The Effects of Adding TCM-700C on the Standard Combination Treatment for HCV Genotype 1 Patients(Phase III)

Study Overview
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Brief Summary
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This is a randomized, double blind, multi-center, placebo controlled, three parallel arms, Phase IIb/III clinical study to evaluate the effects of adding a TCM-700C with a low or high dose onto the combination treatment (PegIFN plus RBV) for subjects with naive genotype 1 HCV infection. 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 combination treatment, compared with the placebo add-on.

Detailed Description
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Eligible subjects with written informed consent will be stratified according to their baseline HCV RNA (≤800,000 IU/mL versus>800,000 IU/mL), stage of liver fibrosis (METAVIR system fibrosis score of 0 1 versus 2 3). During the 48 week Treatment Period and 24 week Follow up Period, subjects will be assessed at regular intervals for efficacy and safety at Weeks 2, 4, 8, 12, 16 and then every 8 weeks thereafter until study completion. If possible, subjects who prematurely discontinue the study during the Treatment Period will have samples taken for hematology, biochemistry and urinalysis in the same week of discontinuation as well as 24 weeks after discontinuation.

Official Title
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A Phase III, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Effects of Adding TCM-700C,Botanical Drug, on the Standard Treatment (Peginterferon and Ribavirin) for Subjects With Naive Genotype 1 Hepatitis C Infection

Conditions
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Chronic Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects who are 20 to 65 years old (inclusive), of either gender and in any ethnical group in Asia. Chronic hepatitis C, positive with both antibody to hepatitis C virus (anti HCV) and HCV RNA assays. Confirmed HCV genotype 1. Subjects who are indicated to have combination treatment of PegIFNα 2a and RBV at the discretion of the investigator. All fertile males and females receiving RBV must be using two forms of effective contraception during treatment with study drugs and 6 months post treatment completion. Subjects must voluntarily give written informed consent indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Subjects must be able to comply with the assessments during the study. Subjects must be able to understand study QoL questionnaires. Exclusion Criteria: Prior treatment with any IFN α or any medicines that contain Cordyceps. Prior treatment of hepatitis C with any other antiviral or immune modulators. Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study. Subjects diagnosed with hepatocellular carcinoma (HCC) by biopsy or α fetoprotein (AFP) serology and radiology (helical computed tomography [CT] and/or magnetic resonance imaging [MRI]) within 5 years of signing the informed consent form. Evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy). History or evidence of other liver diseases other than chronic HCV infection. Subjects with known allergy or hypersensitivity to any ingredient of the study drug or placebo. Pregnant, planning on becoming pregnant, or breastfeeding female subject or male subject whose partner is pregnant or planning on becoming pregnant. Subject with any of the following laboratory abnormalities: Platelet count <90,000/mm3; Absolute neutrophil count <1500 cells/mm3; Hemoglobin <12 g/dL for women and <13 g/dL for men; Creatinine >1.5 mg/dL; Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN); Total serum bilirubin >1.5 x ULN; Subjects without cirrhosis and AFP >50 ng/mL must have an ultrasound between the screening and baseline visit with no findings suspicious for HCC. Medical conditions which are contraindications for PegIFNα 2a or RBV therapy: Psychiatric disorders; Organ transplant (other than cornea or hair transplant or skin graft); Severe concurrent medical disease such as severe hypertension, significant coronary heart disease, poorly controlled diabetes mellitus (glycated hemoglobin A1c [HbA1c] >8.5%), not adequately controlled thyroid dysfunction, chronic obstructive pulmonary disease, severe infections (bacterial, viral, fungal, including acute tuberculosis), or hemoglobinopathies (thalassemia major or sickle cell anemia); Autoimmune hepatitis or other autoimmune conditions known to be exacerbated by PegIFNα 2a and RBV. History of a severe seizure disorder or current anticonvulsant use. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (e.g., due to diabetes mellitus or hypertension). Other cases judged by the investigator to be ineligible for participation in the study.

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 (low dose)<br>an add-on drug (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: Pegasys;Drug: Ribavirin<br>* conventional treatment of Hepatitis C<br>* Other names: Rebetol;Drug: TCM-700C<br>* An add-on drug to conventional treatment of Hepatitis C<br>|
| Experimental: TCM-700C (high dose)<br>an add-on drug (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: Pegasys;Drug: Ribavirin<br>* conventional treatment of Hepatitis C<br>* Other names: Rebetol;Drug: TCM-700C<br>* An add-on drug to conventional treatment of Hepatitis C<br>|
| Placebo Comparator: Placebo<br>placebo add on(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: Pegasys;Drug: Ribavirin<br>* conventional treatment of Hepatitis C<br>* Other names: Rebetol;Drug: Placebo<br>* Placebo, without acting ingredient.<br>* Other names: Placebo, without acting ingredient.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sustained virologic response (SVR) rate | undetectable HCV RNA 24 weeks after the EOT. | 24 weeks after the end of treatment (EOT, 48 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic response (VR) | undetectable HCV RNA at the EOT. | at the EOT (48 weeks) | 
| relapse rate | undetectable HCV RNA at the EOT followed by a positive HCV RNA level within 24 weeks after the EOT | 24 weeks after the EOT | 

 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