36 vs 48 Wks Peg-Intron Plus Ribavirin for HCV Patients Without Rapid Virologic Response But Without HCV RNA at wk 8

An Open Label, Randomized, Parallel Design Estimation Pilot Study to Compare the Effectiveness of 36 vs 48 Wks PegIntron Plus Ribavirin Treatment for HCV Patients Without Rapid Virologic Response(RVR) But With Undetectable HCV RNA at wk 8

Purpose:

To compare the effectiveness of 36 weeks versus 48 weeks pegintron plus ribavirin treatment for hepatitis C virus(HCV) patients without rapid virologic response(RVR), but with undetectable HCV RNA at wk 8.

Study Design:

a multi-site, prospective, open label, randomized, pilot trial. Approximately 60 HCV Genotype 1 patients who fail to achieve RVR but achieve undetectable HCV RNA at week 8 (<50 IU/ml) will be recruited into 2 arms(30 in each arm). Patients must receive pegylated interferon-α2b at 1.5 μg/kg of body weight/week and ribavirin 800~1400 mg/day for 12 wks before entering this study.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Pegintron + Riba

Detailed Description

Purpose:

To compare the effectiveness of 36 wks versus 48 wks pegintron plus ribavirin treatment for HCV patients without RVR, but with undetectable HCV RNA at wk 8.

Study Design:

This is a multi-site, prospective, open label, randomized, pilot trial. Approximately 60 HCV Genotype 1 patients who fail to achieve RVR at wk 4 but achieve undetectable HCV RNA at wk 8 (<50 IU/ml) will be recruited into 2 arms(30 in each arm). Patients must receive pegylated IFN-α2b at 1.5 μg/kg of body weight/week and ribavirin 800~1400 mg/day for 12 wks before entering this study.

Study Duration:

The estimated recruitment period is 12 months; the follow-up duration is 72 weeks (longest treatment period plus 6 month- f/u period); the total study duration (FPE->LPLV) is estimated to be 2.5 years

Statistical Analysis and Sample Size Justification:

A. The study is not primarily designed for hypothesis testing; thus the sample size calculation is not based on the primary objective, Approximately 60 subjects (30 in each arm) will be recruited into this study B. For descriptive statistics, the continuous variables will be expressed as mean ± standard deviation, and the categorical variables will be performed the number of cases and the corresponding percentages.

The primary analysis will focus on the efficacy response to the shortened HCV treatment course (36 wks) compared with standard course (48 wks). The between-group difference for efficacy endpoint will be assessed by the difference in the percentage of virologic responder after 24 wks of HCV treatment. For univariate analyses, comparisons of independent samples (shortened vs. standard course) will be assessed with Student's t test. The comparisons of categorical variables will be assessed using the chi-square test. Regarding the multivariate analysis, the proportion of patients achieving virologic responder will be compared among groups using a logistic regression analysis with terms of potential confounding factors. The OR estimates will be derived from the logistic regression model and the corresponding 95% CIs will be used to quantify the each effect of treatment course length and confounding factors.

All randomized patients who take at least one dose of HCV regimen will be included in safety assessment. Fisher's exact test will be used to compare between-group incidences of AEs. For patients with any clinical AEs, treatment related AEs, serious AEs, or discontinuations because of AEs, the data among groups will be provided as well. Statistical significance will be determined at the 0.05 level for all tests.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 81362
    • Recruiting
    • Kaohsiung Veterans General Hospital
    • Contact: Hsien-Chung Yu, M.D.; Phone Number: 2074 886-7-3422121; Email: hcyu@vghks.gov.tw
    • Principal Investigator: Tsung-Hui Hu, M.D.
  • Kaohsiung, Taiwan
    • Recruiting
    • Chang Gung Medical Foundation, Kaohsiung Branch
    • Contact: Tsung-Hui Hu, M.D.; Phone Number: 8301 886-7-7317123; Email: Dr.hu@msa.hinet.net
    • Principal Investigator: Tsung-Hui Hu, M.D.
  • Pingtung, Taiwan, 900
    • Recruiting
    • Pingtung Christian Hospital
    • Contact: Lian-Feng Lin, M.D.; Phone Number: 2032 886-8-7368686; Email: lin.lian.feng@gmail.com
    • Principal Investigator: Lian-Feng Lin, M.D.
  • Tainan, Taiwan, 736
    • Recruiting
    • Chi Mei Medical Center - Liouying Branch
    • Contact: Jyh-Jou Chen, M.D.; Phone Number: 72008 886-6-6226999; Email: jjchen@mail.chimei.org.tw
    • Principal Investigator: Jyh-Jou Chen, M.D.
  • Taipei, Taiwan, 111
    • Recruiting
    • Shin Kong Wu Ho-Su Memorial Hosipital
    • Contact: Chao-Sheng Liao, M.D.; Phone Number: 2031 886-2-28332211; Email: M000642@ms.skh.org.tw
    • Principal Investigator: Chao-Sheng Liao, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 20y/o or older
2. Positive for the HCV antibody and HCV RNA detected with abnormal ALT (≧ 1X) before initiating PegIFN plus RBV treatment
3. HCV Genotype 1
4. Have failed to achieve RVR at week 4 but achieve undetectable HCV RNA at week 8 (< 50 IU/ml) with PegIFN plus RBV treatment
5. Have received PegIFN plus RBV treatment for 12weeks with good compliance (who have received >80% of expected PegIFN and RBV doses and completed at least 80% of the expected duration (80/80/80 adherence) and achieve EVR before entering this study

Exclusion Criteria:

1. Subjects with decompensated liver disease or overt cirrhosis by ultrasound.
2. With prior exposures to interferon (standard or pegylated) treatment before baseline.
3. With human immunodeficiency virus
4. With hepatitis B infection
5. With neutrophil count < 1500 mm3,
6. With platelet count < 90000 mm3,
7. With hemoglobin level < 12g/dL for men or < 11 g/dL for women
8. With serum creatinine level > 1.5 mg/dL
9. With clinically significant cardiac or cardiovascular abnormalities, organ grafts, systemic infections, clinically significant bleeding disorders, evidence of malignant neoplastic diseases
10. Female patients with pregnancy or lactation. Pregnancy in partners of male patients.
11. Hypersensitive to study drugs cases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegintron + Riba for 36 wks in total; Pegylated IFN-α2b at 1.5 µg/kg of body weight/week and ribavirin 800~1400 mg/day for 24 weeks (36 weeks in total HCV treatment)	Drug: Pegintron + Riba; Pegylated IFN-α2b at 1.5 µg/kg of body weight/week and ribavirin 800~1400 mg/day
Active Comparator: Pegintron + Riba for 48 wks in total; Pegylated IFN-α2b at 1.5 µg/kg of body weight/week and ribavirin 800~1400 mg/day for 36 weeks (48 weeks in total HCV treatment)	Drug: Pegintron + Riba; Pegylated IFN-α2b at 1.5 µg/kg of body weight/week and ribavirin 800~1400 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of sustained virologic response	The comparison of the rates of sustained virologic response (SVR) defined as the proportion of patients with loss of serum HCV RNA at week 24 of post-treatment between patient groups (36 vs 48 weeks of treatment period)	At 24 weeks after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the factors associated with sustained virologic response(SVR) between groups	the SVR assessment is defined as 24 weeks after the end of treatment, which mean 48 weeks after randomization for the shorten treatment arm and 60 weeks after randomization for the standard treatment arm	24 weeks after the end of treatment
the rate of end-of-treatment response(EOT)	The comparison of the rates of end-of-treatment response (EOT) defined as the proportion of patients with loss of serum HCV RNA at the end of treatment between patient groups (36 vs 48 weeks of treatment period)	At the end of treatment (36 or 48 weeks of treatment period)
The relapse rate	The comparison of the relapse rates defined as the proportion of patients without detectable serum HCV RNA at the end of treatment but with detectable HCV RNA at 24 weeks after end of treatment between patient groups (36 vs 48 weeks of treatment period)	At 24 weeks after end of treatment

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Tsung-Hui Hu, M.D., Chang Gung Medical Foundation, Kaohsiung Branch

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimate): September 12, 2012

Study Record Updates

• Last Update Posted (Estimate): September 12, 2012
• Last Update Submitted That Met QC Criteria: September 11, 2012
• Last Verified: September 1, 2012

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; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2b
• Other Study ID Numbers: MISP39068