Hepatitis B, ChronicPhase 1/2NCT00363155
KRN7000 in Chronic Hepatitis B
A Phase 1/2 study testing KRN7000 in people with Hepatitis B, Chronic, run by Foundation for Liver Research at 1 site in Netherlands.
Trial summary
The purpose of this trial is to determine the safety, tolerability and effectiveness of KRN7000 for chronic hepatitis B infection. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- KRN7000
- How many people
- 28 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2003to Jul 2006
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Erasmus MC, University Medical Center Rotterdam
Rotterdam, 3015GD
About this study
Official title: Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis B Infection
The purpose of this trial is to determine the safety, tolerability and effectiveness of KRN7000 for chronic hepatitis B infection.
Read the 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.
- Conditions
- Hepatitis B, Chronic
- Being tested
- KRN7000
- Keywords
- chronic, hepatitis b
- Medical subject headings
- Hepatitis B, Chronic, Bronchiolitis Obliterans Syndrome, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRN7000Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine safety and tolerability
Secondary outcomes (3)
To evaluate effectiveness in reducing HBV DNA load
To evaluate effectiveness in inducing immunological responses
TO evaluate effectiveness in normalization of ALT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2006 (estimated)
- Study startMar 2003
- Study completionJul 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 28 participants
Sponsor and investigators
- Lead sponsor
- Foundation for Liver Research
- Sponsor type
- University, hospital or other
- Investigators
- Harry LA Janssen, MD, PhD, Principal investigator, Dept. of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00363155
- Sponsor's protocol ID
- KRN7000/02-B01
- Status last verified
- Aug 2006
- First submitted
- 10 Aug 2006
- Last updated
- 15 Aug 2006
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of KRN7000 in Patients With Chronic Hepatitis B Infection
- ClinicalTrials.gov ID
- NCT00363155
- Acronym / sponsor ID
- KRN7000/02-B01
- Conditions
- Hepatitis B, Chronic
- Keywords
- chronic, hepatitis b
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants
- Lead sponsor
- Foundation for Liver ResearchUniversity, hospital or other
- Study start
- Mar 2003
- Study completion
- Jul 2006
- First posted
- 15 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to determine the safety, tolerability and effectiveness of KRN7000 for chronic hepatitis B infection.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KRN7000 | Drug | – |
Primary outcome
To determine safety and tolerability
3 secondary outcomes
To evaluate effectiveness in reducing HBV DNA load
To evaluate effectiveness in inducing immunological responses
TO evaluate effectiveness in normalization of ALT
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2006.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harry LA Janssen, MD, PhD principal investigator
Dept. of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KRN7000 in people with Hepatitis B, Chronic, run by Foundation for Liver Research at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine safety and tolerability. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2006.