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
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •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.
Arms & Interventions
200 mg QD
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.
Intervention: QL-007 tablet (Drug)
400 mg QD
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.
Intervention: QL-007 tablet (Drug)
600 mg QD
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.
Intervention: QL-007 tablet (Drug)
100 mg BID
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.
Intervention: QL-007 tablet (Drug)
200 mg BID
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.
Intervention: QL-007 tablet (Drug)
TDF 300 mg QD
TDF will be administered orally daily (300 mg QD) over the 28 days not request fast .
Intervention: TDF (Drug)
Outcomes
Primary Outcomes
Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- adverse events (AEs)(From randomization up to Day 35)
- 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)