The Effects of Adding TCM-700C on the Standard Combination Treatment for Patients With Genotype 1 Hepatitis C Infection

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effectiveness of TCM-700C as an add-on treatment to the combination drug therapy (Peginterferon α-2b plus Ribavirin) for patients with genotype 1 chronic hepatitis C infections. This will be demonstrated by a higher sustained virologic response rate, defined as the absence of detectable HCV RNA 24 weeks after the termination of combinational drug treatment, compared with the placebo add-on.

Detailed Description
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This was a randomized, double-blind, placebo controlled, parallel-group, Phase 2 study to evaluate the effects of adding a Chinese formulation (TCM-700C) on the standard combination treatment for patients with Genotype 1 hepatitis C infection. Patients were screened within 4 weeks before receive the first study drug dose. Eligible patients at baseline were stratified according to baseline HCV RNA (≤800,000 IU/ml vs >800,000 IU/ml) and randomized with an equal chance to receive either TCM-700C or placebo as an add-on to the combination drug therapy. The combination drug therapy was peginterferon α-2b (PEG-INTRON®, Schering-Plough) 1.5 micrograms/kg once weekly injection for 48 weeks plus oral ribavirin (REBETOL®, Shering-Plough) 1000mg-1200mg daily for 48 weeks. The add-on treatment of TCM-700C or placebo was given 2 tablets thrice daily for 48 weeks. During the 48 week treatment period and 24 week untreated follow-up, patients were assessed at regular intervals for safety and efficacy at weeks 2, 4, 8, 12, 16 and then every 8 weeks thereafter until study completion. Patients who prematurely discontinued test drug therapy had laboratory examination re-taken on the week patient was discontinued from study.

Official Title
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TCM-700C Phase II Trial The Effects of Adding a Chinese Formulation (TCM-700C) on the Standard Combination Treatment for Patients With Genotype 1 Hepatitis C Infection

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: TCM-700C
* Drug: Peginterferon alfa-2a
* Drug: Ribavirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV strain confirmed as genotype I; Elevated ALT (≥1.5 x upper limit of normal)during last 6 months Females of childbearing potential with a negative serum pregnancy test Subject must be willing to sign a written informed consent Subject must be willing and able to adhere to dose and visit schedule. Exclusion Criteria: Serum AFP levels > 400 ng/ml Liver biopsy within 12 months prior to study entry showed liver cirrhosis with METAVIR system fibrosis score of 3-4, or hepatocellular carcinoma (HCC); Co-infection with hepatitis B virus (HBV); Anti-HIV positive;

Ages Eligible for Study
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Minimum Age: 20 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: TCM-700C<br>an add-on drug (2 tablets/t.i.d) to conventional treatment(Peginterferon alfa-2a + ribavirin) of Hepatitis C | Drug: TCM-700C<br>* An add-on drug to conventional treatment of Hepatitis C<br>Drug: Peginterferon alfa-2a<br>* conventional treatment of Hepatitis C<br>* Other names: Peg-INTRON, Schering-Plough;Drug: Ribavirin<br>* conventional treatment of Hepatitis C<br>* Other names: Rebetol, Schering-Plough);|
| Placebo Comparator: Placebo<br>placebo add on(2 tablets/t.i.d) to conventional treatment(Peginterferon alfa-2a + ribavirin) of Hepatitis C | Drug: Peginterferon alfa-2a<br>* conventional treatment of Hepatitis C<br>* Other names: Peg-INTRON, Schering-Plough;Drug: Ribavirin<br>* conventional treatment of Hepatitis C<br>* Other names: Rebetol, Schering-Plough);Drug: Placebo<br>* Placebo, without acting ingredient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virologic Response (SVR) | SVR is defined as no detectable HCV RNA in serum of patient at Week 72, which is 24 weeks after the termination of combination drug treatment.. A subject is a sustained responder at a given week, if the subject has negative HCV RNA at that week and all the subsequent weeks through Week 72. If a patient has a missing value between visits, then the last non-missing HCV RNA is carried forward to fill in the missing value. If the patient's HCV RNA at last visit, Week 72 is missing or above the limit of detection, then the patient is a non-responder, even if all the previous visits from baseline onwards were undetectable. Serum HCV RNA will be tested using a commercially available real-time polymerase-chain-reaction (PCR) assay kit (Roche Cobas TaqMan HCV assay kit) | 24 weeks after the termination of combinational drug treatment (up to 72 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Response | undetectable HCV RNA at the end of combination drug treatment Serum HCV RNA will be tested using a commercially available real-time polymerase-chain-reaction (PCR) assay kit (Roche Cobas TaqMan HCV assay kit). | at the end of combination drug treatment (up to 48 weeks) | 
| ALT Response | An ALT response is defined as normalization of ALT at the end of combination drug treatment. (ALT normalization is defined as ALT level decreases into within the normal range) | at the end of combination drug treatment (up to 48 weeks) | 
| Sustained ALT Response | a sustained ALT response is defined as sustained normalization of ALT 24 weeks after cessation of combination drug treatment. | 24 weeks after the termination of combinational drug treatment (up to 72 weeks) | 
| Combined ALT and Virologic Response | Combined ALT and virologic response at the end of combination drug treatment. | at the end of combination drug treatment (up to 48 weeks) | 
| Immune Cell Normalization | Normalization of immune cells, CD4, CD8 and NK cells at the end of combination drug treatment (Immune cell normalization is defined as return of CD4, CD8 and NK cells to normal range) | at the end of combination drug treatment (up to 48 weeks) | 
| Immune Cell Normalization | Normalization of immune cells, CD4, CD8 and NK cells at 24 weeks after cessation of combination drug treatment. | 24 weeks after the termination of combinational drug treatment (up to 72 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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add-on treatment, botanical drug, HCV genotype 1, TCM-700C, genotype I