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

Sponsor

Qilu Pharmaceutical Co., Ltd. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03770624

Collaborator

(none)

Enrollment

Location

Arms

6.4

Anticipated Duration (Months)

9.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b	Drug: QL-007 tablet Drug: TDF	Phase 1

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 16, 2018

Anticipated Primary Completion Date :

Mar 30, 2019

Anticipated Study Completion Date :

Apr 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: QL-007 tablet QL-007 will be administered orally daily over the 28 days under fasted state.
Experimental: 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.	Drug: QL-007 tablet QL-007 will be administered orally daily over the 28 days under fasted state.
Experimental: 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.	Drug: QL-007 tablet QL-007 will be administered orally daily over the 28 days under fasted state.
Experimental: 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.	Drug: QL-007 tablet QL-007 will be administered orally daily over the 28 days under fasted state.
Experimental: 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.	Drug: QL-007 tablet QL-007 will be administered orally daily over the 28 days under fasted state.
Active Comparator: TDF 300 mg QD TDF will be administered orally daily (300 mg QD) over the 28 days not request fast .	Drug: TDF TDF will be administered orally daily over the 28 days e.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University First Hospital	Peking	Beijing	China	100034

Sponsors and Collaborators

Qilu Pharmaceutical Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Qilu Pharmaceutical Co., Ltd.

ClinicalTrials.gov Identifier:

NCT03770624

Other Study ID Numbers:

QL-007-003

First Posted:

Dec 10, 2018

Last Update Posted:

Dec 10, 2018

Last Verified:

Jun 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 10, 2018