An Study to Evaluate Safety and Efficacy of QL-007 Tablets in Combination With Tenofovir in Naive Patients With Chronic Hepatitis b

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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: TDF tablet; Drug: QL-007

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anbo Xiang, PhD; Phone Number: 18815317378; Email: anbo.xiang@qilu-pharma.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Southern Hospital of Southern Medical University
      • Contact: Jinlin Hou, PhD
      • Principal Investigator: Jinlin Hou, PhD
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Junqi Niu, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QL-007 100 mg QD + TDF; QL-007 tablet 100 mg QD was combined with TDF tablet 300mg	Drug: TDF tablet; TDF tablet 300mg QD; Other Names: Tenofovir disoproxil fumarate tablet; Drug: QL-007; QL-007 tablet
Experimental: QL-007 200 mg QD + TDF; QL-007 tablets 200 mg QD were combined with TDF tablet 300mg	Drug: TDF tablet; TDF tablet 300mg QD; Other Names: Tenofovir disoproxil fumarate tablet; Drug: QL-007; QL-007 tablet
Experimental: QL-007 400 mg QD+ TDF; QL-007 tablets 400 mg QD were combined with TDF tablet 300mg	Drug: TDF tablet; TDF tablet 300mg QD; Other Names: Tenofovir disoproxil fumarate tablet; Drug: QL-007; QL-007 tablet
Experimental: QL-007 200 mg BID+ TDF; QL007 tablets 200 mg BID were combined with TDF tablet 300mg	Drug: TDF tablet; TDF tablet 300mg QD; Other Names: Tenofovir disoproxil fumarate tablet; Drug: QL-007; QL-007 tablet
Active Comparator: TDF monotherapy; TDF tablet 300mg	Drug: TDF tablet; TDF tablet 300mg QD; Other Names: Tenofovir disoproxil fumarate tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of QL-007 in combination with TDF in patients with HBeAg-positive chronic hepatitis b: HBV DNA level	The change of HBV DNA level at week 24 of treatment compared to baseline	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serological indexs	The changes of HBsAg and HBeAg level from baseline at week 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96	96 weeks
serological indexs	The percentage of subjects with HBsAg and HBeAg serological clearance and/or seroconversion at week 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96	96 weeks
Virological indexs	The changes of HBV DNA level compared to baseline at week 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96	96 weeks
Virological indexs	The rate of HBV DNA negative subjects (HBV DNA <60 IU/mL) at week 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96	96 weeks
biochemistry index	The changes of ALT at week 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96 compared to baseline	96 weeks
biochemistry index	The percentage of subjects with normal ALT level at weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84 and 96	96 weeks
Other evaluation indexes of pharmacodynamics exploration	The changes of HBV RNA and HBcrAg level compared with baseline at week 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84 and 96	96 weeks
To evaluate the tolerance of QL-007 in combination with TDF: incidence of adverse events	The incidence of adverse events	96 weeks

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Junqi Niu, PhD, The First Hospital of Jilin University; Principal Investigator: Jinlin Hou, PhD, Southern Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2019
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: HBeAg-positive chronic hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: QL-007-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No