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

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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: ETV; Drug: TQ-A3334; Drug: TQ-B2450

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: December 15, 2019
• First Submitted That Met QC Criteria: December 15, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: TQ-A3334-II-02

Drug and device information, study documents

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