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

Phase 2

• Conditions: Chronic Hepatitis b
• Interventions: Drug: ETV; Drug: TQ-A3334; Drug: TQ-B2450

• Registration Number: NCT04202653
• Lead Sponsor: Tongji Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-12
• Study First Submitted: 2019-12-15
• Study First Submitted QC: 2019-12-15
• Study First Posted: 2019-12-17
• Last Update Submitted: 2019-12-17
• Last Update Posted: 2019-12-19
• Study Start: 2020-01-01
• Primary Completion: 2020-12-31
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Male and female patients from 18 to 65 years of age;
2. Chronic hepatitis B infection
3. 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;
4. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria

1. Patients who had NAs resistance;
2. Other antiviral, anti-neoplastic or immunomodulatory treatment;
3. Women with ongoing pregnancy or breast-feeding;
4. 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);
5. ALT >10 ULN;
6. LSM >9kPa ;
7. 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);
8. Signs or symptoms of hepatocellular carcinoma;
9. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
10. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
11. Serum creatinine level > 1.5 ULN in screening period.
12. Phosphorus < 0.65 mmol/L;
13. ANA > 1:100;
14. History of severe psychiatric disease;
15. History of a severe seizure disorder or current anticonvulsant use;
16. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
17. History of chronic pulmonary disease associated with functional limitation;
18. Diseases that IFN and Nucleotides or nucleosides are not suitable.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experienced:ETV	ETV	Entecavir 0.5 mg po daily for 24 weeks in treatment experienced patients
Naive:ETV+TQ-A3334	TQ-A3334	Entecavir 0.5 mg po daily plus TQ-A3334 for 24 weeks in naive patients
Naive:ETV+TQ-A3334+TQ-B2450	TQ-B2450	Entecavir 0.5 mg po daily plus TQ-A3334 plus inhibitor of TQ-B2450 for 24 weeks in naive patients
Naive:ETV	ETV	Entecavir 0.5 mg po daily for 24 weeks in naive patients
Experienced:ETV+TQ-A3334	ETV	Entecavir 0.5 mg po daily plus TQ-A3334 for 24 weeks in treatment experienced patients
Naive:ETV+TQ-A3334	ETV	Entecavir 0.5 mg po daily plus TQ-A3334 for 24 weeks in naive patients
Naive:ETV+TQ-A3334+TQ-B2450	ETV	Entecavir 0.5 mg po daily plus TQ-A3334 plus inhibitor of TQ-B2450 for 24 weeks in naive patients
Naive:ETV+TQ-A3334+TQ-B2450	TQ-A3334	Entecavir 0.5 mg po daily plus TQ-A3334 plus inhibitor of TQ-B2450 for 24 weeks in naive patients
Experienced:ETV+TQ-A3334+TQ-B2450	ETV	Entecavir 0.5 mg po daily plus TQ-A3334 plus TQ-B2450 for 24 weeks in treatment experienced patients
Experienced:ETV+TQ-A3334+TQ-B2450	TQ-B2450	Entecavir 0.5 mg po daily plus TQ-A3334 plus TQ-B2450 for 24 weeks in treatment experienced patients
Experienced:ETV+TQ-A3334+TQ-B2450	TQ-A3334	Entecavir 0.5 mg po daily plus TQ-A3334 plus TQ-B2450 for 24 weeks in treatment experienced patients
Experienced:ETV+TQ-A3334	TQ-A3334	Entecavir 0.5 mg po daily plus TQ-A3334 for 24 weeks in treatment experienced patients

Primary Outcome Measures

Name	Time	Method
Change from baseline in HBsAg quantification at week 24	week 24	HBsAg quantification are measured

Secondary Outcome Measures

Name	Time	Method
HBsAg loss rates at week 24	week 24	HBsAg loss rates are measured
HBsAg seroconversion rates at week 24	week 24	HBsAg seroconversion rates are measured
HBeAg loss rates at week 24	week 24	HBeAg loss rates are measured
HBeAg seroconversion rates at week 24	week 24	HBeAg seroconversion rates are measured
HBV DNA<20IU/mL rates at week 24	week 24	HBV DNA\<20IU/mL rates are measured