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

• ClinicalTrials.gov Identifier: NCT03770624
• Recruitment Status: Unknown
• First Posted: December 10, 2018
• Last Update Posted: December 10, 2018
• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Qilu Pharmaceutical Co., Ltd.

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:

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 (Clinical Trial)
• Estimated 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: October 16, 2018
• Estimated Primary Completion Date: March 30, 2019
• Estimated Study Completion Date: April 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 :

1. 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 Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China, Beijing

Peking University First Hospital; Recruiting

Peking, Beijing, China, 100034

Contact: Guiqiang Wang, Dr 13911405123 John131212@hotmail.com

Sponsors and Collaborators

Qilu Pharmaceutical Co., Ltd.

More Information

• Responsible Party: Qilu Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03770624
• Other Study ID Numbers: QL-007-003
• First Posted: December 10, 2018
• Last Update Posted: December 10, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections