Chronic Hepatitis b
Conditions
Brief summary
This is a randomized, open-label, positive-control, dose-escalation Phase 1b trial in 60 patients with chronic HBV infection to determine the safety, preliminary efficacy, and pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a fasted state at the following planned dose levels: 200, 400, and then 600 mg.
Detailed description
This is a randomized, open-label, positive-control, dose-escalation Phase 1b trial in 60 patients with chronic HBV infection to determine the safety, preliminary efficacy, and pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a fasted state at the following planned dose levels: 200, 400, and then 600 mg.
Interventions
DRUGQL-007 tablet
QL-007 will be administered orally daily over the 28 days under fasted state.
DRUGTDF
TDF will be administered orally daily over the 28 days e.
Sponsors
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chronic Hepatitis B infection, defined as positive test for Hepatitis B surface antigen (HBsAg) for more than 6 months prior to randomization * HBV DNA at screening greater than or equal to (\>/=) 2 × 10\^4 international units per milliliter (IU/mL) for Hepatitis B e antigen (HBeAg) positive participants, or \>/=2 × 10\^3 IU/mL for HBeAg-negative participants * ALT\> 1 x upper limit of normal (ULN) and \< 10 x upper limit of normal (ULN) * Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside therapy with the last dose ≥4 weeks prior to screening are also eligible. * Signed informed consent.
Exclusion criteria
* Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV) * Presence of autoimmune disorders * History of liver disease other than Hepatitis B * History of Gilbert's Disease * Any sign of decompensated liver disease * Known or suspected cirrhosis * Evidence of hepatocellular carcinoma * Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months) * Pregnant or lactating females * Diabetes * Alcohol or substance abuse * History of bleeding diathesis * Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator. * History of clinically significant gastrointestinal, cardiovascular, endocrine, renal, ocular, pulmonary, psychiatric or neurological disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28 | Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28 | Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The time to Cmax (tmax) of QL-007 following multiple doses | Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. |
| AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses | Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. |
| AUC0-∞ of QL-007 following multiple doses following multiple doses | Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. |
| Peak Plasma Concentration (Cmax) of QL-007 following multiple doses | Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. |
| Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses | Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. |
| Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28 | Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28 | Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days |
| adverse events (AEs) | From randomization up to Day 35 | AEs occur during the study |
| t1/2 (terminal elimination half-life) of QL-007 following multiple doses | Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. |
Countries
China
Outcome results
None listed