Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TAF · 10 trials · 9 indications
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 primary efficacy endpoint was determined by the achievement of HBV DNA \< 29 IU/mL at Week 48.
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).
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Cmax is defined as the maximum concentration of drug.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
| 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. |
| Double-Blind TAF | EXPERIMENTAL | Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 144 weeks (per amendment 3.1). |
| Double-Blind TDF | ACTIVE_COMPARATOR | TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1). |
| Open-label TAF | EXPERIMENTAL | All participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study. |
| Part 1 Sentinel Cohort (TAF) | EXPERIMENTAL | TAF + their current failing ARV regimen for 10 days in Part 1 |
| Part 1 Randomized Cohort (TAF) | EXPERIMENTAL | Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1. |
| Part 1 Randomized Cohort (Placebo) | PLACEBO_COMPARATOR | Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1. |
| Part 2 E/C/F/TAF+ATV | EXPERIMENTAL | Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a \> 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country. |
| 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. |
| 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. |
| Severe Hepatic Impairment Group | EXPERIMENTAL | Participants with severe hepatic impairment will receive a single oral dose of TAF 25 mg on Day 1. |
| Matched Normal Hepatic Function Group | ACTIVE_COMPARATOR | Participants with normal hepatic function will receive a single oral dose of TAF 25 mg on Day 1. |
| 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 | Tablets to match TAF administered orally once daily with food |
| E/C/F/TAF | DRUG | 150/150/200/10 mg STR administered orally once daily with food |
| Current failing ARV regimen | DRUG | Participants will continue taking their current ARV regimen as prescribed in Part 1. |
| ATV | DRUG | 300 mg tablet 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...
TAF (tenofovir alafenamide) is an investigational small molecule being studied for the treatment of chronic hepatitis B, including HBeAg-positive and HBeAg-negative chronic hepatitis B, as well as HIV and hepatitis B virus infections. It is being developed by Gilead Sciences for infectious disease indications.
TAF is a nucleotide reverse transcriptase inhibitor that works by inhibiting hepatitis B virus replication. It is a prodrug of tenofovir, designed to deliver the active drug more efficiently to target cells, potentially allowing for lower dosing compared to tenofovir disoproxil fumarate (TDF).
TAF is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol GILD. Gilead is conducting clinical trials to evaluate TAF for the treatment of chronic hepatitis B and other viral infections.
TAF is in Phase 3 clinical development for chronic hepatitis B. Multiple Phase 3 trials have been completed, including studies comparing TAF to tenofovir disoproxil fumarate (TDF) in patients with HBeAg-negative and HBeAg-positive chronic hepatitis B. TAF remains investigational and is not yet approved.
TAF has been studied in several clinical trials, including NCT01940341, a Phase 3 study comparing TAF to TDF in 426 patients with HBeAg-negative chronic hepatitis B. Other completed trials include NCT02296853 (pharmacokinetics in hepatic impairment), NCT02836236, and NCT02836249, both Phase 3 studies in Chinese patients with HBV.
TAF is also known as TAF/FTC 25mg/200mg fixed-dose combination tablets. This combination product contains tenofovir alafenamide and emtricitabine, and is being studied for the treatment of chronic hepatitis B and HIV. The fixed-dose combination is distinct from TAF alone but shares the same active tenofovir component.