Chronic Hepatitis C Infection
Conditions
Keywords
Hepatitis C Virus, HCV, Herbal treatment, Herbs, San Diego, Non responder, Relapser, Treatment failure, Antifibrotic, Anti-fibrotic, Fibrosis, Failure of previous Interferon based therapy, Refuse Interferon based therapy, Intolerance to Interferon, Male or female 18-70 years of age
Brief summary
Current treatment of chronic liver disease relies upon removing the primary insult to the liver (e.g., alcohol) or treating the underlying viral infection (HBV, HCV, etc.). However, in the case of hepatitis C, a significant number of individuals will not clear the virus with current approved standard antiviral therapy, leaving them no options to manage their hepatic fibrosis, which can progress to cirrhosis and ultimately hepatocellular carcinoma (HCC). Fuzheng Huayu has been used in numerous studies in China and has been found to have a satisfactory prophylaxis effect on the chronic liver injury and formed liver fibrosis in rats and humans. In addition, it enhances the degradation of liver fibrosis and protects hepatocytes from injury and death, manifesting as decreasing of ALT and AST, and enhancement of albumin level. In addition, preliminary studies indicate that the Fuzheng Huayu has a good safety and tolerability profile with promising efficacy. The number of patients failing Interferon based therapy (i.e. not achieving SVR) is increasing. There are no approved standard of care treatment options for this population nor for patients who are intolerant or unwilling to receive Interferon; thus they are at higher risk for the progression of fibrosis. Moreover, there are no approved therapies to treat hepatic fibrosis, but basic research is exploring the pathophysiological mechanisms. Fuzheng Huayu is easy to administer, with a good safety and efficacy profile against fibrosis. Therefore, the investigators propose to further study the safety and efficacy profile of Fuzheng Huayu in a randomized, placebo-controlled, double blind study in Chronic Hepatitis C patients with hepatic fibrosis who have failed prior anti-HCV therapy or are intolerant or refuse Interferon based therapy. The primary objective of this study is to establish the safety and efficacy of Fuzheng Huayu treatment in chronic hepatitis C subjects who have failed prior anti-HCV therapy or cannot receive or refused Interferon based therapy in improving liver fibrosis.
Interventions
DRUGFuzheng Huayu
The subjects will be taking 2 tablets three times a day for 48 weeks.
DRUGPlacebo
The subjects will be taking 2 tablets three times a day for 48 weeks.
Sponsors
Shanghai Sundise Traditional Chinese Medicine Co., Ltd.
Tarek Hassanein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Male or female 18-70 years of age. 2. Chronic hepatitis C infection based on documented history of a positive serum anti-HCV antibody test and/or detectable levels of HCV RNA ≥ 50 IU/mL. 3. Failure to achieve sustained Virologic response (SVR) with previous Interferon based therapy or subjects who refuse Interferon based therapy or are intolerant to Interferon. 4. All subjects enrolling in the study and all fertile or potentially fertile sexual partners of subjects must be using two reliable forms of effective contraception during the study unless a study participant/partner is surgically sterile or postmenopausal. Main
Exclusion criteria
1. Subjects with any history of decompensated liver disease, including but not restricted to portal hypertension as manifested by gastroesophageal varices, variceal bleeding, ascites, or encephalopathy or a hepatic mass lesion suspicious for hepatocellular carcinoma (HCC). 2. Liver histology consistent with any other co-existing cause of chronic liver disease (apart from fatty liver). 3. Subjects who have been treated for HCV infection within 6 months before Screening. 4. Subjects who have been on any experimental protocol or therapy within 28 days before Screening. 5. Known HIV infection. 6. Chronic hepatitis B infection 7. Uncontrolled diabetes. 8. Unstable or uncontrolled thyroid disease 9. Uncontrolled seizures disorder. 10. History of malignant cancer within the last 5 years with the exception of localized basal or squamous cell carcinoma. 11. Alcohol and/or drug abuse within the past year. 12. Pregnant or lactating women or women who plan to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Baseline to Week 60 | Safety will be evaluated through the changes in vital signs, physical examinations, adverse events, concomitant medication assessments as well as laboratory tests. |
| Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Baseline to Week 48 | Efficacy of Fuzheng Huayu treatment was assessed through the change in liver fibrosis stage from the assessment before (pre) and after (post) study drug. The liver fibrosis staging system used was the Ishak scale. The Ishak liver fibrosis score ranges from 0 indicating no fibrosis to 6 indicating cirrhosis. Fibrosis improved was defined as a lower post study drug Ishak score, by at least 1 point, from pre-study drug assessment of the liver fibrosis e.g. if a pre study drug Ishak score of 4 and then a post study drug Ishak score of 3 or lower. Fibrosis did not change was defined as having the same Ishak score before and after study drug assessments e.g. if a pre study drug Ishak score of 4 and then a post study drug Ishak score of 4. Fibrosis worsened was defined as a higher post study drug Ishak score, by at least 1 point, from pre-study drug assessment of the liver fibrosis e.g. if a pre study drug Ishak score of 4 and then a post study drug Ishak score of 5 or higher. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fuzheng Huayu Pill with Fuzheng Huayu
Fuzheng Huayu: The subjects will be taking 2 tablets three times a day for 48 weeks. | 59 |
| Placebo Pill without Fuzheng Huayu (sugar pill)
Placebo: The subjects will be taking 2 tablets three times a day for 48 weeks. | 59 |
| Total | 118 |
Baseline characteristics
| Characteristic | Fuzheng Huayu | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 6.72 | 55.1 years STANDARD_DEVIATION 8.61 | 55.3 years STANDARD_DEVIATION 7.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 50 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotypes 1 | 48 participants | 52 participants | 100 participants |
| HCV Genotypes 2 | 4 participants | 1 participants | 5 participants |
| HCV Genotypes 3 | 6 participants | 5 participants | 11 participants |
| HCV Genotypes 4 | 1 participants | 0 participants | 1 participants |
| HCV Genotypes Other | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 25 Participants | 23 Participants | 48 Participants |
| Sex: Female, Male Male | 34 Participants | 36 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 59 | 55 / 59 |
| serious Total, serious adverse events | 7 / 59 | 10 / 59 |
Outcome results
Primary
Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy.
Efficacy of Fuzheng Huayu treatment was assessed through the change in liver fibrosis stage from the assessment before (pre) and after (post) study drug. The liver fibrosis staging system used was the Ishak scale. The Ishak liver fibrosis score ranges from 0 indicating no fibrosis to 6 indicating cirrhosis. Fibrosis improved was defined as a lower post study drug Ishak score, by at least 1 point, from pre-study drug assessment of the liver fibrosis e.g. if a pre study drug Ishak score of 4 and then a post study drug Ishak score of 3 or lower. Fibrosis did not change was defined as having the same Ishak score before and after study drug assessments e.g. if a pre study drug Ishak score of 4 and then a post study drug Ishak score of 4. Fibrosis worsened was defined as a higher post study drug Ishak score, by at least 1 point, from pre-study drug assessment of the liver fibrosis e.g. if a pre study drug Ishak score of 4 and then a post study drug Ishak score of 5 or higher.
Time frame: Baseline to Week 48
Population: Participants who at least took one dose of study drug (Fuzheng Huayu or Placebo), were more than 80% compliant with study drug and had a pre and post study drug biopsy with an evaluable Ishak fibrosis score. Participants had ALT \<300 and a BMI \<40.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fuzheng Huayu | Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Fibrosis improved | 9 participants |
| Fuzheng Huayu | Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Fibrosis did not change | 18 participants |
| Fuzheng Huayu | Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Fibrosis worsened | 11 participants |
| Placebo | Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Fibrosis improved | 13 participants |
| Placebo | Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Fibrosis did not change | 12 participants |
| Placebo | Efficacy of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Fibrosis worsened | 18 participants |
Primary
Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy.
Safety will be evaluated through the changes in vital signs, physical examinations, adverse events, concomitant medication assessments as well as laboratory tests.
Time frame: Baseline to Week 60
Population: Number of participants randomized and who received at least one dose of Fuzheng Huayu or Placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one serious adverse event | 7 Participants |
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who had worsening of white blood cell count from baseline to week 48 | 42 Participants |
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one adverse event related to study drug | 42 Participants |
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who had worsening of Platelets count from baseline to week 48 | 42 Participants |
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one serious adverse event related to study drug | 0 Participants |
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who had worsening of liver enzymes from baseline to week 48 | 43 Participants |
| Fuzheng Huayu | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one adverse event | 55 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who had worsening of liver enzymes from baseline to week 48 | 45 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one adverse event | 55 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one adverse event related to study drug | 38 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one serious adverse event | 10 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who experienced at least one serious adverse event related to study drug | 1 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who had worsening of white blood cell count from baseline to week 48 | 45 Participants |
| Placebo | Safety of Fuzheng Huayu Treatment in Chronic Hepatitis C Subjects Who Have Failed Prior Anti-HCV Therapy or Cannot Receive or Refused Interferon Based Therapy. | Number of participants who had worsening of Platelets count from baseline to week 48 | 45 Participants |