Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02979613 | Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed | PHASE3 | COMPLETED | 490 | — | — | Dec 29, 2016 | Jan 30, 2020 | Sep 14, 2020 | 39 | United States, Canada +6 |
| NCT03180619 | 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) | PHASE2 | COMPLETED | 124 | — | — | Jun 29, 2017 | Sep 4, 2020 | Sep 27, 2021 | 30 | United States, Canada +6 |
| NCT02932150 | Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection | PHASE2 | RECRUITING | 150 | — | — | Nov 1, 2016 | Oct 1, 2029 | Apr 3, 2026 | 62 | United States, Belgium +9 |
| NCT02862548 | 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 | PHASE2 | COMPLETED | 51 | — | — | Sep 16, 2016 | May 5, 2021 | Jun 8, 2022 | 1 | New Zealand |
The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
The percentage of participants with HBV DNA \< 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach.
Treatment-emergent AEs were defined as: * Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; * Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; * Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
| Arm | Type | Description |
|---|---|---|
| TAF 25 mg | EXPERIMENTAL | Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks. |
| TDF 300 mg | ACTIVE_COMPARATOR | DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks. |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | EXPERIMENTAL | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), will switch to tenofovir alafenamide (TAF) and receive TAF 25 milligram (mg) tablet once daily orally for 96 weeks. |
| Part A (Renal Impairment): End Stage Renal Disease | EXPERIMENTAL | Participants with CHB and end stage renal disease who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. |
| Part B: Hepatic Impairment | EXPERIMENTAL | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. |
| TAF (Cohort 1) | EXPERIMENTAL | Participants (12 to \< 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks |
| Placebo (Cohort 1) | PLACEBO_COMPARATOR | Participants (12 to \< 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks |
| TAF (Cohort 2 Group 1) | EXPERIMENTAL | Participants (6 to \< 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks |
| TAF (Cohort 2 Group 2) | EXPERIMENTAL | Participants (6 to \< 12 years) weighing ≥ 14 kg to \< 25 kg will receive TAF 15 mg oral granules for 24 weeks |
| TAF (Cohort 2 Group 3) | EXPERIMENTAL | Participants (2 to \< 6 years) will receive TAF for 24 weeks as follows: * weight ≥ 10 kg to \< 14 kg (7.5 mg oral granules) * weight ≥ 14 kg to \< 25 kg (15 mg oral granules) The study has reopened and recruitment is initiated only for this cohort for ≥ 10 to \< 14 kg at this time. |
| Cohort 2 Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks. |
| Open-Label TAF | EXPERIMENTAL | Following 24 weeks of blinded randomized treatment, participants will be eligible to participate in an open-label extension phase to receive TAF for an additional 216 weeks. |
| TAF | EXPERIMENTAL | TAF 25 mg once daily for 48 weeks |
| TDF-Containing Regimens | ACTIVE_COMPARATOR | TDF alone or in combination with other approved antivirals per local practice for 48 weeks |
| Optional Treatment Extension Phase | EXPERIMENTAL | After Week 48, participants will be eligible to receive TAF 25 mg once daily for an additional 144 weeks. |
| Name | Type | Description |
|---|---|---|
| TAF | DRUG | 25 mg tablet administered orally once daily |
| TDF | DRUG | 300 mg tablet administered orally once daily |
| TAF Placebo | DRUG | Tablet administered orally once daily |
| TDF Placebo | DRUG | Tablet administered orally once daily |
| Placebo | DRUG | Administered orally once daily |
| Other approved antivirals | DRUG | Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice |
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 * Adult male and non-pregnant, non-lactating females * Documented evidence of chronic hepatitis B virus (HBV) infection previously...