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

Chronic Hepatitis b Clinical Trial

— QL-007  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03770624
• Other study ID #: QL-007-003
• Status: Recruiting
• Phase: Phase 1
• Start date: October 16, 2018
• Est. completion date: April 30, 2019

Study information

• Verified date: June 2018
• Source: Qilu Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 30, 2019
• Est. primary completion date: March 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• QL-007 tablet
QL-007 will be administered orally daily over the 28 days under fasted state.
• TDF
TDF will be administered orally daily over the 28 days e.

Locations

Country	Name	City	State
China	Peking University First Hospital	Peking	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	AUC0-8 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
Secondary	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
Secondary	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
Secondary	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
Secondary	adverse events (AEs)	AEs occur during the study	From randomization up to Day 35