Clinical trial NCT04157699: An Study to Evaluate Safety and Efficacy of QL-007 Tablets in Combination With Tenofovir in Naive Patients With Chronic Hepatitis b
Official title: An Open-Label Phase 2 Study to Evaluate Safety and Efficacy of QL-007 Tablets in Combination With Tenofovir in Naive Patients With Chronic Hepatitis b: a Multicenter, Randomized, Positive Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Hepatitis b
Keywords: HBeAg-positive chronic hepatitis B
Lead sponsor: Qilu Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-11-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, randomized, multi-center, comparative study. Subjects will be screened prior to study entry to establish eligibility. 100 Subjects who meet all the selection criteria will be randomly assigned 1:1:1:1:1 to (A) QL007 100 mg QD+ Tenofovir dipirofurate fumarate （TDF）300 mg QD, (B) QL007 200 mg QD+ TDF 300 mg QD, (C) QL007 400 mg QD+ TDF 300 mg QD, (D) QL007 200 mg BID+ TDF 300 mg QD, (E) TDF 300 mg QD.

The purpose of this study was to evaluate the efficacy and safety of QL-007 in combination with TDF in HBeAg positive patients with chronic hepatitis b, and to recommend a reasonable regimen for phase III study.

Detailed description: The subjects received the drug treatment for a total of 96 weeks, which was divided into two stages: the first stage: 0-24 weeks as the core treatment period and 25-48 weeks as the extended treatment period. The second stage: 49-96 weeks is the extended treatment period，subjects will enter the second stage of treatment according to the dose of the first stage. When the efficacy data of the first phase determine the optimal dose of QL-007, all subjects entering the second phase will receive the optimal dose of QL-007 and continue treatment with tenofovir dipirofurate fumarate (QL-007 XX mg+TDF) for the second phase 49-96 weeks of extended treatment.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18-70 years (inclusive) with chronic HBV infection prior to baseline;
2. Positive for HBeAg;
3. Patients who had not previously received anti-HBV treatment (including nucleoside or interferon) or had not received antiviral treatment for HBV (including nucleoside or interferon) within 6 months prior to the first taking the study drug;
4. HBV DNA≥20,000 IU/mL;
5. ALT levels \> upper limit of normal value (ULN) and\<5 times ULN;
6. Participants must have understood and signed the ICF.

Exclusion Criteria:

1. Known co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV);
2. History of liver disease other than chronic hepatitis B, which may affect the judgment of the effectiveness or safety of the study drug
3. History of Gilbert's Disease;
4. History of decompensated liver disease or any sign of decompensated liver disease in the screening period;
5. Evidence of moderate or severe fibrosis or cirrhosis;
6. Evidence of HCC or AFP \> 50 ng / ml in the screening period ;
7. Any Clinical laboratory values meet certain standards in the screening period;
8. subjects have clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months);
9. Risks of serious kidney and respiratory diseases;
10. Impaired gastrointestinal (GI) function or GI disease that may alter absorption of QL-007 as determined by the Investigator;
11. Receiving medications that meet one of the following criteria and that cannot be discontinued ≥1 week prior to the start of treatment QL-007:

    * Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes;
    * Moderate or strong inhibitors or strong inducers of CYP3A4
12. Intake of any drugs that can reduce enzyme activity;
13. History of bleeding diathesis;
14. Risks of mental and nervous system diseases during screening;
15. Pregnant or lactating female subjects; Female subjects of childbearing age who were not willing to use effective contraception throughout the study period or male subjects whose partners were fertile but were not willing to use effective contraception;
16. Volunteers who took an Investigational Product within 3 months or who have been within 5 half-lives of other trial drugs before the randomization.
17. Any other condition , which in the opinion of investigator would make a patient unfit for participation in a clinical study.

Primary outcomes:
measure: To evaluate the efficacy of QL-007 in combination with TDF in patients with HBeAg-positive chronic hepatitis b: HBV DNA level
timeFrame: 24 weeks
Secondary outcomes:
measure: serological indexs
timeFrame: 96 weeks
measure: serological indexs
timeFrame: 96 weeks
measure: Virological indexs
timeFrame: 96 weeks
measure: Virological indexs
timeFrame: 96 weeks
measure: biochemistry index
timeFrame: 96 weeks
measure: biochemistry index
timeFrame: 96 weeks
measure: Other evaluation indexes of pharmacodynamics exploration
timeFrame: 96 weeks
measure: To evaluate the tolerance of QL-007 in combination with TDF: incidence of adverse events
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Southern Hospital of Southern Medical University
state: Guangdong
city: Changchun
country: China
facility: The first hospital of Jilin university
state: Jilin
Study officials:
affiliation: Southern Hospital of Southern Medical University
name: Jinlin Hou, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Junqi Niu, PhD
role: PRINCIPAL_INVESTIGATOR
References: