Clinical Study With Silymarin in the Patients With Chronic Hepatitis C Infection Who Failed Conventional Antiviral Therapy

A Double-blind Phase III Study With Silymarin in the Patients Infected With HCV Who Failed Conventional Antiviral Therapy

The purpose of this study is to determine the effectiveness of silymarin 700 mg thrice daily and assess the safety in patients with hepatitis C virus infection compared to a placebo.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Silymarin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Byung Chul, Yoo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age at least 18 years at screening.
2. Serum HCV RNA above quantifiable level of detection after the end of previous therapy.
3. ALT > 60 IU/L (i.e., approximately 1.5 X upper limit of normal) obtained during the screening period.
4. Previous treatment with any interferon-based therapy but 1) without sustained virological response or 2) HCV RNA detected at the end of the treatment or 3) HCV RNA undetected during the treatment and detected after or 4) have partial response(HCV RNA < 2log10 but is not eradicated) or 5) have no response or 6) discontinuation due to side effect
5. Negative urine pregnancy test (for women of childbearing potential). Females of childbearing potential must be using effective contraception during the study.

Exclusion Criteria:

1. ALT ≥ 10*ULN(Upper Limit of Normal) at the screening
2. Use of silymarin or other milk thistle preparations within 30 days prior to screening.
3. Use of other antioxidants such as vitamin E, vitamin C, glutathione, alpha-tocopherol, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening. A multivitamin at standard doses will be allowed.
4. Use of silymarin or other antioxidants or non-prescribed complementary alternative medications (as above) during the screening period or patient unwilling to refrain from taking these medications through completion of the study.
5. Any antiviral therapy within 6 months prior to screening visit.
6. Known allergy/sensitivity to milk thistle or its preparations.
7. Evidence of poorly-controlled diabetes (defined as HbA1c > 8% in patients with diabetes).
8. Use of warfarin, metronidazole or acetaminophen (greater than two grams per day) within 30 days of screening.
9. Previous Radiology test(Ultrasonography, Computed tomography,Magnetic Resonance Imaging) or liver biopsy that demonstrated presence of moderate to severe steatosis or evidence of steatohepatitis.
10. Positive test for anti-HIV or HBsAg within 5 years of screening.
11. Average alcohol consumption of more than one drink or equivalent (>12 grams) per day or more than two (2) drinks on any one day over the 30 days prior to screening. Patients who met either criterion more than 30 days ago must have consumed a monthly average of 12 grams or less per day of alcohol for at least six months prior to screening.
12. History of other chronic liver disease, including metabolic diseases, documented by appropriate test(s).
13. Women with ongoing pregnancy or breast-feeding, or contemplating pregnancy.
14. Serum creatinine level 2.0 mg/dL or greater at screening or CrCl ≤ 60cc/min, or currently on dialysis. The creatinine clearance (CrCl) will be calculated according to Cockcroft-Gault.
15. Evidence of drug abuse within 6 months prior to screening or during the screening period.
16. Evidence of decompensated liver disease defined as any of the following: serum albumin <3.2 g/dl, total bilirubin > 2.0 mg/dl, or PT/INR > 1.3 times normal at screening, or history or presence of ascites or encephalopathy, or bleeding from esophageal varices.
17. History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, or active gastrointestinal conditions that might interfere with drug absorption).
18. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hepatitis, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect inflammatory biomarkers.
19. History of solid organ or bone marrow transplantation.
20. History of thyroid disease poorly controlled on prescribed medications.
21. Use of oral steroids for more than 14 days within 30 days prior to screening.
22. Participation in a research drug trial within 6 months of enrollment.
23. Inability or unwillingness to provide informed consent or abide by the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: Placebo; Placebo 700mg thrice daily
EXPERIMENTAL: silymarin, treatment	Drug: Silymarin; 700mg thrice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patient with serum ALT less than or equal to 40 IU/L or achieves at least 50% decline to less than 60 IU/L	at week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
the change from baseline in ALT and HCV RNA (log10)	36 weeks

Collaborators and Investigators

• Sponsor: Bukwang Pharmaceutical
• Investigators: Principal Investigator: Byung Chul Yoo, MD. PhD., Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: December 10, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (ESTIMATE): December 13, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 22, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Silymarin
• Other Study ID Numbers: BK SIL-C-301