Eastern Equine Encephalitis
Conditions
Keywords
EEE
Brief summary
This study is designed to determine the safety and immunogenicity of Eastern Equine Encephalitis (EEE) Vaccine.
Detailed description
This was an open-label, vaccine study of Eastern Equine Encephalitis Vaccine, Inactivated Dried, EEE, TSI-GSD 104 in healthy, adult subjects. No concurrent control group was used. The controls used in this study to assess immunogenicity were historical PRNT80 values obtained in past studies of the EEE vaccine. Rates of adverse events (AEs) were tabulated by relationship to product administration and severity. The primary objectives are to assess the safety of Eastern Equine Encephalitis Vaccine, Inactivated, Dried EEE, TSI GSD 104, and to assess immunogenicity of Eastern Equine Encephalitis Vaccine, Inactivated, Dried EEE, TSI GSD 104.
Interventions
BIOLOGICALInactivated, Dried, TSI-GSD 104, EEE
Subjects will receive 0.5ml SQ, as a two-dose primary series (days 0 and 28) and 0.1ml, as a mandatory booster dose at 6 months. A booster dose may be administered before 6 months if PRNT80 is \< 1:40 after day 28. Up to four booster doses may be given in any 1-year period.
Sponsors
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* At least 18 years old. * EEE PRNT80 ≤ 1:20. * EEE PRNT80 ≤ 1:40 for booster series * (females) Negative pregnancy test on the same day before vaccination. * Not planning pregnancy for 3 months. * At risk for exposure to virulent EEE virus (with up-to-date risk assessment). * Up-to-date (within 1 year) physical examination/tests. * Sign and date the approved informed consent. * Willing to return for all follow-up visits. * Agree to report adverse events (AE) up to 28 days after each vaccination.
Exclusion criteria
* Over 65 years of age (for Primary Immunization). * Clinically significant abnormal lab results including evidence of Hepatitis C, Hepatitis B carrier state, or elevated (2X normal) liver function tests. * History of immunodeficiency or current treatment with immunosuppressive medication. * (females) Currently breastfeeding. * Confirmed human immunodeficiency virus (HIV) titer. * Any known allergies to components of the vaccine. * A medical condition that, in the judgment of the Principal Investigator (PI), would impact subject safety (i.e.-vaccination or exposure to another Alphavirus). * Administration of any IND product or live vaccine within 28 days of EEE. * Any unresolved AEs resulting from a previous immunization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates of Pre-Month 6 PRNT80 Titers | Pre-month 6 | Subject response rates for PRNT80 titers of pre-month 6. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. |
| Subject Response Rates for PRNT80 Titers | 5 years | Subject response rates for PRNT80 titers for vaccinations and all boosters. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. Four to 5 weeks for primary vaccinations (3) and up to four boost doses in 1 year period for a total duration of up to 5 years (anticipated duration of study execution). |
| Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Post dose 2, days 21-35 | Subject response rates for PRNT80 titers for post dose 2, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. |
| Response Rates of Annual (11-13 Months) PRNT80 Titers | Months 11-13 | Subject annual response rates for PRNT80 titers for months 11-13. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. |
| Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Post month 6, days 21-35 | Subject response rates for PRNT80 titers for post month 6, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. |
| Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Post booster 1, days 21-35 | Subject response rates for PRNT80 titers for post booster 1, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subject Experiencing Local and Systemic Adverse Events | vaccination/booster days 0-28 for up to 5 years | Number of subjects of who experienced and didn't experience local and systemic adverse events after vaccination and booster. |
Countries
United States
Participant flow
Recruitment details
138 subjects were enrolled at Special Immunizations Clinic, Division of Medicine, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD
Participants by arm
| Arm | Count |
|---|---|
| Vaccination Inactivated, Dried, TSI-GSD 104, EEE
Inactivated, Dried, TSI-GSD 104, EEE: Subjects will receive 0.5ml SQ, as a two-dose primary series (days 0 and 28) and 0.1ml, as a mandatory booster dose at 6 months. A booster dose may be administered before 6 months if PRNT80 is \< 1:40 after day 28. Up to four booster doses may be given in any 1-year period. | 138 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to follow up | 3 |
| Overall Study | No longer at risk of exposure | 39 |
| Overall Study | Non-compliance | 1 |
| Overall Study | Relocation | 36 |
| Overall Study | Screen failures | 2 |
| Overall Study | Withdrawal by Subject | 18 |
Baseline characteristics
| Characteristic | Vaccination |
|---|---|
| Age, Continuous | 39.0 Years of age STANDARD_DEVIATION 10.23 |
| Race/Ethnicity, Customized Race : Asian | 5 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 3 Participants |
| Race/Ethnicity, Customized Race : Other | 4 Participants |
| Race/Ethnicity, Customized Race : White | 126 Participants |
| Region of Enrollment United States | 138 participants |
| Sex: Female, Male Female | 59 Participants |
| Sex: Female, Male Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 136 |
| other Total, other adverse events | 73 / 136 |
| serious Total, serious adverse events | 5 / 136 |
Outcome results
Primary
Response Rates of Annual (11-13 Months) PRNT80 Titers
Subject annual response rates for PRNT80 titers for months 11-13. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population.
Time frame: Months 11-13
Population: Only observations or specimens collected according to the protocol were included in the analyses
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Responders | Year: 2008 | 11 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Responders | Year: 2009 | 3 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Responders | Year: 2010 | 12 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Responders | Year: 2011 | 6 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Responders | Year: 2013 | 5 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Responders | Year: 2014 | 2 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Non-responders | Year: 2008 | 4 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Non-responders | Year: 2009 | 6 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Non-responders | Year: 2010 | 0 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Non-responders | Year: 2011 | 2 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Non-responders | Year: 2013 | 2 Participants |
| Vaccination | Response Rates of Annual (11-13 Months) PRNT80 Titers | Non-responders | Year: 2014 | 0 Participants |
Primary
Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers
Subject response rates for PRNT80 titers for post booster 1, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population.
Time frame: Post booster 1, days 21-35
Population: Only observations or specimens collected according to the protocol were included in the analyses
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2008 | 34 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2009 | 23 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2010 | 11 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2011 | 3 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2013 | 6 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2014 | 3 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Responders | Year: 2015 | 2 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2008 | 10 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2009 | 13 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2010 | 1 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2011 | 0 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2013 | 0 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2014 | 1 Participants |
| Vaccination | Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Non-responders | Year: 2015 | 0 Participants |
Primary
Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers
Subject response rates for PRNT80 titers for post dose 2, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population.
Time frame: Post dose 2, days 21-35
Population: Only observations or specimens collected according to the protocol were included in the analyses
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Responders | Year: 2011 | 12 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Responders | Year: 2013 | 5 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Responders | Year: 2008 | 8 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Responders | Year: 2009 | 4 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Responders | Year: 2010 | 10 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Responders | Year: 2014 | 2 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Non-responders | Year: 2008 | 14 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Non-responders | Year: 2009 | 6 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Non-responders | Year: 2010 | 3 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Non-responders | Year: 2011 | 0 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Non-responders | Year: 2013 | 3 Participants |
| Vaccination | Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Non-responders | Year: 2014 | 0 Participants |
Primary
Response Rates of Post Month 6: Day 21-35 PRNT80 Titers
Subject response rates for PRNT80 titers for post month 6, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population.
Time frame: Post month 6, days 21-35
Population: Only observations or specimens collected according to the protocol were included in the analyses
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2008 | 2 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2009 | 16 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2010 | 9 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2011 | 11 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2012 | 2 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2013 | 1 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2014 | 6 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Responders | Year: 2015 | 2 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2008 | 0 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2009 | 8 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2010 | 1 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2011 | 1 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2012 | 0 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2013 | 0 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2014 | 1 Participants |
| Vaccination | Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Non-responders | Year: 2015 | 0 Participants |
Primary
Response Rates of Pre-Month 6 PRNT80 Titers
Subject response rates for PRNT80 titers of pre-month 6. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population.
Time frame: Pre-month 6
Population: Only observations or specimens collected according to the protocol were included in the analyses
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Responders | Year: 2008 | 7 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Responders | Year: 2009 | 3 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Responders | Year: 2010 | 8 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Responders | Year: 2011 | 6 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Responders | Year: 2013 | 3 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Responders | Year: 2014 | 1 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Non-responders | Year: 2008 | 13 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Non-responders | Year: 2009 | 6 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Non-responders | Year: 2010 | 4 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Non-responders | Year: 2011 | 4 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Non-responders | Year: 2013 | 5 Participants |
| Vaccination | Response Rates of Pre-Month 6 PRNT80 Titers | Non-responders | Year: 2014 | 1 Participants |
Primary
Subject Response Rates for PRNT80 Titers
Subject response rates for PRNT80 titers for vaccinations and all boosters. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. Four to 5 weeks for primary vaccinations (3) and up to four boost doses in 1 year period for a total duration of up to 5 years (anticipated duration of study execution).
Time frame: 5 years
Population: Only observations or specimens collected according to the protocol were included in the analyses
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vaccination | Subject Response Rates for PRNT80 Titers | Post booster 4, Day 21-35 | 7 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Post dose 2: Day 21-35 | 39 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Pre-month 6 | 28 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Post month 6, Day 21-35 | 48 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Post booster 1, Day 21-35 | 79 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Post booster 2, Day 21-35 | 24 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Post booster 3, Day 21-35 | 9 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Post booster 5, Day 21-35 | 3 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Annual (11-13 months) | 37 Participants |
| Vaccination | Subject Response Rates for PRNT80 Titers | Closeout | 75 Participants |
Secondary
Number of Subject Experiencing Local and Systemic Adverse Events
Number of subjects of who experienced and didn't experience local and systemic adverse events after vaccination and booster.
Time frame: vaccination/booster days 0-28 for up to 5 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vaccination | Number of Subject Experiencing Local and Systemic Adverse Events | No AEs: Male subjects | 19 Participants |
| Vaccination | Number of Subject Experiencing Local and Systemic Adverse Events | No AEs: Female subjects | 10 Participants |
| Vaccination | Number of Subject Experiencing Local and Systemic Adverse Events | Had AEs: Male subjects | 18 Participants |
| Vaccination | Number of Subject Experiencing Local and Systemic Adverse Events | Had AEs: Female subjects | 20 Participants |
| Vaccination - Booster | Number of Subject Experiencing Local and Systemic Adverse Events | Had AEs: Female subjects | 26 Participants |
| Vaccination - Booster | Number of Subject Experiencing Local and Systemic Adverse Events | No AEs: Male subjects | 47 Participants |
| Vaccination - Booster | Number of Subject Experiencing Local and Systemic Adverse Events | Had AEs: Male subjects | 30 Participants |
| Vaccination - Booster | Number of Subject Experiencing Local and Systemic Adverse Events | No AEs: Female subjects | 29 Participants |