Japanese EncephalitisPhase 2NCT00981630
Study of Live Attenuated ChimeriVax™-Japanese Encephalitis Vaccine
A Phase 2 study testing Live attenuated Japanese encephalitis virus in people with Japanese Encephalitis, run by Sanofi at 2 sites in Australia.
Trial summary
The purpose of this study is to assess the safety, tolerability, and immunogenicity of a new formulation of lyophilised ChimeriVax™-JE, given at three dose levels, compared with placebo. Read more about this study
- Who is it for?
- Ages 18 to 48 yearsHealthy volunteers can take part
- Conditions the study is for
- Japanese Encephalitis
- What is being tested?
- Live attenuated Japanese encephalitis virus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 2 sitesAustralia
- Study dates
- Nov 2004to Nov 2007
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 48 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All aspects of the protocol explained and written informed consent obtained from the participant.
- Aged ≥18 to < 49 years.
- In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.
- Participant must be available for the study duration, including all planned follow-up visits.
- Participant must agree to take the following precautions to avoid insect bites for 7 days following vaccination by using N,N-diethyl-meta-toluamide (DEET)-containing insect repellent, where appropriate.
- For female participants: Negative pregnancy tests at Screening and Day 0, in conjunction with a menstrual and contraceptive history indicating a low probability of pregnancy in the opinion of the physician. Females of childbearing potential will be required to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before randomisation and during the on-study phase to Day 30. Barrier methods of contraception will not be considered acceptable for study entry. Female participants of child-bearing potential will sign an agreement that contraception will be correctly practised during the specified periods and will specify the method used. Female participants unable to become pregnant must have this documented (e.g., tubal ligation, hysterectomy or postmenopausal [at least one year since last menstrual period]).
Who cannot join
- A history of vaccination or infection to Japanese encephalitis (JE) or yellow fever (YF) or other flaviviruses (including Japanese encephalitis, tick-borne encephalitis, St Louis encephalitis, West Nile virus, dengue fever, Murray Valley encephalitis). Previous vaccination will be determined by history (interview of subject).
- Previous or current military service.
- History of residence in or travel to flavivirus endemic areas in the tropics (Cape York region of Northern Queensland, India, Southeast Asia, Central America, Caribbean or South America) for periods of 4 weeks or more.
- Known or suspected immunodeficiency (e.g., human immunodeficiency virus [HIV] infection, primary immunodeficiency disorder, leukemia, lymphoma), use of immunosuppressive or antineoplastic drugs (corticosteroids > 10 mg prednisone, or equivalent, in the last three months or during the trial (up to Day 30).
- History of thymoma, thymic surgery (removal) or myasthenia gravis.
- Clinically significant abnormalities on laboratory assessment (i.e., meeting the mild, moderate or severe criteria described in the toxicity gradings for laboratory values).
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- Anaphylaxis or other serious adverse reactions characterised by urticaria or angioedema to foods, hymenoptera (bee family) stings, or drugs (including vaccines).
- Transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within six months of the Screening Visit or up to Day 30.
- Administration of another vaccine or antiviral within 30 days preceding the screening visit or up to Day 30 (these subjects will be rescheduled for vaccination at a later date).
- Physical examination indicating any clinically significant medical condition.
- Body temperature > 38.1°C (100.6°F) or acute illness within 3 days prior to inoculation (participant may be rescheduled).
- Intention to travel out of the area prior to the study visit on Day 30.
- Seropositive to hepatitis C virus or HIV or positive for Hepatitis B Surface Antigen.
- Lactation or intended pregnancy in female subjects.
- Excessive alcohol consumption, drug abuse, significant psychiatric illness.
- A known or suspected physiological or structural condition that compromises the integrity of the blood-brain barrier (e.g., significant hypertensive cerebrovascular disease, trauma, ischaemia, infection, inflammation of the brain).
- Intention to increase normal exercise routine, participate in contact sports or strenuous weight lifting or to initiate vigorous exercise from Screening until after Day 30.
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Study site
Adelaide, South Australia, 5000
Study site
Herston, Queensland, QLD 4006
About this study
Official title: Randomised, Double-blind, Placebo Controlled Phase II, Dose-ranging Study of the Safety, Tolerability and Immunogenicity of Live Attenuated ChimeriVax™-JE Vaccine (Lyophilised)
The purpose of this study is to assess the safety, tolerability, and immunogenicity of a new formulation of lyophilised ChimeriVax™-JE, given at three dose levels, compared with placebo.
Primary Objectives:
Read more
Safety:
- To obtain safety and tolerability data for a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers (18-49 years old).
Immunogenicity:
- To obtain data on the antibody response to a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers without prior Japanese encephalitis immunity.
- To assess the durability of immune response up to 12 months following a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels.
Read the detailed description
All participants will received a single dose of study vaccine, ChimeriVax™-JE or placebo on Day 0. The double-blind treatment phase will last 30 days, with follow-up visits at 6 and 12 months.
- Conditions
- Japanese Encephalitis
- Being tested
- Live attenuated Japanese encephalitis virus, ChimeriVax™ diluent (Placebo)
- Keywords
- Japanese Encephalitis, ChimeriVax™-JE Vaccine, Adult
- Medical subject headings
- Encephalitis, Japanese
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live attenuated Japanese encephalitis virusBiological
Also called ChimeriVax™-JE
0.5 mL,Subcutaneous
Live attenuated Japanese encephalitis virusBiological
Also called ChimeriVax™-JE
0.5 mL, Subcutaneous
Live attenuated Japanese encephalitis virusBiological
Also called ChimeriVax™-JE
0.5 mL, Subcutaneous
ChimeriVax™ diluent (Placebo)Biological
Also called Paricipants received a dose of ChimeriVax™ diluent at Day 0.
0.5 mL, Subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| ChimeriVax™-JE Dose Level 1 | Experimental | Participants received ChimeriVax™-JE (Japanese Encephalitis) a dose of 3.0 log10 Plaque-forming units (PFU) on Day 0. Receives: Biological: Live attenuated Japanese encephalitis virus |
| ChimeriVax™-JE Dose Level 2 | Experimental | Participants received ChimeriVax™-JE a dose of 4.0 log10 PFU on Day 0. Receives: Biological: Live attenuated Japanese encephalitis virus |
| ChimeriVax™-JE Dose Level 3 | Experimental | Participants received ChimeriVax™-JE a dose of 5.0 log10 PFU on Day 0. Receives: Biological: Live attenuated Japanese encephalitis virus |
| Placebo | Placebo comparator | Participants received ChimeriVax diluent, 0.5 mL on Day 0. Receives: Biological: ChimeriVax™ diluent (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains. Seroconversion was defined as a titer ≥ 1:20 at post vaccination timepoints for subjects who were seronegative at baseline, or ≥ 4 fold rise from baseline.
Measured: Day 11 and Day 30 post-vaccination
Number of Participants Who Seroconverted to Wild Type JE Virus Strains After Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains. Seroconversion was defined as a titer ≥ 1:20 at post vaccination time points for subjects who were seronegative at baseline, or ≥ 4 fold rise from baseline.
Measured: Day 30 post-vaccination
Number of Participants Reporting Solicited Local Injection Site and Treatment Related Adverse Events Post Vaccination With One of 3 Doses of ChimeriVax™-JE Vaccine or Placebo
Local Injection Site Adverse Events (AEs): Pain, Erythema, Reaction, Hemorrhage, Induration, Paresthesia. Treatment Related Systemic AEs: Fever, Chills, Malaise, Fatigue, Headache, Myalgia, Arthralgia, Nausea, Vomiting, Diarrhea, Rash. Other AEs as reported spontaneously.
Measured: Day 0 (post-vaccination) up to Day 30 post-vaccination
Secondary outcomes (3)
Geometric Mean Titers to Japanese Encephalitis (Homologous Virus) Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE virus strains.
Measured: Day 11 and Day 30 post-vaccination
Geometric Mean Titers to Japanese Encephalitis (Wild Type JE Virus Strains) Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
The Japanese Encephalitis (Wild Type JE Virus Strains) antibodies were measured using PRNT50 for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains.
Measured: Day 30 post-vaccination
Participants With Japanese Encephalitis (Homologous Virus) Seropositivity Over Time Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or Placebo
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE virus strains. Seropositivity was defined as a titer < 1:10.
Measured: Day 30 up to 12 months post-vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2009 (estimated)
- Study startNov 2004
- Primary completionFeb 2006
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Japanese EncephalitisStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Sanofi Pasteur Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981630
- Sponsor's protocol ID
- H-040-007
- Status last verified
- Nov 2012
- First submitted
- 21 Sep 2009
- Last updated
- 5 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Double-blind, Placebo Controlled Phase II, Dose-ranging Study of the Safety, Tolerability and Immunogenicity of Live Attenuated ChimeriVax™-JE Vaccine (Lyophilised)
- ClinicalTrials.gov ID
- NCT00981630
- Acronym / sponsor ID
- H-040-007
- Conditions
- Japanese Encephalitis
- Keywords
- Japanese Encephalitis, ChimeriVax™-JE Vaccine, Adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Nov 2004
- Primary completion
- Feb 2006 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 22 Sep 2009 (estimated)
- Results
- Posted 5 Dec 2012
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 study is to assess the safety, tolerability, and immunogenicity of a new formulation of lyophilised ChimeriVax™-JE, given at three dose levels, compared with placebo.
Primary Objectives:
Safety:
- To obtain safety and tolerability data for a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers (18-49 years old).
Immunogenicity:
- To obtain data on the antibody response to a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers without prior Japanese encephalitis immunity.
- To assess the durability of immune response up to 12 months following a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels.
Detailed description
All participants will received a single dose of study vaccine, ChimeriVax™-JE or placebo on Day 0. The double-blind treatment phase will last 30 days, with follow-up visits at 6 and 12 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ChimeriVax™-JE Dose Level 1 | Experimental | Biological: Live attenuated Japanese encephalitis virusParticipants received ChimeriVax™-JE (Japanese Encephalitis) a dose of 3.0 log10 Plaque-forming units (PFU) on Day 0. |
| ChimeriVax™-JE Dose Level 2 | Experimental | Biological: Live attenuated Japanese encephalitis virusParticipants received ChimeriVax™-JE a dose of 4.0 log10 PFU on Day 0. |
| ChimeriVax™-JE Dose Level 3 | Experimental | Biological: Live attenuated Japanese encephalitis virusParticipants received ChimeriVax™-JE a dose of 5.0 log10 PFU on Day 0. |
| Placebo | Placebo comparator | Biological: ChimeriVax™ diluent (Placebo)Participants received ChimeriVax diluent, 0.5 mL on Day 0. |
Who may qualify
- Ages
- 18 to 48 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- All aspects of the protocol explained and written informed consent obtained from the participant.
- Aged ≥18 to < 49 years.
- In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.
- Participant must be available for the study duration, including all planned follow-up visits.
- Participant must agree to take the following precautions to avoid insect bites for 7 days following vaccination by using N,N-diethyl-meta-toluamide (DEET)-containing insect repellent, where appropriate.
Key exclusion criteria (17 listed)
- A history of vaccination or infection to Japanese encephalitis (JE) or yellow fever (YF) or other flaviviruses (including Japanese encephalitis, tick-borne encephalitis, St Louis encephalitis, West Nile virus, dengue fever, Murray Valley encephalitis). Previous vaccination will be determined by history (interview of subject).
- Previous or current military service.
- History of residence in or travel to flavivirus endemic areas in the tropics (Cape York region of Northern Queensland, India, Southeast Asia, Central America, Caribbean or South America) for periods of 4 weeks or more.
- Known or suspected immunodeficiency (e.g., human immunodeficiency virus [HIV] infection, primary immunodeficiency disorder, leukemia, lymphoma), use of immunosuppressive or antineoplastic drugs (corticosteroids > 10 mg prednisone, or equivalent, in the last three months or during the trial (up to Day 30).
- History of thymoma, thymic surgery (removal) or myasthenia gravis.
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 |
|---|---|---|
| Live attenuated Japanese encephalitis virusAlso: ChimeriVax™-JE0.5 mL,Subcutaneous | Biological | ChimeriVax™-JE Dose Level 1 |
| Live attenuated Japanese encephalitis virusAlso: ChimeriVax™-JE0.5 mL, Subcutaneous | Biological | ChimeriVax™-JE Dose Level 2 |
| Live attenuated Japanese encephalitis virusAlso: ChimeriVax™-JE0.5 mL, Subcutaneous | Biological | ChimeriVax™-JE Dose Level 3 |
| ChimeriVax™ diluent (Placebo)Also: Paricipants received a dose of ChimeriVax™ diluent at Day 0.0.5 mL, Subcutaneous | Biological | Placebo |
Primary outcome
Number of Participants Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo
Time frame: Day 11 and Day 30 post-vaccination
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains. Seroconversion was defined as a titer ≥ 1:20 at post vaccination timepoints for subjects who were seronegative at baseline, or ≥ 4 fold rise from baseline.
Number of Participants Who Seroconverted to Wild Type JE Virus Strains After Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
Time frame: Day 30 post-vaccination
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains. Seroconversion was defined as a titer ≥ 1:20 at post vaccination time points for subjects who were seronegative at baseline, or ≥ 4 fold rise from baseline.
Number of Participants Reporting Solicited Local Injection Site and Treatment Related Adverse Events Post Vaccination With One of 3 Doses of ChimeriVax™-JE Vaccine or Placebo
Time frame: Day 0 (post-vaccination) up to Day 30 post-vaccination
Local Injection Site Adverse Events (AEs): Pain, Erythema, Reaction, Hemorrhage, Induration, Paresthesia. Treatment Related Systemic AEs: Fever, Chills, Malaise, Fatigue, Headache, Myalgia, Arthralgia, Nausea, Vomiting, Diarrhea, Rash. Other AEs as reported spontaneously.
3 secondary outcomes
Geometric Mean Titers to Japanese Encephalitis (Homologous Virus) Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
Time frame: Day 11 and Day 30 post-vaccination
Geometric Mean Titers to Japanese Encephalitis (Wild Type JE Virus Strains) Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
Time frame: Day 30 post-vaccination
Participants With Japanese Encephalitis (Homologous Virus) Seropositivity Over Time Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or Placebo
Time frame: Day 30 up to 12 months post-vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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.
Medical Director study director
Sanofi Pasteur Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Live attenuated Japanese encephalitis virus in people with Japanese Encephalitis, run by Sanofi at 2 sites in Australia.
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 6 inclusion and 17 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 5 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Yes. Results are posted in the registry (first posted 5 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo (time frame: Day 11 and Day 30 post-vaccination). The study lists 3 primary outcomes in all. 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 5 Dec 2012.