A Study of ChimeriVax™-JE Live Attenuated Vaccine in Healthy Adults

Japanese Encephalitis Clinical Trial

Official title:

Randomised, Double-blind, Phase 2 Study of the Safety, Immunogenicity and Duration of Immunity of ChimeriVax™-JE, Live Attenuated Vaccine in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00981175
• Other study ID #: H-040-005
• Status: Completed
• Phase: Phase 2
• First received: September 21, 2009
• Last updated: July 11, 2012
• Start date: April 2003
• Est. completion date: February 2008

Study information

• Verified date: July 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research CouncilUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, tolerability, immunogenicity, and duration of immunity of one or two doses of ChimeriVax™-JE vaccine separated by 5 or 6 months in adults.

Objectives:

Safety:

• Obtain safety and tolerability data of a single, fixed dose of ChimeriVax™-JE compared with a placebo in adult volunteers (≥ 18 to <55 years) without prior Japanese encephalitis (JE) vaccination.

Immunogenicity:

• Obtain data on the antibody response in adult volunteers following administration of ChimeriVax™-JE

• Assess the durability of the immune response in adult volunteers over 60 months following one or two doses of ChimeriVax™-JE.

Description:

Participants will receive ChimeriVax™-JE or diluent on Day 0 and diluent or ChimeriVax™-JE on Day 28. A subset of participants in each group will receive a booster dose of ChimeriVax™-JE at Month 6. Follow-up visits will occur at 12 and 24 months. Eligible participants will then enter the long-term immunogenicity follow-up period with visits at approximately 36, 48, and 60 months after Day 0. No safety data will be collected in the long-term immunogenicity follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: February 2008
• Est. primary completion date: June 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 54 Years

Eligibility

Inclusion Criteria :

At entry:

• All aspects of the protocol explained and written informed consent obtained from the subject.

• Aged = 18 to < 55 years.

• In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.

• Subject must be available for the study duration, including all planned follow-up visits.

• Has the subject agreed to take the following precautions to avoid insect bites for 7 days following vaccination: (a) wear long-sleeved shirts and trousers?; (b) apply N,N-Diethyl-meta-toluamide (DEET)-containing insect repellents?; (c) Sleep in screened enclosures?

• For female subjects of childbearing potential: Negative serum pregnancy tests. An efficacious hormonal (i.e., oral, implantable or injectable) or barrier method of birth control must be used at least 1 month before Screening and Month 6 and at least 1 month after Day 28 and Month 6. These subjects will sign an agreement that birth control will be practised during the specified periods and will specify the method used. Female subjects unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).

For long-term immunogenicity follow-up period:

• Subject received an initial dose of ChimeriVax™-JE, has a baseline (Day 0) sample and at least one post-vaccination evaluable serological specimen for antibody analysis.

• All aspects of the Long-term Immunogenicity Follow-up Period explained and updated written informed consent obtained from the subject.

• In good general health, without significant medical history that may affect the efficacy endpoints or the ability to take blood samples.

Exclusion Criteria :

• A history of vaccination to Japanese encephalitis (JE). Previous vaccination will be determined by history (interview of subject) and/or by reviewing the subject's vaccination card or other official documentation (either a history of or documentation of vaccination fulfils the criterion for exclusion).

• 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, for more than 14 days in the last three months).

• Clinically significant abnormalities on laboratory assessment.

• Serious adverse reactions characterised by urticaria or angioedema to a prior vaccine.

• 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 56.

• Administration of another vaccine within 30 days preceding the screening visit or up to Day 56 (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 (subject may be rescheduled).

• Intention to travel out of the area prior to the study visit on Day 56.

• Seropositive to hepatitis C virus (HCV) or HIV or positive for hepatitis B (HBV) (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, ischemia, infection, inflammation of the brain).

For long-term immunogenicity follow-up period:

• History of Yellow Fever or out of study JE vaccination or known flavivirus infection since receiving ChimeriVax™-JE vaccination on Day 0 or Day 28 (during double-blind treatment period of the study). Yellow Fever/JE vaccination or flavivirus infection will be determined by history (interview of subject) and/or by reviewing the subject's medical records. Please note subjects who were flavivirus positive at Day 0 will be allowed to enrol on the study.

• Participation in another JE clinical study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Japanese
• Japanese Encephalitis

Intervention

Biological:
• Live attenuated Japanese encephalitis virus, then ChimeriVax diluent
ChimeriVax™-JE, 0.5 mL subcutaneous on Day 0; ChimeriVax diluent 0.5 mL subcutaneous on Day 28
• ChimeriVax diluent, then Live attenuated Japanese encephalitis virus
ChimeriVax diluent, 0.5 mL subcutaneous on Day 0 and ChimeriVax™-JE, 0.5 mL subcutaneous on Day 28.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Australia, 

References & Publications (1)

Nasveld PE, Ebringer A, Elmes N, Bennett S, Yoksan S, Aaskov J, McCarthy K, Kanesa-thasan N, Meric C, Reid M. Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine: randomized, double-blind, 5-year phase II study in healthy ad — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Seroconversion to Homologous ChimeriVax-JE Virus Strain After a Single Dose of Chimerivax™-JE and Placebo Dose	Assay by 50% Plaque Reduction Neutralization Test (PRNT50) Seroconversion: PRNT50 = 10 and PRNT50 = 20. Assessed in all participants who received ChimeriVax™-JE vaccine on Day 0 and Day 28.	Day 28 post-vaccination	No
Primary	Number of Participants Reporting Injection Site Treatment Emergent Adverse Events Post-Vaccination With ChimeriVax™-JE or Placebo at Day 0 and Day 28, and Following a Booster of ChimeriVax™-JE at Month 6 in a Subset of the Study Population.	Injection Site Treatment Emergent Adverse Events: Pain, Reaction Not Otherwise Specified (NOS), Erythema, Swelling, Bruising, Nodule, Pigmentation Changes, Pruritus were assessed in all participants for up to 28 days post-Vaccination.	Days 0 to 28 post-vaccination	No
Secondary	Number of Participants With Seroconversion to Homologous ChimeriVax™-JE Virus Strain After a Single Dose of Chimerivax™-JE and Placebo Followed by a Booster Vaccine Dose.	Assay by 50% Plaque Reduction Neutralization Test (PRNT50) Seroconversion: PRNT50 = 10 and PRNT50 = 20. Assessed in all participants who received ChimeriVax™-JE vaccine on Day 0 and Day 28 and pre- and post-Booster vaccination.	Month 6 pre- and post-vaccination	No
Secondary	Number of Participants With Seroconversion to Homologous ChimeriVax™-JE Virus Strain After a Single Dose of Chimerivax™-JE and Placebo Followed or Not by a Booster Vaccine Dose at 6 Month.	Assay by 50% Plaque Reduction Neutralization Test (PRNT50) Seroconversion: PRNT50 = 10 and PRNT50 = 20. Assessed in all participants who received ChimeriVax™-JE vaccine on Day 0 and Day 28 and followed or not by a booster vaccine dose at 6 month.	Month 12 post-vaccination	No
Secondary	Number of Participants With Seroconversion to Homologous ChimeriVax-JE Virus Strain After a Single Dose of Chimerivax™-JE and Placebo Followed or Not by a Booster Vaccine Dose at 6 Month.	Assay by 50% Plaque Reduction Neutralization Test (PRNT50) Seroconversion: PRNT50 = 10 and PRNT50 = 20. Assessed in all participants who received ChimeriVax™-JE vaccine on Day 0 and Day 28 and followed or not by a booster vaccine dose at month 24.	Month 24 post-vaccination	No
Secondary	Number of Participants Reporting Treatment Emergent Adverse Events Recorded as Possibly, Probably, or Definitely Related to Study Treatment.	Treatment emergent adverse events were assessed in all participants receiving ChimeriVax-JE Vaccine, Diluent (Placebo), or Booster Vaccination.	Day 0 up to 28 post-vaccination	No

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