Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis C Infection

Chronic Hepatitis C Clinical Trial

Official title:

Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00352235
• Other study ID #: KRN7000 HCV
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 13, 2006
• Last updated: July 13, 2006
• Start date: August 2003
• Est. completion date: May 2005

Study information

• Verified date: July 2006
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Phase I/II trial of KRN7000 in patients with chronic hepatitis C.

Study objectives: To evaluate and compare the safety and tolerability of 3 ascending doses of a-GalCer.

The primary efficacy parameter: HCV-RNA response at the end of treatment. Secondary efficacy parameter: Serum ALT response. Further objectives of the study are to evaluate the effect of a-GalCer on serum cytokines IFNg and TNFa and on iNKT cells.

Number of dose levels: 3 Investigational product: KRN7000 Route of administration:

intravenous Dosages and frequency: 0.1, 1, 10 mcg/kg, monthly injection, 3 times (day 0, day 28 and day 56)

Description:

Phase I/II trial of KRN7000 in patients with chronic hepatitis C.

This study is a multicenter double-blind randomized placebo-controlled phase I/II dose-escalation trial. The protocol is conducted in The Netherlands, Belgium and Germany. Patients with chronic hepatitis C who met the inclusion criteria are assigned to receive a-GalCer (KRN7000 ((2S, 3S, 4R)-1-O-(a-D-galactopyranosyl)-N-hexacosanoyl-2-amino-1,3,4-octadecanetriol), Kirin Pharmaceutical Co., Ltd., Gunma, Japan) or placebo intravenously, thrice with intervals of 4 weeks. Cohorts of 12 patients are entered at each of the three dose levels (0.1, 1 and 10 mg/kg body weight). Three patients per dose level are randomized to the placebo arm.

Dose escalation to the next cohort are decided after evaluation by a safety review board of all the safety data collected on all the patients who had completed 3 weeks after the first injection in the preceding dose cohort. After completion of 8 weeks of treatment, with injections at 0, 4 and 8 weeks, patients are monitored without further therapy for an additional 16 weeks.

Study objectives: The objective of the study is to evaluate and compare the safety and tolerability of 3 ascending doses of a-GalCer. The primary efficacy parameter is the response at the end of treatment, based on serum hepatitis C virus ribonucleic acid (HCV RNA) levels. As a secondary efficacy parameter serum ALT levels are evaluated. Further objectives of the study are to evaluate the effect of a-GalCer on serum cytokines IFNg and TNFa and on iNKT cells.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Chronic hepatitis C Liver biopsy within 3 years of entry into the study HCV RNA > 10000 copies/mL Age 18-70 years ALT > 1.2 times ULN written informed consent Adequate contraception

Exclusion Criteria:

Cirrhosis Decompensated liver disease ALT > 10 times ULN Pregnancy Major other illness

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• KRN7000

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Foundation for Liver Research	Kyowa Hakko Kirin Company, Limited

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decrease in serum hepatitis C virus ribonucleic acid (HCV RNA) levels.
Secondary	Normalization of serum ALT levels.
Secondary	Effect on serum cytokines IFNg and TNFa and on iNKT cells.