Phase 2
Completed N=124
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)
Source: ClinicalTrials.gov NCT03180619 ↗Enrolled (actual)
124
Serious AEs
24.2%
Results posted
Apr 2020
Primary outcomePrimary: Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 — 97.4; 100.0; 100.0 percentage of participants
Summary
The primary objective of this study is to evaluate the safety and tolerability and virologic response of tenofovir alafenamide (TAF) in virologically suppressed chronic hepatitis B participants with renal and/or hepatic impairment.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 |
97.4; 100.0; 100.0 | — |
| PRIMARY Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 |
53.8; 73.3; 54.8; 6.4; 13.3; 6.5 | — |
| PRIMARY Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 |
96.2; 100.0; 90.3; 11.5; 46.7; 48.4 | — |
| SECONDARY Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 |
71.8; 86.7; 71.0; 15.4; 20.0; 12.9 | — |
| SECONDARY Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 |
74.4; 100.0; 77.4; 17.9; 26.7; 25.8 | — |
| SECONDARY Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 |
96.2; 100.0; 90.3; 12.8; 40.0; 41.9 | — |
| SECONDARY Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 |
96.2; 100.0; 100.0; 15.4; 46.7; 41.9 | — |
| SECONDARY 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 |
-0.4; 1.9 | — |
| SECONDARY Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48 |
-0.5; 1.2 | — |
| SECONDARY Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96 |
1.0; -2.4 | — |
| SECONDARY Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 |
0.135; 0.322; 0.322 | — |
| SECONDARY Percent Change From Baseline in Hip BMD at Week 48 |
0.565; -1.075; -0.221 | — |
| SECONDARY Percent Change From Baseline in Hip BMD at Week 96 |
0.425; -0.834; 0.277 | — |
| SECONDARY Percent Change From Baseline in Spine BMD at Week 24 |
1.229; 0.683; 1.258 | — |
| SECONDARY Percent Change From Baseline in Spine BMD at Week 48 |
1.516; 0.016; 0.535 | — |
| SECONDARY Percent Change From Baseline in Spine BMD at Week 96 |
1.293; -0.283; -0.249 | — |
| SECONDARY Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 |
92.3; 93.3; 100.0 | — |
| SECONDARY Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 |
83.3; 86.7; 77.4 | — |
| SECONDARY Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 |
21.8; 40.0; 22.6 | — |
| SECONDARY Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 |
26.9; 26.7; 25.8 | — |
| SECONDARY Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 |
14.1; 20.0; 0 | — |
| SECONDARY Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 |
75.6; 60.0; 77.4 | — |
| SECONDARY Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 |
65.4; 66.7; 74.2 | — |
| SECONDARY Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 |
69.2; 66.7; 77.4 | — |
| SECONDARY Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 |
0.0; 6.7; 3.3 | — |
| SECONDARY Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 |
0; 0; 6.7 | — |
| SECONDARY Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 |
0; 33.3; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 |
0; 0; 0 | — |
| SECONDARY Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 |
0; 33.3; 0 | — |
| SECONDARY 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 |
92.3; 93.3; 83.9; 87.2; 93.3; 80.6 | — |
| SECONDARY Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria |
89.7; 86.7; 90.3; 87.2; 80.0; 80.6 | — |
| SECONDARY Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria |
82.1; 86.7; 71.0; 74.4; 86.7; 58.1 | — |
| SECONDARY Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria |
66.7; 50.0; 40.0; 60.0 | — |
| SECONDARY Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria |
33.3; 75.0; 60.0; 60.0 | — |
| SECONDARY Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria |
33.3; 50.0; 20.0; 50.0 | — |
| SECONDARY Change From Baseline in FibroTest® Score at Week 24 |
-0.01; -0.01; -0.05 | — |
| SECONDARY Change From Baseline in FibroTest® Score at Week 48 |
-0.03; -0.01; -0.03 | — |
| SECONDARY Change From Baseline in FibroTest® Score at Week 96 |
-0.01; 0.03; -0.02 | — |
| SECONDARY Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24 |
— | — |
| SECONDARY Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48 |
— | — |
| SECONDARY Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96 |
— | — |
| SECONDARY Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24 |
-0.6 | — |
| SECONDARY Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48 |
0.1 | — |
| SECONDARY Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96 |
-1.0 | — |
Eligibility Criteria
Key Inclusion Criteria
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] 10 × ULN
- Albumin 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.
Data sourced from ClinicalTrials.gov (NCT03180619). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.