KRN7000 in Chronic Hepatitis B
The purpose of this trial is to determine the safety, tolerability and effectiveness of KRN7000 for chronic hepatitis B infection.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis B Infection|
- To determine safety and tolerability
- To evaluate effectiveness in reducing HBV DNA load
- To evaluate effectiveness in inducing immunological responses
- TO evaluate effectiveness in normalization of ALT
|Study Start Date:||March 2003|
|Estimated Study Completion Date:||July 2006|
KRN7000 is reported to inhibit HBV replication in HBV transgenic mice. Anti-viral effects of KRN7000 can be expected in HBV, as the compound is able to induce not only IFN-alpha/beta but also IFN-gamma and TNF-alpha. In two clinical trials, KRN7000 was safe in both healthy volunteers and solid cancer patients; particularly, the compound has not been reported to show drug-related serious adverse events. A phase I/II trial is of significance in assessing the safety and efficacy of KRN7000 treatment for CHB patients.
The 300 microgram/m2 dose level, comparable to 10 microgram/kg, can be considered as the highest safe dose level for the phase I/II trial for CHB patients with 3 dose levels. Dose incrementation will be performed in a logarithmic manner: 0.1, 1 and 10 microgram/kg.
In the phase I trial for solid tumor patients, weekly administration of KRN7000 did not allow sufficient time for NKT cell recovery. As KRN7000 is reported to be an activating ligand for NKT cells, it is logical to assume that a dosing interval that provides time for recovery of NKT cells is optimal. In fact, cytokine production after repeating dosing, when NKT cells were hardly detected in the peripheral blood, was not observed. As it took approximately 4 weeks for NKT cells to recover to pre-dose levels after a single administration, monthly administration is now proposed for this trial.
|Erasmus MC, University Medical Center Rotterdam|
|Rotterdam, Netherlands, 3015GD|
|Principal Investigator:||Harry LA Janssen, MD, PhD||Dept. of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands|