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

NCT03770624 | Unknown Phase 1

• 1 other identifier: QL-007-003
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis b

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

Study Arms (6)

200 mg QD

EXPERIMENTAL

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

400 mg QD

EXPERIMENTAL

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

600 mg QD

EXPERIMENTAL

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

100 mg BID

EXPERIMENTAL

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

200 mg BID

EXPERIMENTAL

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

TDF 300 mg QD

ACTIVE COMPARATOR

TDF will be administered orally daily (300 mg QD) over the 28 days not request fast .

Drug: TDF

Interventions

QL-007 tablet DRUG

QL-007 will be administered orally daily over the 28 days under fasted state.

100 mg BID; 200 mg BID; 200 mg QD; 400 mg QD; 600 mg QD

TDF DRUG

TDF will be administered orally daily over the 28 days e.

TDF 300 mg QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: December 10, 2018
• Study Start: October 16, 2018
• Primary Completion: March 30, 2019
• Study Completion: April 30, 2019
• Last Updated: December 10, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)