Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TDF · 4 trials · 2 indications
Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.
The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (\> 19 vs ≤ 19 IU/L for females; \> 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.
| Arm | Type | Description |
|---|---|---|
| Tenofovir DF | EXPERIMENTAL | TDF plus placebo to match FTC/TDF |
| FTC/TDF | EXPERIMENTAL | FTC/TDF plus placebo to match TDF |
| TDF-TDF | EXPERIMENTAL | TDF plus ADV placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC tablet) to their treatment regimen in the open-label period. |
| ADV-TDF | ACTIVE_COMPARATOR | ADV plus TDF placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF FDC tablet) to their treatment regimen in the open-label period. |
| TDF + placebo | PLACEBO_COMPARATOR | Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| TDF + Vesatolimod 1 mg | EXPERIMENTAL | Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| TDF + Vesatolimod 2 mg | EXPERIMENTAL | Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| TDF + Vesatolimod 4 mg | EXPERIMENTAL | Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. |
| Name | Type | Description |
|---|---|---|
| TDF | DRUG | Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablet administered orally once daily |
| FTC/TDF | DRUG | Emtricitabine (FTC)/TDF 200/300 mg fixed-dose combination tablet administered orally once daily |
| TDF Placebo | DRUG | TDF placebo tablet administered orally once daily |
| FTC/TDF Placebo | DRUG | FTC/TDF placebo tablet administered orally once daily |
| ADV | DRUG | 10 mg tablet administered orally once daily |
| ADV placebo | DRUG | Tablet administered orally once daily |
| Vesatolimod | DRUG | Tablets administered orally once a week (every 7 days) for 12 doses |
| Placebo | DRUG | Placebo administered orally once a week (every 7 days) for 12 doses |
Inclusion Criteria * Chronic HBV infection, defined as positive serum HBsAg for at least 6 months * 18 through 75 years of age, inclusive * HBV DNA ≥ 10\^3 IU/mL * Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase mutation(s) known to confer resistance to lamivudine...
TDF, also known as tenofovir disoproxil fumarate, is used for the treatment of chronic hepatitis B and HIV/AIDS. In clinical trials, it has been studied as a monotherapy for chronic hepatitis B and as part of combination regimens for HIV pre-exposure prophylaxis (PrEP).
TDF is a nucleotide reverse transcriptase inhibitor that works by inhibiting the reverse transcriptase enzyme, which is essential for viral replication. It is active against both hepatitis B virus and HIV, blocking the virus from multiplying in the body.
TDF is developed by Gilead Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol GILD. Gilead has conducted multiple clinical trials evaluating TDF for chronic hepatitis B and HIV.
TDF is in Phase 3 clinical development for HIV/AIDS, with an ongoing trial evaluating its use as event-driven HIV pre-exposure prophylaxis. It has completed Phase 3 trials for chronic hepatitis B, and it is also being studied in combination with other agents.
TDF is being evaluated in an ongoing Phase 3 trial (NCT05813964) for HIV pre-exposure prophylaxis in men who have sex with men. Completed trials include NCT00116805 and NCT00117676, which compared TDF to adefovir dipivoxil for chronic hepatitis B, and NCT02579382, which studied TDF with vesatolimod.
TDF refers to tenofovir disoproxil fumarate alone, while TDF/FTC is a fixed-dose combination tablet containing TDF and emtricitabine. The combination product is used in HIV treatment and prevention, whereas TDF alone is studied for hepatitis B.