Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Positive Hepatitis B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01940471
Recruitment Status : Active, not recruiting
First Posted : September 12, 2013
Results First Posted : March 30, 2017
Last Update Posted : August 26, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions HBV
Chronic HBV Infection
Interventions Drug: TAF
Drug: TDF
Drug: TAF Placebo
Drug: TDF Placebo
Enrollment 875
Recruitment Details Participants were enrolled at study sites in East Asia, Europe, North America, Australia, India, and New Zealand. The first participant was screened on 25 August 2013. The last Week 48 study visit for the primary endpoint occurred on 06 November 2015.
Pre-assignment Details 1473 participants were screened.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3) TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Period Title: Double-Blind Phase
Started 582 293
Completed 14 8
Not Completed 568 285
Reason Not Completed
Randomized but Never Treated             1             1
Withdrew Consent             13             7
Adverse Event             1             2
Lost to Follow-up             3             2
Pregnancy             2             1
Investigator's Discretion             5             0
Non-Compliance with Study Drug             1             1
Protocol-Specified Criteria             1             0
Death             1             0
Lack of Efficacy             1             0
Protocol Violation             0             1
Still in Double-Blind Phase             539             270
Period Title: Open-Label Extension
Started 14 8
Completed 0 0
Not Completed 14 8
Reason Not Completed
Still in Open-Label Extension Phase             14             8
Arm/Group Title TAF 25 mg TDF 300 mg Total
Hide Arm/Group Description TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3) TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3) Total of all reporting groups
Overall Number of Baseline Participants 581 292 873
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 581 participants 292 participants 873 participants
38  (11.0) 38  (11.7) 38  (11.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
Female 210 103 313
Male 371 189 560
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
Asian 482 232 714
Black or African American 2 3 5
Native Hawaiian or Pacific Islander 1 3 4
White 96 53 149
Other 0 1 1
Hispanic or Latino 4 2 6
Not Hispanic or Latino 573 289 862
Not Permitted 4 1 5
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
Russia 33 16 49
Romania 24 9 33
Singapore 7 2 9
Hong Kong 71 50 121
United States 33 21 54
Japan 35 11 46
United Kingdom 5 3 8
India 77 33 110
Spain 4 0 4
New Zealand 11 6 17
Canada 55 28 83
Turkey 15 11 26
Taiwan 54 29 83
South Korea 120 53 173
Poland 7 5 12
Italy 9 5 14
Australia 14 6 20
Bulgaria 4 2 6
France 3 2 5
HBV DNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 581 participants 292 participants 873 participants
7.6  (1.34) 7.6  (1.41) 7.6  (1.36)
Plasma HBV DNA Level  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
< 8 log10 IU/mL 309 150 459
≥ 8 log10 IU/mL 272 142 414
IL28B Genotype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
CC 442 210 652
CT 112 69 181
TT 23 10 33
Missing 4 3 7
[1]
Measure Description: The CC, CT, and TT alleles are different forms of the IL28b gene.
Oral Antiviral Treatment Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
Treatment Experienced 151 77 228
Treatment Naive 430 215 645
Proteinuria by Urinalysis (dipstick)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 581 participants 292 participants 873 participants
Grade 0 538 259 797
Grade 1 40 31 71
Grade 2 3 2 5
Grade 3 0 0 0
[1]
Measure Description: Urine protein was measured using the dipstick method. Grade 0 = Absent; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe
1.Primary Outcome
Title Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL
Hide Description [Not Specified]
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drugs. Participants were analyzed according to the treatment to which they were randomized.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description:
TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 & 2) or 144 weeks (per amendment 3)
Overall Number of Participants Analyzed 581 292
Measure Type: Number
Unit of Measure: percentage of participants
63.9 66.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
Comments The null hypothesis was that the TAF group is at least 10% worse than the TDF group with respect to the proportion of participants with HBV DNA < 29 IU/mL at Week 48. The alternative hypothesis was that the TAF group is less than 10% worse than the TDF group with respect to the proportion of participants with HBV DNA < 29 IU/mL at Week 48. Noninferiority was assessed using a 95% confidence interval (CI) approach, with a noninferiority margin of 10%.
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Sample sizes of 288 and 576 participants in the TDF and TAF groups, respectively, were planned to give 84% power to rule out the noninferiority margin of 10% at a 1-sided significance level of 0.025. This sample size based on the assumption that the expected difference (TAF - TDF) in the proportion of participants with HBV DNA < 29 IU/mL was 0 and the proportion of participants with HBV DNA < 29 IU/mL in the TDF group was 69%. Missing data were treated as not achieving the primary endpoint .
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-9.8 to 2.6
Estimation Comments Difference in the proportion between treatment groups and its 95% CI were calculated based on the Mantel-Haenszel (MH) proportions adjusted by baseline HBV DNA categories and oral antiviral treatment status strata.
2.Secondary Outcome
Title Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48
Hide Description [Not Specified]
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Serologically Evaluable Full Analysis Set: participants who were randomized, had received at least 1 dose of study drug, and were HBeAg positive and anti-HBe negative or had a value missing value at baseline. Participants were analyzed according to their randomized treatment group. All missing data were treated as no HBeAg seroconversion.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description:
TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Overall Number of Participants Analyzed 565 285
Measure Type: Number
Unit of Measure: percentage of participants
10.3 8.1
3.Secondary Outcome
Title Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Hip Dual-Energy X-ray Absorptiometry (DXA) Analysis Set (participants who were randomized, received at least 1 dose of study drugs, and had nonmissing baseline hip BMD values) with available data were analyzed. Participants were analyzed according to the treatment they actually received. Missing data were excluded from analysis.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description:
TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Overall Number of Participants Analyzed 537 271
Mean (Standard Deviation)
Unit of Measure: percentage change
-0.100  (2.2912) -1.715  (2.5723)
4.Secondary Outcome
Title Percent Change From Baseline in Spine BMD at Week 48
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Spine DXA Analysis Set (participants who were randomized, received at least 1 dose of study drugs, and had nonmissing baseline spine BMD values) with available data were analyzed. Participants were analyzed according to the treatment they actually received. Missing data were excluded from analysis.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description:
TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Overall Number of Participants Analyzed 543 274
Mean (Standard Deviation)
Unit of Measure: percentage change
-0.417  (2.9343) -2.294  (3.1331)
5.Secondary Outcome
Title Change From Baseline at Week 48 in Serum Creatinine
Hide Description [Not Specified]
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received. Missing data were excluded from analysis.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description:
TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Overall Number of Participants Analyzed 553 283
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.009  (0.1238) 0.026  (0.0948)
6.Other Pre-specified Outcome
Title Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48
Hide Description Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method.
Time Frame Up to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with at least 1 postbaseline urine protein value were analyzed.
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description:
TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Overall Number of Participants Analyzed 577 286
Measure Type: Number
Unit of Measure: percentage of participants
Grade 1 23.9 17.8
Grade 2 3.5 4.5
Grade 3 0 0.3
Time Frame Up to the Week 48 Data Cut
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title TAF 25 mg TDF 300 mg
Hide Arm/Group Description TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3) TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
All-Cause Mortality
TAF 25 mg TDF 300 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
TAF 25 mg TDF 300 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   22/581 (3.79%)   12/292 (4.11%) 
Blood and lymphatic system disorders     
Anaemia  1  1/581 (0.17%)  0/292 (0.00%) 
Cardiac disorders     
Angina pectoris  1  1/581 (0.17%)  0/292 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  1/581 (0.17%)  0/292 (0.00%) 
Eye disorders     
Retinal detachment  1  1/581 (0.17%)  0/292 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper  1  0/581 (0.00%)  1/292 (0.34%) 
General disorders     
Pyrexia  1  1/581 (0.17%)  0/292 (0.00%) 
Infections and infestations     
Anal abscess  1  1/581 (0.17%)  0/292 (0.00%) 
Appendicitis  1  1/581 (0.17%)  0/292 (0.00%) 
Cellulitis  1  0/581 (0.00%)  1/292 (0.34%) 
Dengue fever  1  0/581 (0.00%)  1/292 (0.34%) 
Diarrhoea infectious  1  1/581 (0.17%)  0/292 (0.00%) 
Periodontitis  1  1/581 (0.17%)  0/292 (0.00%) 
Pneumonia  1  1/581 (0.17%)  0/292 (0.00%) 
Scrub typhus  1  1/581 (0.17%)  0/292 (0.00%) 
Injury, poisoning and procedural complications     
Hand fracture  1  1/581 (0.17%)  0/292 (0.00%) 
Ligament rupture  1  1/581 (0.17%)  0/292 (0.00%) 
Limb crushing injury  1  1/581 (0.17%)  0/292 (0.00%) 
Lower limb fracture  1  0/581 (0.00%)  1/292 (0.34%) 
Spinal compression fracture  1  1/581 (0.17%)  0/292 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/581 (0.17%)  0/292 (0.00%) 
Intervertebral disc degeneration  1  1/581 (0.17%)  0/292 (0.00%) 
Spondylolisthesis  1  0/581 (0.00%)  1/292 (0.34%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastrointestinal submucosal tumour  1  1/581 (0.17%)  0/292 (0.00%) 
Hepatocellular carcinoma  1  0/581 (0.00%)  2/292 (0.68%) 
Thymoma  1  0/581 (0.00%)  1/292 (0.34%) 
Transitional cell carcinoma  1  0/581 (0.00%)  1/292 (0.34%) 
Nervous system disorders     
Basilar artery occlusion  1  1/581 (0.17%)  0/292 (0.00%) 
Dizziness  1  2/581 (0.34%)  0/292 (0.00%) 
Epilepsy  1  0/581 (0.00%)  1/292 (0.34%) 
Optic neuritis  1  0/581 (0.00%)  1/292 (0.34%) 
Syncope  1  1/581 (0.17%)  0/292 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/581 (0.17%)  0/292 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst  1  0/581 (0.00%)  1/292 (0.34%) 
Respiratory, thoracic and mediastinal disorders     
Bronchitis chronic  1  1/581 (0.17%)  0/292 (0.00%) 
Nasal septum deviation  1  1/581 (0.17%)  0/292 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TAF 25 mg TDF 300 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   195/581 (33.56%)   94/292 (32.19%) 
Gastrointestinal disorders     
Abdominal pain upper  1  19/581 (3.27%)  15/292 (5.14%) 
Diarrhoea  1  27/581 (4.65%)  15/292 (5.14%) 
General disorders     
Fatigue  1  33/581 (5.68%)  14/292 (4.79%) 
Infections and infestations     
Nasopharyngitis  1  56/581 (9.64%)  16/292 (5.48%) 
Upper respiratory tract infection  1  51/581 (8.78%)  22/292 (7.53%) 
Nervous system disorders     
Headache  1  42/581 (7.23%)  22/292 (7.53%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  37/581 (6.37%)  19/292 (6.51%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
EMail: ClinicalTrialDisclosures@gilead.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01940471    
Other Study ID Numbers: GS-US-320-0110
2013-000636-10 ( EudraCT Number )
First Submitted: August 20, 2013
First Posted: September 12, 2013
Results First Submitted: December 9, 2016
Results First Posted: March 30, 2017
Last Update Posted: August 26, 2021