Peripheral Blood Mononuclear Cell (PBMC) Gene Expression in HCV Genotype 1 Patients

NCT00680173 | Completed Phase 4 DMC

• 1 other identifier: KMUH-IRB- 950419
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Our previous collaborative studies has developed a molecular diagnosis tool, which is characterized with a prediction model consisting single nucleotide polymorphisms (SNPs), for assessing the efficacy of interferon combined therapy for chronic hepatitis C (CHC) patients prior to treatment. Aims of this project:

1. 1.To analyze and validate the gene expression profiling dependent of treatment response to peg-interferon-α plus ribavirin combination therapy in CHC genotype-1 patients.
2. 2.To select the candidate genes and establish a monitoring model assessing the efficacy of interferon treatment.

Conditions

Chronic Hepatitis C

Keywords

Chronic Hepatitis C; Single nucleotide polymorphisms; Sustained virological response; Peginterferon; Ribavirin

Outcome Measures

Primary Outcomes (1)

• Efficacy - Sustained virological response (SVR), HCV RNA seronegative by PCR throughout 24-week off-treatment period.

  1.5 year

Secondary Outcomes (3)

• Rapid virologic response (RVR), HCV RNA seronegative by PCR at week 4.

  1.5 year

• Early virological response (EVR), by PCR-negative or at least 2 logs decline from baseline of serum HCV RNA at 12 weeks of treatment.

  1.5 year

• Safety - adverse event rate and profile

  1.5 year

Study Arms (2)

A

ACTIVE COMPARATOR

15 patients with HCV genotype 1 infection receiving peginterferon plus ribavirin achieve a sustained virological response

Drug: pegylated interferon alpha 2a and plus ribavirin

B

ACTIVE COMPARATOR

15 patients with HCV genotype 1 infection receiving peginterferon plus ribavirin did not achieve a sustained virological response

Drug: pegylated interferon alpha 2a and plus ribavirin

Interventions

pegylated interferon alpha 2a and plus ribavirin DRUG

pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 24 weeks, follow up for 24 weeks

Also known as: PEGASYS®

A; B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients \>18 years of age
• Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin
• Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
• Detectable serum HCV-RNA
• Liver biopsy findings consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis (Exception: hemophiliacs in whom biopsy is medically contra-indicated do not require biopsy.)
• Compensated liver disease (Child-Pugh Grade A clinical classification)
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
• All fertile males and females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end

You may not qualify if:

• Women with ongoing pregnancy or breast feeding
• Present therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug
• Any investigational drug 6 weeks prior to the first dose of study drug
• Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV)
• History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
• Clinical evidence of hepatocellular carcinoma
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• Neutrophil count \<1500 cells/mm3 or platelet count \<90,000 cells/mm3 at screening
• Serum creatinine level \>1.5 times the upper limit of normal at screening
• History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
• History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
• Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
• Evidence of drug abuse (including excessive alcohol consumption\>40 g/day) within one year of study entry

Sponsors & Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital: lead

Study Sites (1)

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Related Publications (4)

• Dai CY, Chuang WL, Hsieh MY, Lee LP, Hou NJ, Chen SC, Lin ZY, Hsieh MY, Wang LY, Tsai JF, Chang WY, Yu ML. Polymorphism of interferon-gamma gene at position +874 and clinical characteristics of chronic hepatitis C. Transl Res. 2006 Sep;148(3):128-33. doi: 10.1016/j.trsl.2006.04.005.

  PMID: 16938650 BACKGROUND

• Houldsworth A, Metzner M, Rossol S, Shaw S, Kaminski E, Demaine AG, Cramp ME. Polymorphisms in the IL-12B gene and outcome of HCV infection. J Interferon Cytokine Res. 2005 May;25(5):271-6. doi: 10.1089/jir.2005.25.271.

  PMID: 15871664 BACKGROUND

• Naito M, Matsui A, Inao M, Nagoshi S, Nagano M, Ito N, Egashira T, Hashimoto M, Mishiro S, Mochida S, Fujiwara K. SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C. J Gastroenterol. 2005 Apr;40(4):381-8. doi: 10.1007/s00535-005-1558-3.

  PMID: 15868370 BACKGROUND

• Suzuki F, Arase Y, Suzuki Y, Tsubota A, Akuta N, Hosaka T, Someya T, Kobayashi M, Saitoh S, Ikeda K, Kobayashi M, Matsuda M, Takagi K, Satoh J, Kumada H. Single nucleotide polymorphism of the MxA gene promoter influences the response to interferon monotherapy in patients with hepatitis C viral infection. J Viral Hepat. 2004 May;11(3):271-6. doi: 10.1111/j.1365-2893.2004.00509.x.

  PMID: 15117331 BACKGROUND

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wan-Long Chuang, MD, PhD

  Kaohsiung Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., PhD.

Study Record Dates

• First Submitted: May 15, 2008
• First Posted: May 19, 2008
• Study Start: August 1, 2006
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: March 14, 2016

Record last verified: 2016-03

Locations

TW (1)