Combination of ETV, TQ-A3334 and TQ-B2450 for CHB (Neptune Study)

Study Overview
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Brief Summary
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This study is a single-center, randomized, prospective, open-label Phase 2 Clinical trial to evaluate efficacy and safety of ETV and TQ-A3334 combinated with/without inhibitor of TQ-B2450 versus ETV alone in chronic hepatitis B patients. Patients were randomized to one of 3 different antiviral treatment.

Official Title
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New Combination of ETV, TQ-A3334 and TQ-B2450 for the Treatment of Chronic Hepatitis B Virus Infection

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: ETV
* Drug: TQ-A3334
* Drug: TQ-B2450


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients from 18 to 65 years of age; Chronic hepatitis B infection Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug; Agree to participate in the study and sign the patient informed consent. Exclusion Criteria: Patients who had NAs resistance; Other antiviral, anti-neoplastic or immunomodulatory treatment; Women with ongoing pregnancy or breast-feeding; Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV); ALT >10 ULN; LSM >9kPa ; History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia); Signs or symptoms of hepatocellular carcinoma; Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening; Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men; Serum creatinine level > 1.5 ULN in screening period. Phosphorus < 0.65 mmol/L; ANA > 1:100; History of severe psychiatric disease; History of a severe seizure disorder or current anticonvulsant use; History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.); History of chronic pulmonary disease associated with functional limitation; Diseases that IFN and Nucleotides or nucleosides are not suitable.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Naive:ETV<br>Entecavir 0.5 mg po daily for 24 weeks in naive patients | Drug: ETV<br>* entecavir 0.5 mg qd<br>|
| Experimental: Naive:ETV+TQ-A3334<br>Entecavir 0.5 mg po daily plus TQ-A3334 for 24 weeks in naive patients | Drug: ETV<br>* entecavir 0.5 mg qd<br>Drug: TQ-A3334<br>* TQ-A3334 po qw<br>|
| Experimental: Naive:ETV+TQ-A3334+TQ-B2450<br>Entecavir 0.5 mg po daily plus TQ-A3334 plus inhibitor of TQ-B2450 for 24 weeks in naive patients | Drug: ETV<br>* entecavir 0.5 mg qd<br>Drug: TQ-A3334<br>* TQ-A3334 po qw<br>Drug: TQ-B2450<br>* TQ-B2450 q3w iv<br>|
| Active Comparator: Experienced:ETV<br>Entecavir 0.5 mg po daily for 24 weeks in treatment experienced patients | Drug: ETV<br>* entecavir 0.5 mg qd<br>|
| Experimental: Experienced:ETV+TQ-A3334<br>Entecavir 0.5 mg po daily plus TQ-A3334 for 24 weeks in treatment experienced patients | Drug: ETV<br>* entecavir 0.5 mg qd<br>Drug: TQ-A3334<br>* TQ-A3334 po qw<br>|
| Experimental: Experienced:ETV+TQ-A3334+TQ-B2450<br>Entecavir 0.5 mg po daily plus TQ-A3334 plus TQ-B2450 for 24 weeks in treatment experienced patients | Drug: ETV<br>* entecavir 0.5 mg qd<br>Drug: TQ-A3334<br>* TQ-A3334 po qw<br>Drug: TQ-B2450<br>* TQ-B2450 q3w iv<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HBsAg quantification at week 24 | HBsAg quantification are measured | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBsAg loss rates at week 24 | HBsAg loss rates are measured | week 24 | 
| HBsAg seroconversion rates at week 24 | HBsAg seroconversion rates are measured | week 24 | 
| HBeAg loss rates at week 24 | HBeAg loss rates are measured | week 24 | 
| HBeAg seroconversion rates at week 24 | HBeAg seroconversion rates are measured | week 24 | 
| HBV DNA<20IU/mL rates at week 24 | HBV DNA<20IU/mL rates are measured | week 24 |