Participants With HBV DNA < 20 IU/mL at Week 48 [Week 48]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures

• Documented evidence of chronic HBV infection prior to transplantation

• Primary or secondary (re-transplant), liver alone or liver and kidney transplant recipient from deceased or living donor

• Liver Transplant ≥ 12 weeks prior to screening

• Maintained on TDF alone or in combination with other approved antivirals for HBV prophylaxis or treatment

• Have been on approved HBV oral antiviral (OAV) treatment for at least 12 weeks post-transplant prior to screening, with HBV DNA < lower limit of quantification (LLOQ) at screening

• Screening estimated glomerular filtration rate using the chronic kidney disease epidemiology collaboration (eGFR_CKD-EPI) < 90 ml/min/1.73m^2

• Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

• Women considered of child bearing potential must have a negative serum pregnancy test at Screening and a negative urine test at Baseline before dosing

• Must be willing and able to comply with all study requirements

Key Exclusion Criteria:

• Multi-organ transplant that includes heart or lung recipient (participants who have their liver transplant as part of a liver-kidney dual transplant are eligible to enroll)

• Participants with history of de novo or recurrent hepatocellular carcinoma (HCC) post-transplant and at screening

• Histological evidence of unresolved transplant rejection

• Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis

• Participants meeting any of the following laboratory parameters at screening:

• Alanine aminotransferase (ALT) > 10 × the upper limit of normal (ULN)

• International normalized ratio (INR) > 1.5 × ULN unless the participant is stable on anticoagulant regimen affecting INR

• Albumin < 3.0 g/dL

• Direct bilirubin ≥ 4 × ULN

• Platelet count < 50,000/mL

• Co-infection with HIV or hepatitis C virus (HCV)

• Recent (within 4 weeks of Screening) episode or infection requiring systemic antibiotics

• Use of any prohibited medications listed within 28 days of the Baseline/Day 1 visit

• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (e.g., basal cell skin cancer, etc.) or hepatocellular carcinoma. Participants under evaluation for possible malignancy are not eligible

• Significant cardiovascular, pulmonary, or neurological disease

• Use of investigational agents within 3 months of screening, unless allowed by the Sponsor

• Use of any prohibited medications

• Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance

• Known hypersensitivity to study drugs, metabolites or formulation excipients

• Lactating females or those who may wish to become pregnant during the course of the study

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Auckland City Hospital	Auckland		New Zealand

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol: Original - Jun 7, 2016
• Study Protocol: Amendment 1 - Nov 22, 2016
• Study Protocol: Amendment 2 - Mar 28, 2017
• Study Protocol: Amendment 3 - Jun 18, 2019
• Statistical Analysis Plan: Week 24 Analysis - Mar 19, 2018
• Statistical Analysis Plan: Final Analysis - Jun 11, 2021

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02862548
• Other Study ID Numbers: GS-US-320-3912; ACTRN12616000898459
• First Posted: Aug 11, 2016
• Last Update Posted: Jun 8, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Kidney Diseases; Renal Insufficiency, Chronic; Antiviral Agents

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a study site in New Zealand. The first participant was screened on 16 September 2016. The last study visit occurred on 05 May 2021.
Pre-assignment Detail	57 participants were screened.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: Tenofovir alafenamide (TAF) 25 mg tablet orally once daily for 48 weeks Open-Label Extension (OLE) Phase: TAF 25 mg tablet orally once daily for additional 144 weeks	Randomized Phase: Tenofovir disoproxil fumarate (TDF) alone or in combination with other approved antivirals per local practice for 48 weeks OLE Phase: TAF 25 mg tablet orally once daily for additional 144 weeks
Period Title: Randomized Phase (Up to Week 48)
STARTED	26	25
COMPLETED	26	24
NOT COMPLETED	0	1
Period Title: Randomized Phase (Up to Week 48)
STARTED	26	24
COMPLETED	23	23
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens	Total
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks OLE Phase: TAF 25 mg tablet orally once daily for additional 144 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks OLE Phase: TAF 25 mg tablet orally once daily for additional 144 weeks	Total of all reporting groups
Overall Participants	26	25	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (12.6)	62 (8.3)	60 (10.8)
Sex: Female, Male (Count of Participants)
Female	10 38.5%	3 12%	13 25.5%
Male	16 61.5%	22 88%	38 74.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	26 100%	25 100%	51 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	7 26.9%	10 40%	17 33.3%
Black or African American	1 3.8%	0 0%	1 2%
Native Hawaiian or Pacific Islander	15 57.7%	12 48%	27 52.9%
White	2 7.7%	3 12%	5 9.8%
Other	1 3.8%	0 0%	1 2%
Region of Enrollment (Count of Participants)
New Zealand	26 100%	25 100%	51 100%
HBV Deoxy Ribonucleic Acid (DNA) (International unit per mL (IU/mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [International unit per mL (IU/mL)]	19.0 (0.00)	19.0 (0.00)	19.0 (0.00)
eGFR by CKD-EPI Creatinine (mL/minute/1.73 square meter(m^2)) [Median (Standard Deviation) ]
Median (Standard Deviation) [mL/minute/1.73 square meter(m^2)]	52.3 (12.31)	52.4 (12.74)	52.4 (12.40)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) at Week 24 Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	25
Mean (Standard Deviation) [mL/min/1.73 m^2]	2.13 (6.011)	1.87 (6.553)

2. Primary Outcome

Title	Percentage of Participants With HBV DNA < 20 IU/mL at Week 24
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all randomized participants who have received at least 1 dose of study drug. The missing = failure approach was used.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	25
Number [percentage of participants]	100.0 384.6%	100.0 400%

3. Secondary Outcome

Title	Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Hip dual energy x-ray absorptiometry (DXA) Analysis Set included participants who were randomized and had received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	25
Mean (Standard Deviation) [percent change]	0.478 (1.6342)	0.452 (2.1380)

4. Secondary Outcome

Title	Percent Change From Baseline in Hip BMD at Week 48
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Hip DXA Analysis Set with available data were analyzed.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	23
Mean (Standard Deviation) [percent change]	1.253 (1.9774)	-0.413 (2.6361)

5. Secondary Outcome

Title	Percent Change From Baseline in Spine BMD at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Spine DXA Analysis Set included participants who were randomized and had received at least 1 dose of study drug, and had nonmissing baseline spine BMD values.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	24
Mean (Standard Deviation) [percent change]	0.799 (2.5563)	-0.188 (2.5890)

6. Secondary Outcome

Title	Percent Change From Baseline in Spine BMD at Week 48
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Spine DXA Analysis Set with available data were analyzed.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	21
Mean (Standard Deviation) [percent change]	1.454 (4.5405)	-1.082 (3.0031)

7. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	25
Mean (Standard Deviation) [mg/dL]	-0.043 (0.1434)	-0.040 (0.1623)

8. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Week 48
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	22
Mean (Standard Deviation) [mg/dL]	-0.052 (0.2233)	-0.058 (0.2158)

9. Secondary Outcome

Title	Change From Baseline in Serum eGFR_CKD-EPI at Week 48
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	22
Mean (Standard Deviation) [mL/min/1.73 m^2]	3.01 (9.385)	2.09 (9.209)

10. Secondary Outcome

Title	Percentage of Participants With HBV DNA < 20 IU/mL at Week 48
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed. The missing = failure approach was used.

Arm/Group Title	TAF 25 mg	TDF-Containing Regimens
Arm/Group Description	Randomized Phase: TAF 25 mg tablet orally once daily for 48 weeks	Randomized Phase: TDF alone or in combination with other approved antivirals per local practice for 48 weeks
Measure Participants	26	25
Number [percentage of participants]	100.0 384.6%	88.0 352%

Adverse Events

Time Frame	All-Cause Mortality: Randomization up to last follow up visit (maximum 236.7 weeks); Adverse Events: First dose date up to last dose date plus 30 days (maximum 225.9 weeks)
Adverse Event Reporting Description	All-Cause Mortality: Randomized Analysis Set included all participants who were randomized into the study. Adverse Events: Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title	Randomized Phase: TAF 25 mg		Randomized Phase: TDF-Containing Regimens		OLE Phase: TAF 25 mg From TAF		OLE Phase: TAF 25 mg From TDF
Arm/Group Description	TAF 25 mg tablet orally once daily for 48 weeks		TDF alone or in combination with other approved antivirals per local practice for 48 weeks		Participants who received TAF 25 mg in randomized phase received TAF 25 mg tablet orally once daily for additional 144 weeks in OLE phase.		Participants who received TDF alone o in combination with approved antivirals per local practice in randomized phase received TAF 25 mg tablet orally once daily for additional 144 weeks in OLE phase.
All Cause Mortality
	Randomized Phase: TAF 25 mg		Randomized Phase: TDF-Containing Regimens		OLE Phase: TAF 25 mg From TAF		OLE Phase: TAF 25 mg From TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		1/25 (4%)		2/26 (7.7%)		0/24 (0%)
Serious Adverse Events
	Randomized Phase: TAF 25 mg		Randomized Phase: TDF-Containing Regimens		OLE Phase: TAF 25 mg From TAF		OLE Phase: TAF 25 mg From TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/26 (11.5%)		7/25 (28%)		8/26 (30.8%)		8/24 (33.3%)
Blood and lymphatic system disorders
Anaemia	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Cardiac disorders
Acute myocardial infarction	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Atrial fibrillation	0/26 (0%)		0/25 (0%)		0/26 (0%)		2/24 (8.3%)
Atrial flutter	1/26 (3.8%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Cardiac arrest	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Cardiac failure congestive	1/26 (3.8%)		0/25 (0%)		0/26 (0%)		0/24 (0%)
Palpitations	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Gastrointestinal disorders
Abdominal pain	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Colitis	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Diarrhoea	0/26 (0%)		0/25 (0%)		0/26 (0%)		2/24 (8.3%)
Dysphagia	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Haematemesis	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
General disorders
Chest pain	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		1/24 (4.2%)
Pyrexia	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Hepatobiliary disorders
Biliary tract disorder	1/26 (3.8%)		0/25 (0%)		0/26 (0%)		0/24 (0%)
Cholangitis	1/26 (3.8%)		2/25 (8%)		2/26 (7.7%)		1/24 (4.2%)
Cholangitis acute	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Hepatic failure	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Hepatic function abnormal	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Hepatic infarction	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Portal vein thrombosis	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Immune system disorders
Transplant rejection	1/26 (3.8%)		0/25 (0%)		0/26 (0%)		0/24 (0%)
Infections and infestations
Abscess neck	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Biliary sepsis	0/26 (0%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Cellulitis	0/26 (0%)		1/25 (4%)		2/26 (7.7%)		1/24 (4.2%)
Cytomegalovirus colitis	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Disseminated cryptococcosis	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Disseminated tuberculosis	0/26 (0%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Disseminated varicella zoster virus infection	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Escherichia urinary tract infection	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Gastroenteritis	1/26 (3.8%)		0/25 (0%)		0/26 (0%)		0/24 (0%)
Gastroenteritis viral	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Infective exacerbation of chronic obstructive airways disease	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Liver abscess	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Lower respiratory tract infection	2/26 (7.7%)		0/25 (0%)		1/26 (3.8%)		2/24 (8.3%)
Osteomyelitis fungal	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Parainfluenzae virus infection	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Pneumonia	0/26 (0%)		1/25 (4%)		2/26 (7.7%)		0/24 (0%)
Pseudomonal bacteraemia	0/26 (0%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Pulmonary tuberculosis	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Rhinovirus infection	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Sialoadenitis	0/26 (0%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Upper respiratory tract infection	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		1/24 (4.2%)
Urosepsis	0/26 (0%)		0/25 (0%)		0/26 (0%)		2/24 (8.3%)
Viral infection	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Injury, poisoning and procedural complications
Complications of transplanted liver	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Fall	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Procedural pain	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Rib fracture	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Investigations
Liver function test abnormal	1/26 (3.8%)		0/25 (0%)		0/26 (0%)		0/24 (0%)
Metabolism and nutrition disorders
Fluid overload	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma	0/26 (0%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Lung adenocarcinoma	0/26 (0%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Renal and urinary disorders
Acute kidney injury	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		4/24 (16.7%)
Nephrolithiasis	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Renal impairment	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		1/24 (4.2%)
Ureterolithiasis	0/26 (0%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Pleural effusion	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Pneumothorax	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Pulmonary hypertension	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Randomized Phase: TAF 25 mg		Randomized Phase: TDF-Containing Regimens		OLE Phase: TAF 25 mg From TAF		OLE Phase: TAF 25 mg From TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/26 (73.1%)		17/25 (68%)		22/26 (84.6%)		21/24 (87.5%)
Eye disorders
Cataract	0/26 (0%)		2/25 (8%)		2/26 (7.7%)		2/24 (8.3%)
Gastrointestinal disorders
Abdominal distension	3/26 (11.5%)		1/25 (4%)		0/26 (0%)		0/24 (0%)
Abdominal pain	1/26 (3.8%)		1/25 (4%)		2/26 (7.7%)		2/24 (8.3%)
Constipation	2/26 (7.7%)		1/25 (4%)		2/26 (7.7%)		0/24 (0%)
Diarrhoea	2/26 (7.7%)		2/25 (8%)		1/26 (3.8%)		2/24 (8.3%)
Nausea	1/26 (3.8%)		0/25 (0%)		2/26 (7.7%)		1/24 (4.2%)
Vomiting	3/26 (11.5%)		0/25 (0%)		1/26 (3.8%)		1/24 (4.2%)
General disorders
Fatigue	2/26 (7.7%)		0/25 (0%)		1/26 (3.8%)		0/24 (0%)
Influenza like illness	2/26 (7.7%)		5/25 (20%)		1/26 (3.8%)		2/24 (8.3%)
Pyrexia	3/26 (11.5%)		3/25 (12%)		0/26 (0%)		0/24 (0%)
Infections and infestations
Influenza	1/26 (3.8%)		0/25 (0%)		0/26 (0%)		2/24 (8.3%)
Lower respiratory tract infection	0/26 (0%)		0/25 (0%)		2/26 (7.7%)		1/24 (4.2%)
Upper respiratory tract infection	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		2/24 (8.3%)
Urinary tract infection	0/26 (0%)		0/25 (0%)		2/26 (7.7%)		1/24 (4.2%)
Investigations
Bone density decreased	3/26 (11.5%)		1/25 (4%)		1/26 (3.8%)		1/24 (4.2%)
Metabolism and nutrition disorders
Diabetes mellitus	2/26 (7.7%)		0/25 (0%)		0/26 (0%)		0/24 (0%)
Vitamin D deficiency	0/26 (0%)		0/25 (0%)		0/26 (0%)		3/24 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/26 (0%)		2/25 (8%)		5/26 (19.2%)		1/24 (4.2%)
Back pain	4/26 (15.4%)		1/25 (4%)		1/26 (3.8%)		1/24 (4.2%)
Myalgia	0/26 (0%)		0/25 (0%)		4/26 (15.4%)		0/24 (0%)
Nervous system disorders
Dizziness	1/26 (3.8%)		0/25 (0%)		2/26 (7.7%)		2/24 (8.3%)
Headache	4/26 (15.4%)		2/25 (8%)		0/26 (0%)		0/24 (0%)
Lethargy	2/26 (7.7%)		2/25 (8%)		2/26 (7.7%)		3/24 (12.5%)
Psychiatric disorders
Insomnia	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		2/24 (8.3%)
Renal and urinary disorders
Acute kidney injury	0/26 (0%)		0/25 (0%)		2/26 (7.7%)		1/24 (4.2%)
Nephrolithiasis	0/26 (0%)		0/25 (0%)		0/26 (0%)		2/24 (8.3%)
Nocturia	0/26 (0%)		0/25 (0%)		0/26 (0%)		2/24 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	4/26 (15.4%)		2/25 (8%)		5/26 (19.2%)		3/24 (12.5%)
Dyspnoea	0/26 (0%)		0/25 (0%)		1/26 (3.8%)		2/24 (8.3%)
Oropharyngeal pain	0/26 (0%)		2/25 (8%)		0/26 (0%)		1/24 (4.2%)
Rhinorrhoea	2/26 (7.7%)		0/25 (0%)		0/26 (0%)		1/24 (4.2%)
Skin and subcutaneous tissue disorders
Pruritus	2/26 (7.7%)		1/25 (4%)		3/26 (11.5%)		0/24 (0%)
Skin lesion	0/26 (0%)		1/25 (4%)		0/26 (0%)		2/24 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years