Phase Ⅲ Trial for Combination Treatment of PEG-Tα1 and Adefovir for HBeAg-positive Chronic Hepatitis B

Study Overview
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Brief Summary
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This trial is to assess the efficacy and safety of Polyethylene Glycol thymosin alpha1 (PEG-Tα1), a new long immunomodulator (Category 1.1 of Chemical Drugs) being developed from Hansoh Pharmaceutical of China, in combination with adefovir in HBeAg-positive patients with chronic hepatitis B.

Detailed Description
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A total of 463 HBeAg-positive patients were recruited from 33 hospitals in China, and randomized to two groups. The combination group received PEG-Tα1 (3.2 mg/ml, once a week, taken subcutaneously) and adefovir (10 mg, once daily, taken orally) for 48 weeks. The control group received placebo and adefovir. The primary endpoint was the loss of HBeAg at 48 weeks. The secondary endpoints included 1) loss of hepatitis B virus (HBV) DNA, 2) HBeAg seroconversion and 3) alanine aminotransferase (ALT) normalization etc. at week 4, 12, 24, 36 and 48. The number of CD4＋and CD8＋T cells was also determined during 48 weeks.

Official Title
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Combination Treatment of Polyethylene Glycol Thymosin alpha1 (PEG-Tα1) and Adefovir for Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B: A Multi-center Randomized, Double-blind, Parallel-controlled Phase Ⅲ Trial

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: PEG-Tα1
* Drug: Placebo to match PEG-Tα1
* Drug: Adefovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis B for more than 6 months, and didn't accept immunomodulating or anti-viral treatment within 6 months before the trial. ALT level > 2 × Upper Limit Normal (ULN). Serum bilirubin < 2 × ULN. Positive HBeAg and negative HBeAb. HBV-DNA between 1.00E＋05 IU/ml and 9.99E＋09 IU/ml. Informed Consent Form (ICF) signed. Exclusion Criteria: Hepatitis A,C,D,E or HIV infection. Autoimmune hepatitis. Hepatic cirrhosis. Serum creatinine >1.5 × ULN or Ccr <50 ml/min, Haemoglobin <110g/L (male) or <100g/L (female), Platelet<80 E＋09/L, Serum albumin ≤ 35g/L, or Serum albumin/globulin (A/G) ≤0.9, Neutrophile granulocyte <1.0 E＋09/L, Prothrombin time>ULN＋3 seconds, Cholinesterase<4000U/L. Hepatitic carcinoma or Alpha Fetal Protein (AFP) >100ng/ml . Patients with other severe diseases combined, which could affect the therapy. Patients accepted other clinical trial within 6 months before the first administrated. Thymosin allergy. Pregnant or breast feeding.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-Tα1<br>PEG-Tα1 (3.2 mg/ml, once a week, taken subcutaneously) and adefovir (10 mg, once daily, taken orally) for 48 weeks | Drug: PEG-Tα1<br>* 3.2mg/ml, once a week, taken subcutaneously<br>* Other names: Polyethylene Glycol thymosin alpha1;Drug: Adefovir<br>* 10 mg, once daily, taken orally for 48 weeks<br>|
| Placebo Comparator: Placebo to match PEG-Tα1<br>PEG-Tα1 placebo (1ml, once a week, taken subcutaneously) and adefovir (10 mg, once daily, taken orally) for 48 weeks | Drug: Placebo to match PEG-Tα1<br>* 1ml, once a week, taken subcutaneously<br>Drug: Adefovir<br>* 10 mg, once daily, taken orally for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loss of HBeAg |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loss of HBV DNA |  | week 4, 12, 24, 36 and 48 | 
| HBeAg seroconversion |  | week 4, 12, 24, 36 and 48 | 
| Alanine aminotransferase normalization |  | week 4, 12, 24, 36 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polyethylene Glycol Thymosin alpha1, Adefovir, Hepatitis B e Antigens positive