An Open-Label Phase 2 Study to Evaluate Safety and Efficacy of QL-007 Tablets in Combination With Entecavir or Tenofovir in Patients With Chronic Hepatitis b Who Have Received Nucleoside (Acid) Therapy : a Multicenter, Randomized, Positive Controlled Clinical Trialcontrolled Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Entecavir Tablet
- Conditions
- Chronic Hepatitis b
- Sponsor
- Qilu Pharmaceutical Co., Ltd.
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Main index of pharmacodynamics
- Last Updated
- 6 years ago
Overview
Brief Summary
This is an open label, randomized, multi-center, comparative study. Subjects will be screened prior to study entry to establish eligibility. 60 Subjects who meet all the selection criteria will be randomly assigned to (A) QL007 200mg BID+ Tenofovir dipirofurate fumarate （TDF）300 mg QD, (B) QL007 200 mg BID+ Entecavir 0.5 mg QD, (C)TDF 300 mg QD, (D) Entecavir 0.5 mg QD.
The purpose of this study was to evaluate the efficacy and safety of QL-007 tables in combination with TDF or Entecavir in patients with chronic hepatitis b who have received nucleoside (acid) therapy, and to recommend a reasonable regimen for phase III study.
Detailed Description
The subjects received the drug treatment for a maximum of 96 weeks: divided into two stages: the first stage: 0-24 weeks as the core treatment period, 25-48 weeks as the extended treatment period. The second stage: 49-96 weeks is the extended treatment period. Stage 2: subjects in stage 1 group A and C were grouped into group E(QL-007 200 mg BID或XX mg +TDF 300 mg QD), and subjects in group B and D were grouped into group F(QL-007 200 mg BID或XX mg + Entecavir 0.5 mg QD). Subjects in group E and F entered the second stage of treatment according to 200 mg BID. After the efficacy data of the original treatment clinical trial (protocol 201) determine the optimal dose of 007, all subjects entering the second phase will receive the optimal dose of 007 and continue treatment withTDF or Entecavir tablets (007 XXmg+TDF or ETV) into the second phase 49-96 weeks of extended treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients aged 18-70 years (inclusive) with chronic HBV infection prior to baseline;
- •Subjects who have received a entecavir or tenofovir ester treatment for more than 1 year before screening ;
- •HBsAg \> 250 IU/mL and HBV DNA \< 60 IU/mL at screening period;
- •ALT≤ 2×ULN;
- •Participants must have understood and signed the ICF.
Exclusion Criteria
- •Confirmed co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV);
- •History of liver disease other than chronic hepatitis B;
- •History of Gilbert's Disease;
- •History of decompensated liver disease or any sign of decompensated liver disease at the screening period;
- •Evidence of moderate or severe fibrosis or cirrhosis;
- •Evidence of HCC or AFP \> 50 ng/ml at the screening period.
- •Any Clinical laboratory values meet the certain standards at the screening period;
- •Subjects have clinically significant, uncontrolled heart disease and/or recent cardiac event;
- •Risks of serious kidney and respiratory diseases;
- •Impaired gastrointestinal (GI) function or GI disease that may alter absorption of QL-007 as determined by the Investigator;
Arms & Interventions
Entecavir monotherapy
Entecavir tablet 0.5 mg QD
Intervention: Entecavir Tablet
QL-007 +TDF
QL-007 200 mg BID +TDF 300 mg QD
Intervention: TDF tablet
QL-007 +TDF
QL-007 200 mg BID +TDF 300 mg QD
Intervention: QL-007
QL-007 +Entecavir
QL-007 200 mg BID +Entecavir 0.5 mg QD
Intervention: Entecavir Tablet
QL-007 +Entecavir
QL-007 200 mg BID +Entecavir 0.5 mg QD
Intervention: QL-007
TDF monotherapy
TDF tablet 300 mg QD
Intervention: TDF tablet
Outcomes
Primary Outcomes
Main index of pharmacodynamics
Time Frame: 24 weeks
The change of HBsAg levels at week 24 compared to baseline
Secondary Outcomes
- The secondary pharmacodynamic index(96 weeks)
- Other evaluation indexes of pharmacodynamics exploration(96 weeks)
- To evaluate the safety of QL-007 in combination with TDF or Entecavir: incidence of adverse events(96 weeks)