A Study to Investigate the Safety, Efficacy and PK of Multiple Doses of QL-007 in Chronic Hepatitis B Patients in CHINA

Study Overview
=================
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.

Official Title
-----------------
An Open-Label Phase 1b Study to Evaluate the Dose-Related Safety, Efficacy, and Pharmacokinetic Profile of Different Doses of QL-007 in Chronic Hepatitis B Patients

Conditions
-----------------
Chronic Hepatitis b

Intervention / Treatment
-----------------
* Drug: QL-007 tablet
* Drug: TDF


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 mg QD<br>Tablet QL-007 will be administered orally daily (200 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration. | Drug: QL-007 tablet<br>* QL-007 will be administered orally daily over the 28 days under fasted state.<br>|
| Experimental: 400 mg QD<br>Tablet QL-007 will be administered orally daily (400 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration. | Drug: QL-007 tablet<br>* QL-007 will be administered orally daily over the 28 days under fasted state.<br>|
| Experimental: 600 mg QD<br>Tablet QL-007 will be administered orally daily (600 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration. | Drug: QL-007 tablet<br>* QL-007 will be administered orally daily over the 28 days under fasted state.<br>|
| Experimental: 100 mg BID<br>Tablet QL-007 will be administered orally daily (100 mg BID) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration. | Drug: QL-007 tablet<br>* QL-007 will be administered orally daily over the 28 days under fasted state.<br>|
| Experimental: 200 mg BID<br>Tablet QL-007 will be administered orally daily (200 mg BID) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration. | Drug: QL-007 tablet<br>* QL-007 will be administered orally daily over the 28 days under fasted state.<br>|
| Active Comparator: TDF 300 mg QD<br>TDF will be administered orally daily (300 mg QD) over the 28 days not request fast . | Drug: TDF<br>* TDF will be administered orally daily over the 28 days e.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28 | Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days | Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of QL-007 following multiple doses | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. | 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 | 
| The time to Cmax (tmax) of QL-007 following multiple doses | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. | 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 | 
| AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. | 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 | 
| AUC0-∞ of QL-007 following multiple doses following multiple doses | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. | 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 | 
| t1/2 (terminal elimination half-life) of QL-007 following multiple doses | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. | 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 | 
| Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses | Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28. | 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 | 
| Change in serum HBsAg from baseline at 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 | Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28 | 
| adverse events (AEs) | AEs occur during the study | From randomization up to Day 35 |