Assess the Antifibrotic Activity of Fuzheng Huayu in Chronic Hepatitis C Patients With Hepatic Fibrosis

• Sponsor: Tarek Hassanein (Other)
• Overall Status: Completed
• CT.gov ID: NCT00854087
• Collaborator: Shanghai Sundise Traditional Chinese Medicine Co., Ltd. (Industry)
• Enrollment: 118
• Locations: 8
• Arms: 2
• Duration (Months): 36
• Patients Per Site: 14.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: Fuzheng Huayu; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study to Assess the Antifibrotic Activity of Fuzheng Huayu in Chronic Hepatitis C Patients With Hepatic Fibrosis
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fuzheng Huayu Pill with Fuzheng Huayu	Drug: Fuzheng Huayu; The subjects will be taking 2 tablets three times a day for 48 weeks.; Other Names: Gan Ping 319 Recipe FZHY
Placebo Comparator: Placebo Pill without Fuzheng Huayu (sugar pill)	Drug: Placebo; The subjects will be taking 2 tablets three times a day for 48 weeks.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SCTI Research Foundation	Coronado	California	United States	92118
2	VA Palo Alto HCS	Palo Alto	California	United States	94304
3	Huntington Medical Research Institutes	Pasadena	California	United States	91105
4	UC Davis Health System	Sacramento	California	United States	95817
5	Southern California Liver Centers	San Clemente	California	United States	92673
6	Advanced Medical Research Center	Port Orange	Florida	United States	32127
7	St. Luke's Advanced Liver Therapies	Houston	Texas	United States	77030
8	University of Utah HSC	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

• Tarek Hassanein
• Shanghai Sundise Traditional Chinese Medicine Co., Ltd.

Investigators

• Principal Investigator: Tarek Hassanein, MD, SCTI Research Foundation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tarek Hassanein, Medical Director, SCTI Research Foundation
• ClinicalTrials.gov Identifier: NCT00854087
• Other Study ID Numbers: Fuzheng Huayu S-USIIT-01 Study
• First Posted: Mar 2, 2009
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Tarek Hassanein, Medical Director, SCTI Research Foundation: 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
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Fibrosis

Study Results

Participant Flow

Arm/Group Title	Fuzheng Huayu	Placebo
Arm/Group Description	Pill with Fuzheng Huayu Fuzheng Huayu: The subjects will be taking 2 tablets three times a day for 48 weeks.	Pill without Fuzheng Huayu (sugar pill) Placebo: The subjects will be taking 2 tablets three times a day for 48 weeks.
Period Title: Overall Study
STARTED	59	59
COMPLETED	40	40
NOT COMPLETED	19	19

Baseline Characteristics

Arm/Group Title	Fuzheng Huayu	Placebo	Total
Arm/Group Description	Pill with Fuzheng Huayu Fuzheng Huayu: The subjects will be taking 2 tablets three times a day for 48 weeks.	Pill without Fuzheng Huayu (sugar pill) Placebo: The subjects will be taking 2 tablets three times a day for 48 weeks.	Total of all reporting groups
Overall Participants	59	59	118
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.4 (6.72)	55.1 (8.61)	55.3 (7.67)
Sex: Female, Male (Count of Participants)
Female	25 42.4%	23 39%	48 40.7%
Male	34 57.6%	36 61%	70 59.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 8.5%	9 15.3%	14 11.9%
Not Hispanic or Latino	54 91.5%	50 84.7%	104 88.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
HCV Genotypes (participants) [Number]
1	48 81.4%	52 88.1%	100 84.7%
2	4 6.8%	1 1.7%	5 4.2%
3	6 10.2%	5 8.5%	11 9.3%
4	1 1.7%	0 0%	1 0.8%
Other	0 0%	1 1.7%	1 0.8%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants randomized and who received at least one dose of Fuzheng Huayu or Placebo.

Arm/Group Title	Fuzheng Huayu	Placebo
Arm/Group Description	Pill with Fuzheng Huayu Fuzheng Huayu: The subjects will be taking 2 tablets three times a day for 48 weeks.	Pill without Fuzheng Huayu (sugar pill) Placebo: The subjects will be taking 2 tablets three times a day for 48 weeks.
Measure Participants	59	59
Number of participants who experienced at least one adverse event	55 93.2%	55 93.2%
Number of participants who experienced at least one adverse event related to study drug	42 71.2%	38 64.4%
Number of participants who experienced at least one serious adverse event	7 11.9%	10 16.9%
Number of participants who experienced at least one serious adverse event related to study drug	0 0%	1 1.7%
Number of participants who had worsening of white blood cell count from baseline to week 48	42 71.2%	45 76.3%
Number of participants who had worsening of Platelets count from baseline to week 48	42 71.2%	45 76.3%
Number of participants who had worsening of liver enzymes from baseline to week 48	43 72.9%	45 76.3%

2. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Fuzheng Huayu	Placebo
Arm/Group Description	Pill with Fuzheng Huayu Fuzheng Huayu: The subjects will be taking 2 tablets three times a day for 48 weeks.	Pill without Fuzheng Huayu (sugar pill) Placebo: The subjects will be taking 2 tablets three times a day for 48 weeks.
Measure Participants	38	43
Fibrosis improved	9 15.3%	13 22%
Fibrosis did not change	18 30.5%	12 20.3%
Fibrosis worsened	11 18.6%	18 30.5%

Adverse Events

Time Frame	Study duration (screening through last study visit)
Arm/Group Title	Fuzheng Huayu		Placebo
Arm/Group Description	Pill with Fuzheng Huayu Fuzheng Huayu: The subjects will be taking 2 tablets three times a day for 48 weeks.		Pill without Fuzheng Huayu (sugar pill) Placebo: The subjects will be taking 2 tablets three times a day for 48 weeks.
All Cause Mortality
	Fuzheng Huayu		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fuzheng Huayu		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/59 (11.9%)		10/59 (16.9%)
Gastrointestinal disorders
Bowel Obstruction	1/59 (1.7%)	1	1/59 (1.7%)	1
Abdominal Pain	1/59 (1.7%)	1	1/59 (1.7%)	1
General disorders
Atypical Chest Pain	1/59 (1.7%)	1	0/59 (0%)	0
Hepatobiliary disorders
Cholecystitis	2/59 (3.4%)	2	0/59 (0%)	0
Infections and infestations
Acute Hepatitis	0/59 (0%)	0	1/59 (1.7%)	1
Injury, poisoning and procedural complications
T-12 Compression	0/59 (0%)	0	1/59 (1.7%)	1
Opiod Overdose	1/59 (1.7%)	1	0/59 (0%)	0
Metabolism and nutrition disorders
Hypokalemia/Hyponatremia/Nausea/Vomiting	0/59 (0%)	0	1/59 (1.7%)	1
Musculoskeletal and connective tissue disorders
Transverse Myelilitis	0/59 (0%)	0	1/59 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleomorphic Rhabdomyosarcoma	1/59 (1.7%)	1	0/59 (0%)	0
Ovarian Adenoma	0/59 (0%)	0	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Sinus Infection	0/59 (0%)	0	1/59 (1.7%)	1
Pneumonia	0/59 (0%)	0	2/59 (3.4%)	2
Social circumstances
Alcohol Rehabilitation	0/59 (0%)	0	1/59 (1.7%)	1
Vascular disorders
Hypotension	0/59 (0%)	0	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Fuzheng Huayu		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/59 (93.2%)		55/59 (93.2%)
Cardiac disorders
Cardiac disorders such as tachycardia	2/59 (3.4%)	2	4/59 (6.8%)	4
Ear and labyrinth disorders
Ear disorders such as vertigo	3/59 (5.1%)	3	1/59 (1.7%)	1
Endocrine disorders
Endocrine disorders (hypothyroidism)	0/59 (0%)	0	1/59 (1.7%)	1
Eye disorders
Eye disorders such as dry eye	3/59 (5.1%)	3	3/59 (5.1%)	3
Gastrointestinal disorders
Gastrointestinal disorders such as nausea	39/59 (66.1%)	84	30/59 (50.8%)	75
General disorders
General disorders such as fatigue	27/59 (45.8%)	44	21/59 (35.6%)	27
Hepatobiliary disorders
Hepatobiliary disorders (acute cholecistitis)	1/59 (1.7%)	1	0/59 (0%)	0
Immune system disorders
Immune system disorders such as rhinitis allergy	3/59 (5.1%)	3	3/59 (5.1%)	3
Infections and infestations
Infections such as urinary tract infection	24/59 (40.7%)	26	20/59 (33.9%)	34
Injury, poisoning and procedural complications
Injury, posioning and procedural complications such as muscle strain	10/59 (16.9%)	11	12/59 (20.3%)	14
Investigations
Investigations such as liver biopsy	6/59 (10.2%)	6	8/59 (13.6%)	8
Metabolism and nutrition disorders
Metabolism and nutrition disorders such as decreased appetite	5/59 (8.5%)	8	5/59 (8.5%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms such as ovarian cysts	3/59 (5.1%)	3	1/59 (1.7%)	1
Nervous system disorders
Nervous system disorders such as headache	20/59 (33.9%)	46	21/59 (35.6%)	35
Psychiatric disorders
Psychiatric disorders such as depression	15/59 (25.4%)	20	15/59 (25.4%)	23
Renal and urinary disorders
Renal and urinary disorders such as nocturia	7/59 (11.9%)	8	2/59 (3.4%)	2
Reproductive system and breast disorders
Reproductive system disorders such as erectile dysfunction	1/59 (1.7%)	1	2/59 (3.4%)	3
Respiratory, thoracic and mediastinal disorders
Respiratory such as cough	20/59 (33.9%)	36	24/59 (40.7%)	58
Skin and subcutaneous tissue disorders
Skin and subcutaneous system disorders such as rash	14/59 (23.7%)	17	13/59 (22%)	19
Social circumstances
Social circumstances (alcohol rehabilitation)	0/59 (0%)	0	1/59 (1.7%)	1
Surgical and medical procedures
Surgical and medical procedures such as knee surgery	6/59 (10.2%)	9	8/59 (13.6%)	8
Vascular disorders
Vascular disorders such as hypertension	2/59 (3.4%)	2	5/59 (8.5%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.