Trial Outcomes & Findings for Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF) (NCT NCT03471624)

NCT ID: NCT03471624

Last Updated: 2023-11-18

Results Overview

To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 270 participants
• Primary outcome timeframe: Baseline, 6, 12, 18, 24 months
• Results posted on: 2023-11-18

Participant Flow

Participant milestones

Measure	Tenofovir Alafenamide for 24 Months Participants with chronic hepatitis B virus (HBV) infection receive tenofovir alafenamide (TAF) 25 mg for 24 months.
Overall Study STARTED	270
Overall Study COMPLETED	258
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF)

Baseline characteristics by cohort

Measure	Tenofovir Alafenamide for 24 Months n=270 Participants Participants with chronic HBV infection receive TAF 25 mg for 24 months.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	187 Participants n=5 Participants
Age, Categorical >=65 years	83 Participants n=5 Participants
Age, Continuous	58.1 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants
Sex: Female, Male Male	157 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	269 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	269 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment South Korea	63 Participants n=5 Participants
Region of Enrollment United States	31 Participants n=5 Participants
Region of Enrollment Japan	123 Participants n=5 Participants
Region of Enrollment Taiwan	53 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 6, 12, 18, 24 months

Population: Participants with data at each respective time point are included in the analysis.

To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV treatment.

Outcome measures

Measure	Tenofovir Alafenamide for 24 Months n=270 Participants Participants with chronic HBV infection receive TAF 25 mg for 24 months.
Number of Participants With HBV DNA <20 IU Per mL Baseline	257 Participants
Number of Participants With HBV DNA <20 IU Per mL month 6	261 Participants
Number of Participants With HBV DNA <20 IU Per mL month 12	257 Participants
Number of Participants With HBV DNA <20 IU Per mL month 18	256 Participants
Number of Participants With HBV DNA <20 IU Per mL month 24	255 Participants

SECONDARY outcome

Timeframe: Baseline, 6, 12, 18, 24 months

Population: Participants with data at each respective time point are included in the analysis.

Alanine aminotransferase (ALT) normalization is defined if ALT was less than 35 U/L for men or 25 U/L for women

Outcome measures

Measure	Tenofovir Alafenamide for 24 Months n=270 Participants Participants with chronic HBV infection receive TAF 25 mg for 24 months.
Number of Participants With Normal Alanine Aminotransferase (ALT). Baseline	203 Participants
Number of Participants With Normal Alanine Aminotransferase (ALT). month 6	212 Participants
Number of Participants With Normal Alanine Aminotransferase (ALT). month 12	197 Participants
Number of Participants With Normal Alanine Aminotransferase (ALT). month 18	203 Participants
Number of Participants With Normal Alanine Aminotransferase (ALT). month 24	203 Participants

SECONDARY outcome

Timeframe: Baseline, 6, 12, 18, 24 months

Population: Participants with data at each respective time point are included in the analysis.

To describe trends in calculated eGFR as available by local labs. Estimated glomerular filtration rates (eGFR) were calculated using the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation (eGFR [mL∕min∕1.73m2] =141 × [minimum Scr∕K, 1]α × [maximum Scr/K, 1]1.209 × 0.993age × 1.018 [if female] × 1.159 [if black]) where Scr is serum creatinine in µmol/L, K is 61.9 for females and 79.6 for males, α is -0.329 for females and -0.411 for males

Outcome measures

Measure	Tenofovir Alafenamide for 24 Months n=270 Participants Participants with chronic HBV infection receive TAF 25 mg for 24 months.
Calculated eGFR Baseline	90.2 mL/min/1.73m^2 Interval 79.0 to 99.8
Calculated eGFR month 6	90.8 mL/min/1.73m^2 Interval 76.9 to 100.0
Calculated eGFR month 12	91.2 mL/min/1.73m^2 Interval 78.0 to 101.1
Calculated eGFR month 18	91.8 mL/min/1.73m^2 Interval 79.9 to 101.7
Calculated eGFR month 24	92.1 mL/min/1.73m^2 Interval 78.8 to 101.0

SECONDARY outcome

Timeframe: Baseline, month 24

Population: Participants with data at each respective time point are included in the analysis.

To describe trends in bone mass density from baseline to end of study. Bone Mass Density(BMD) was evaluated using T-score of Lumber-spine. The T-score is a comparison of the results to a average peak bone mass of healthy young adult. 0 indicates healthy young adult's mean with a SD of 1. Normal BMD was defined with T-score of -1.0 or above; osteopenia with T-score between -1.1 and -2.4, and osteoporosis with T-score of -2.5 or below (ref). Worsened BMD was defined by upstaging of BMD class from normal to osteopenia or worse or from osteopenia to osteoporosis. Improved BMD was defined by downstaging of BMD class from osteopenia to normal or osteoporosis to osteopenia or normal.

Outcome measures

Measure	Tenofovir Alafenamide for 24 Months n=270 Participants Participants with chronic HBV infection receive TAF 25 mg for 24 months.
The Mean Bone Mass Density (T-score) Change Baseline	-1.43 T-score Standard Deviation 1.36
The Mean Bone Mass Density (T-score) Change 24 month	-1.17 T-score Standard Deviation 1.38

Adverse Events

Tenofovir Alafenamide for 24 Months

Serious events: 15 serious events

Other events: 4 other events

Deaths: 1 deaths

Serious adverse events

Measure	Tenofovir Alafenamide for 24 Months n=270 participants at risk Participants with chronic HBV infection receive TAF 25 mg for 24 months.
Hepatobiliary disorders Gallbladder carcinoma	0.37% 1/270 • Number of events 1 • Up to 24 months
Hepatobiliary disorders Hepatocellular carcinoma	1.5% 4/270 • Number of events 4 • Up to 24 months
Blood and lymphatic system disorders Non-Hodgkin's Lymphoma	0.37% 1/270 • Number of events 1 • Up to 24 months
Skin and subcutaneous tissue disorders Skin T cell Lymphoma	0.37% 1/270 • Number of events 1 • Up to 24 months
Reproductive system and breast disorders Prostate cancer	0.37% 1/270 • Number of events 1 • Up to 24 months
Reproductive system and breast disorders Breast cancer	0.37% 1/270 • Number of events 1 • Up to 24 months
Gastrointestinal disorders Rectal adenocarcinoma	0.37% 1/270 • Number of events 1 • Up to 24 months
Blood and lymphatic system disorders Myelodysplastic syndrome	0.37% 1/270 • Number of events 1 • Up to 24 months
Cardiac disorders Angina pectoris	0.37% 1/270 • Number of events 1 • Up to 24 months
Nervous system disorders Brain hemorrhage	0.37% 1/270 • Number of events 1 • Up to 24 months
Gastrointestinal disorders Hemorrhoids	0.37% 1/270 • Number of events 1 • Up to 24 months
Musculoskeletal and connective tissue disorders Left Knee osteoarthritis	0.37% 1/270 • Number of events 1 • Up to 24 months

Other adverse events

Measure	Tenofovir Alafenamide for 24 Months n=270 participants at risk Participants with chronic HBV infection receive TAF 25 mg for 24 months.
Gastrointestinal disorders Nausea	1.1% 3/270 • Number of events 3 • Up to 24 months
Musculoskeletal and connective tissue disorders Body pain	0.37% 1/270 • Number of events 1 • Up to 24 months

Additional Information

Mindie H Nguyen, Professor of Medicine, GI & Hepatology, Liver Transplant

Stanford University

Phone: 650-498-6084

Email: mindiehn@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place