A Study of TQ-A3334 Combined With Entecavir in the Treatment of Chronic Hepatitis B

Study Overview
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Brief Summary
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This is a randomized, double-blinded, placebo-controlled, phase IIa study to evaluate safety and efficacy of TQ-A3334 combined with entecavir in the untreated or HBV DNA negative subjects with Chronic Hepatitis B.

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Phase IIa Study of TQ-A3334 Combined With Entecavir in the Treatment of Untreated or HBV DNA Negative Subjects With Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: TQ-A3334
* Drug: Placebo
* Drug: Entecavir Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 18 and 65 years old ; 2. HBsAg positive at least for 6 months ; 3. HBeAg positive chronic hepatitis B, HBV DNA > 10^5 copies/ml; 4. Fibroscan ≤ 12.4 Kpa，2×ULN ≤ ALT ≤ ULN; 5. New diagnosed chronic hepatitis B subjects; Exclusion Criteria: 1.Combined with other virus infection ; 2.Has cirrhosis or hepatocellular carcinoma; 3.Has autoimmune diseases; 4.Has thyroid disease; 5.Has eye diseases; 6.Has clinically significant abnormalities/diseases ≥ grade 2; 7.Has history of chronic kidney disease, renal insufficiency, renal anemia; 8.Peripheral blood index is low; 9.Has a history of allergy to experimental drugs or their excipients; 10.Has participated in other clinical trials within 3 months; 11.Breastfeeding or pregnant women.; Men unwilling to use adequate contraceptive measures during the study; 12.According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.; 13.Has history of drug abuse in the past five years;

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQ-A3334 combined with entecavir<br>Subjects receive TQ-A3334 (1.2 mg QW) and entecavir (0.5 mg qd) in 24 weeks | Drug: TQ-A3334<br>* TQ-A3334 is a kind of TLR7 receptor agonist.<br>Drug: Entecavir Tablet<br>* Entecavir (ETV) tablet is an antiviral medication used in the treatment of hepatitis B virus (HBV) infection.<br>|
| Placebo Comparator: Placebo combined with entecavir<br>Subjects receive placebo (0 mg QW) and entecavir (0.5 mg qd) in 24 weeks | Drug: Placebo<br>* Placebo is a treatment which is designed to have no therapeutic value.<br>Drug: Entecavir Tablet<br>* Entecavir (ETV) tablet is an antiviral medication used in the treatment of hepatitis B virus (HBV) infection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Cmax is the maximum plasma concentration of TQ-A3334 or metabolite(s). | Hour 0, 5, 10, 20, 30 minutes, 1, 2 , 3 , 6 , 12, 24, 72 , 168 hours post-dose at week 1 and week 12; Hour 0 of week 4, week 7, week 9, week 11. | 
| Tmax | To characterize the pharmacokinetics of TQ-A3334 by assessment of time to reach maximum plasma concentration. | Hour 0, 5, 10, 20, 30 minutes, 1, 2 , 3 , 6 , 12, 24, 72 , 168 hours post-dose at week 1 and week 12; Hour 0 of week 4, week 7, week 9, week 11. | 
| AUC0-t | To characterize the pharmacokinetics of TQB3804 by assessment of area under the plasma concentration time curve from zero to infinity. | Hour 0, 5, 10, 20, 30 minutes, 1, 2 , 3 , 6 , 12, 24, 72 , 168 hours post-dose at week 1 and week 12; Hour 0 of week 4, week 7, week 9, week 11. | 
| Cytokine | Including IFN-α, IFN-γ, TNF-α, IL-6, IL-2, MCP-1 and so on. | Hour 0, 1.5 , 12 , 24 , 72 hours post-dose at week 1 and week 12; Hour 0 at week 7. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV biomarker | Including HBsAg, HBsAb, HBeAb, anti-HBc, HBV-DNA, HBV RNA and HBcrAg. | Day 1 pre-dose, day 84, day 168, day 336 post-dose. | 
| Lymphocyte function | Analysis of immune cell response to hepatitis B antigen after treatment. | Hour 0 pre-dose, day 56, day 84, day 168 at post-dose. |