KRN7000 in Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by:
Foundation for Liver Research
ClinicalTrials.gov Identifier:
NCT00363155
First received: August 10, 2006
Last updated: NA
Last verified: August 2006
History: No changes posted
  Purpose

The purpose of this trial is to determine the safety, tolerability and effectiveness of KRN7000 for chronic hepatitis B infection.


Condition Intervention Phase
Hepatitis B, Chronic
Drug: KRN7000
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis B Infection

Resource links provided by NLM:


Further study details as provided by Foundation for Liver Research:

Primary Outcome Measures:
  • To determine safety and tolerability

Secondary Outcome Measures:
  • To evaluate effectiveness in reducing HBV DNA load
  • To evaluate effectiveness in inducing immunological responses
  • TO evaluate effectiveness in normalization of ALT

Estimated Enrollment: 28
Study Start Date: March 2003
Estimated Study Completion Date: July 2006
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic hepatitis B (confirmed by a liver biopsy performed within 3 years prior to the screenings visit and HBV DNA in serum >10E5 copies/ml at the screenings visit).
  • ALT > 1.2 x ULN on two occasions documented within 8 weeks before initiation of treatment.
  • Able and likely to attend regularly for treatment and follow-up.
  • Written informed consent.
  • Adequate contraception for males and females during treatment and follow-up (written confirmation).

Exclusion Criteria:

  • Patients with evidence of cirrhosis.
  • Decompensated liver disease, as marked by: bilirubin greater than 20 micromol/L or serum albumin <35 g/L or prothrombin time greater than 3 seconds prolonged or Quick test below 70% or history of bleeding esophageal varices, ascites or hepatic encephalopathy.
  • Systemic IFN treatment, systemic antiviral agents, systemic corticosteroids, immune suppressive treatment or any investigational drug within 3 months of entry to this protocol.
  • Patients with ALT levels greater than 10 times ULN will not be enrolled but may be followed until three consecutive determinations within 2 months are below this level.
  • Pregnancy, or in women of child-bearing potential or in spouses of such women, inability to practice adequate contraception.
  • Significant systemic or major illnesses other than liver disease, including congestive heart failure, ischemic heart disease, angina pectoris, cerebrovascular disease, renal failure (creatinine clearance less than 50 ml/min), organ transplantation, serious psychiatric disease or depression, anaphylactic disorder.
  • Pre-existing severe cytopenia; Hb<7 mmol/L, WBC <3x10E9/L, Plt <100x10E9/L, Lymphocyte <0.5x10E9/L.
  • Any history or presence of autoimmune disease.
  • Evidence of hepatocellular carcinoma; alpha-fetoprotein (AFP) levels greater than 50 ng/ml and ultrasound (or other imaging study) within 6 months prior to the entry demonstrating a mass suggestive of liver cancer.
  • Human immunodeficiency virus infection, as shown by presence of anti-HIV antibody.
  • Patients with cerebroside metabolite abnormalities (e.g. Gaucher's disease).
  • Other acquired or inherited causes of liver disease: hepatitis C, hepatitis D, alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune liver disease, Wilson's disease, hemochromatosis, alpha-1-antitrypsin deficiency.
  • Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00363155

Locations
Netherlands
Erasmus MC, University Medical Center Rotterdam
Rotterdam, Netherlands, 3015GD
Sponsors and Collaborators
Foundation for Liver Research
Investigators
Principal Investigator: Harry LA Janssen, MD, PhD Dept. of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00363155     History of Changes
Other Study ID Numbers: KRN7000/02-B01
Study First Received: August 10, 2006
Last Updated: August 10, 2006
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Foundation for Liver Research:
chronic
hepatitis b

Additional relevant MeSH terms:
Hepatitis B, Chronic
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
KRN 7000
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014