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

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

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

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: KRN7000


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: KRN7000|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in serum hepatitis C virus ribonucleic acid (HCV RNA) levels. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalization of serum ALT levels. |  |  | 
| Effect on serum cytokines IFNg and TNFa and on iNKT cells. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hepatitis C, KRN7000, a-GalCer, immunotherapy, Natural Killer T cells, interferon