Clinical trial NCT03770624: A Study to Investigate the Safety, Efficacy and PK of Multiple Doses of QL-007 in Chronic Hepatitis B Patients in CHINA
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Chronic Hepatitis b
Lead sponsor: Qilu Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-12-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
timeFrame: Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax) of QL-007 following multiple doses
timeFrame: 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
measure: The time to Cmax (tmax) of QL-007 following multiple doses
timeFrame: 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
measure: AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses
timeFrame: 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
measure: AUC0-∞ of QL-007 following multiple doses following multiple doses
timeFrame: 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
measure: t1/2 (terminal elimination half-life) of QL-007 following multiple doses
timeFrame: 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
measure: Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses
timeFrame: 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
measure: Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
timeFrame: Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
measure: adverse events (AEs)
timeFrame: From randomization up to Day 35
Other outcomes:
Locations:
city: Peking
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
References: