Chronic Hepatitis C
Conditions
Keywords
add-on treatment, botanical drug, HCV genotype 1, TCM-700C, genotype I
Brief summary
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
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.
Interventions
DRUGTCM-700C
An add-on drug to conventional treatment of Hepatitis C
DRUGPeginterferon alfa-2a
conventional treatment of Hepatitis C
DRUGRibavirin
conventional treatment of Hepatitis C
DRUGPlacebo
Placebo, without acting ingredient.
Sponsors
TCM Biotech International Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response (SVR) | 24 weeks after the termination of combinational drug treatment (up to 72 weeks) | 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.. 1. 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. 2. 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. 3. 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Response | at the end of combination drug treatment (up to 48 weeks) | 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). |
| ALT Response | at the end of combination drug treatment (up to 48 weeks) | 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) |
| Sustained ALT Response | 24 weeks after the termination of combinational drug treatment (up to 72 weeks) | a sustained ALT response is defined as sustained normalization of ALT 24 weeks after cessation of combination drug treatment. |
| Combined ALT and Virologic Response | at the end of combination drug treatment (up to 48 weeks) | Combined ALT and virologic response at the end of combination drug treatment. |
| Immune Cell Normalization | at the end of combination drug treatment (up to 48 weeks) | 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) |
Countries
Taiwan
Participant flow
Recruitment details
recruitment period: 12 Months location: CGMH clinical ceters
Participants by arm
| Arm | Count |
|---|---|
| TCM-700C TCM-700C, an add-on drug to conventional treatment of Hepatitis C | 42 |
| Placebo Placebo with convetional treatment for HCV patients | 42 |
| Total | 84 |
Baseline characteristics
| Characteristic | TCM-700C | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 42 Participants | 84 Participants |
| Age, Continuous | 48.6 years STANDARD_DEVIATION 9.58 | 48.74 years STANDARD_DEVIATION 11.52 | 48.67 years STANDARD_DEVIATION 10.53 |
| Fibrosis score Fibrosis score 0 | 0 participants | 2 participants | 2 participants |
| Fibrosis score Fibrosis score 1 | 11 participants | 21 participants | 32 participants |
| Fibrosis score Fibrosis score 2 | 31 participants | 19 participants | 50 participants |
| Region of Enrollment Taiwan | 42 participants | 42 participants | 84 participants |
| Sex: Female, Male Female | 22 Participants | 15 Participants | 37 Participants |
| Sex: Female, Male Male | 20 Participants | 27 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 41 | 40 / 42 |
| serious Total, serious adverse events | 9 / 41 | 6 / 42 |
Outcome results
Primary
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.. 1. 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. 2. 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. 3. 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)
Time frame: 24 weeks after the termination of combinational drug treatment (up to 72 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCM-700C | Sustained Virologic Response (SVR) | 27 Number of participants with SVR |
| Placebo | Sustained Virologic Response (SVR) | 29 Number of participants with SVR |
Secondary
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)
Time frame: at the end of combination drug treatment (up to 48 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCM-700C | ALT Response | 32 participants |
| Placebo | ALT Response | 30 participants |
Secondary
Combined ALT and Virologic Response
Combined ALT and virologic response at the end of combination drug treatment.
Time frame: at the end of combination drug treatment (up to 48 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCM-700C | Combined ALT and Virologic Response | 31 participants |
| Placebo | Combined ALT and Virologic Response | 29 participants |
Secondary
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)
Time frame: at the end of combination drug treatment (up to 48 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TCM-700C | Immune Cell Normalization | CD4 | 31 participants |
| TCM-700C | Immune Cell Normalization | NK cells | 37 participants |
| TCM-700C | Immune Cell Normalization | CD8 | 36 participants |
| Placebo | Immune Cell Normalization | CD4 | 27 participants |
| Placebo | Immune Cell Normalization | NK cells | 31 participants |
| Placebo | Immune Cell Normalization | CD8 | 31 participants |
Secondary
Immune Cell Normalization
Normalization of immune cells, CD4, CD8 and NK cells at 24 weeks after cessation of combination drug treatment.
Time frame: 24 weeks after the termination of combinational drug treatment (up to 72 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TCM-700C | Immune Cell Normalization | CD4 | 30 participants |
| TCM-700C | Immune Cell Normalization | CD8 | 34 participants |
| TCM-700C | Immune Cell Normalization | NK cells | 36 participants |
| Placebo | Immune Cell Normalization | CD4 | 25 participants |
| Placebo | Immune Cell Normalization | CD8 | 30 participants |
| Placebo | Immune Cell Normalization | NK cells | 31 participants |
Secondary
Sustained ALT Response
a sustained ALT response is defined as sustained normalization of ALT 24 weeks after cessation of combination drug treatment.
Time frame: 24 weeks after the termination of combinational drug treatment (up to 72 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCM-700C | Sustained ALT Response | 26 participants |
| Placebo | Sustained ALT Response | 27 participants |
Secondary
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).
Time frame: at the end of combination drug treatment (up to 48 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCM-700C | Virologic Response | 34 participants |
| Placebo | Virologic Response | 31 participants |