Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis C Infection - Full Text View

Purpose

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)

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: KRN7000	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Single Group Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis C Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

U.S. FDA Resources

Further study details as provided by Foundation for Liver Research:

Primary Outcome Measures:

Decrease in serum hepatitis C virus ribonucleic acid (HCV RNA) levels.

Secondary Outcome Measures:

Normalization of serum ALT levels.
Effect on serum cytokines IFNg and TNFa and on iNKT cells.


Estimated Enrollment:	36
Study Start Date:	August 2003
Estimated Study Completion Date:	May 2005

Detailed 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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352235

Locations


Netherlands
Erasmus MC
Rotterdam, Netherlands, 3000CA

Sponsors and Collaborators

Foundation for Liver Research

Kyowa Hakko Kirin Co., Ltd

Investigators


Principal Investigator:	Carin MJ van Nieuwkerk, MD, PhD	VU medical Center, Amsterdam

More Information


ClinicalTrials.gov Identifier:	NCT00352235 History of Changes
Other Study ID Numbers:	KRN7000 HCV
Study First Received:	July 13, 2006
Last Updated:	July 13, 2006

Keywords provided by Foundation for Liver Research:


Chronic hepatitis C KRN7000 a-GalCer	immunotherapy Natural Killer T cells interferon

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases	Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections KRN 7000 Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents

ClinicalTrials.gov processed this record on May 25, 2017