Chikungunya Virus Infection
Conditions
Keywords
VLA1553, Chikungunya Virus Infection, CHIKV, Live-attenuated Chikungunya virus vaccine
Brief summary
This was a prospective, randomized, double-blinded, multicenter, pivotal clinical study evaluating the final dose of VLA1553 (1 x10E4 TCID50 per dose) in comparison to a placebo control. The final dose of VLA1553 or control was administered as single immunization on Day 1. Overall, 4.128 male and female subjects aged 18 years and above were randomized into the study.
Detailed description
This was a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study and 4.128 participants aged 18 years or above were randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The final dose of lyophilized VLA1553 or placebo was administered as a single intramuscular immunization. Subjects in this study were stratified into two age strata of 18 to 64 years and 65 years of age or above. The primary objective of the study was to evaluate the immunogenicity and safety of the final dose of VLA1553 28 days following the single immunization. Immunogenicity evaluations in the immunogenicity subset included the proportion of subjects with seroprotective neutralizing CHIKV antibody titers above a surrogate threshold indicative of protection. The surrogate of protection reasonably likely to predict clinical benefit has been established in non-human primate passive transfer studies using human sera from the Phase 1 study and was supported by sero-epidemiological studies. Safety data collection and immunogenicity were assessed until Month 6. The first enrolled and randomized 501 subjects comprised the immunogenicity subset.
Interventions
BIOLOGICALVLA1553
Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose
BIOLOGICALPlacebo
Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Sponsors
Valneva Austria GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. 18 years of age or above on the Day of screening 2. able to provide informed consent 3. generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests 4. for women of childbearing potential: 1. practiced an adequate method of contraception during 30 days before screening 2. negative serum or urine pregnancy test at screening 3. agreed to employ adequate birth control measures for the first three months post-vaccination. Main
Exclusion criteria
1. CHIKV infection in the past, including suspected CHIKV infection; was taking medication or other treatment for unresolved symptoms attributed to a previous CHIKV infection; or had participated in a clinical study involving an investigational CHIKV vaccine 2. acute or recent infection 3. Subject tested positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV); 4. live virus vaccine within 28 days or inactivated vaccine within 14 days prior to vaccination in this study or planned to receive a vaccine within 28 days or 14 days after vaccination, respectively 5. abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator which pose a risk for participation in the study 6. medical history of or currently had acute or progressive, unstable or uncontrolled clinical conditions that posed a risk for participation in the study 7. history of immune-mediated or clinically relevant arthritis / arthralgia 8. history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there had been surgical excision or treatment more than 5 years ago that was considered to have achieved a cure, the subject could be enrolled. 9. known or suspected defect of the immune system, such as subjects with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno-suppressive therapy within 4 weeks prior to vaccination. 10. history of any vaccine related contraindicating event (e.g., anaphylaxis, allergy to components of the candidate vaccine, other known contraindications) 11. with clinical conditions representing a contraindication to intramuscular vaccination and blood draws 12. pregnant or lactating at the time of enrollment 13. Donation of blood, blood fractions or plasma within 30 days or received blood-derived products (e.g. plasma) within 90 days prior to vaccination in this study or planned to donate blood or used blood products until Day 180 of the study 14. rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating 15. known or suspected problem with alcohol or drug abuse as determined by the Investigator 16. any condition that, in the opinion of the Investigator, could compromise the subjects well-being, interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study; 17. committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities) 18. Participation in another clinical study involving an investigational medicinal product (IMP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IMP, or device during the course of this study 19. member of the team conducting the study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the Investigator or site personnel conducting the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination | on Day 29 after single vaccination | Seroprotection rate, based on a surrogate of protection agreed with FDA Assay used for analysis was based on µPRNT (Micro Plaque Reduction Neutralization Test). Participants at pre-selected sites were included, if they had available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seroprotective CHIKV Antibody Level | Until Day 180 | Seroprotection rate, based on a surrogate of protection agreed with FDA Seroprotective CHIKV Antibody Level Defined as μPRNT (Micro Plaque Reduction Neutralization Test) for Baseline Negative Subjects |
| Number of Participants With Seroconversion | Until Day 180 | Seroconversion was defined as CHIKV-specific neutralizing antibody titer of ≥ 20 based on µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects |
| Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | until Day 180 | Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline |
| Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | until Day 180 | Number of Participants Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline |
| Unsolicited AEs | Until Day 29 | Number of Participants with Unsolicited Adverse Events |
| Solicited Injection Site AEs | within 10 days post-vaccination | Number of Participants with solicited injection site reactions |
| CHIKV-specific Neutralizing Antibody Titers | Until Day 180 | CHIKV-specific Neutralizing Antibody Titers on Day 8, and Day 29 Postvaccination as Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) Assay |
| Adverse Events | until Day 180 | Number of Participants with any Adverse Events |
| Related Adverse Events | until Day 180 | Number of Participants with any related Adverse Events |
| Serious Adverse Event | until Day 180 | Number of Participants with any Serious Adverse Events |
| Related Serious Adverse Event | until Day 180 | Number of Participants with any Related Serious Adverse Events |
| Adverse Event of Special Interest | within 21 days post-vaccination | Number of Participants with any Adverse Event of Special Interest AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: 1. Fever (≥38.0°C \[100.4°F\] measured orally) and 2. Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus \[foot plant\] and edema of the face and extremities), polyadenopathies; and 3. Onset of symptoms 2 to 21 days after vaccination and 4. Duration of event ≥3 days. |
| Related Adverse Event of Special Interest | within 21 days post-vaccination | Number of Participants with any Related Adverse Event of Special Interest AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: 1. Fever (≥38.0°C \[100.4°F\] measured orally) and 2. Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus \[foot plant\] and edema of the face and extremities), polyadenopathies; and 3. Onset of symptoms 2 to 21 days after vaccination and 4. Duration of event ≥3 days. |
| Solicited Systemic AEs | within 10 days post-vaccination | Number of Participants with solicited systemic reactions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VLA1553 VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose | 3,082 |
| Placebo Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo | 1,033 |
| Total | 4,115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 186 | 63 |
| Overall Study | Physician Decision | 8 | 2 |
| Overall Study | subject has been out of town | 1 | 0 |
| Overall Study | Subject in another study | 1 | 1 |
| Overall Study | subject is incarcerated | 2 | 0 |
| Overall Study | subject is relocating | 12 | 4 |
| Overall Study | Withdrawal by Subject | 145 | 41 |
Baseline characteristics
| Characteristic | Placebo | Total | VLA1553 |
|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 15.59 | 45.0 years STANDARD_DEVIATION 15.47 | 45.1 years STANDARD_DEVIATION 15.44 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 Participants | 32 Participants | 27 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants | 68 Participants | 51 Participants |
| Race/Ethnicity, Customized Black or African American | 122 Participants | 573 Participants | 451 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 5 Participants | 18 Participants | 13 Participants |
| Race/Ethnicity, Customized Other | 31 Participants | 115 Participants | 84 Participants |
| Race/Ethnicity, Customized White | 853 Participants | 3309 Participants | 2456 Participants |
| Sex: Female, Male Female | 569 Participants | 2251 Participants | 1682 Participants |
| Sex: Female, Male Male | 464 Participants | 1864 Participants | 1400 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3,082 | 1 / 1,033 |
| other Total, other adverse events | 1,721 / 3,082 | 373 / 1,033 |
| serious Total, serious adverse events | 46 / 3,082 | 8 / 1,033 |
Outcome results
Primary
Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination
Seroprotection rate, based on a surrogate of protection agreed with FDA Assay used for analysis was based on µPRNT (Micro Plaque Reduction Neutralization Test). Participants at pre-selected sites were included, if they had available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response.
Time frame: on Day 29 after single vaccination
Population: The Per-Protocol population used for immunogenicity analyses, is based on participants without major protocol deviations that could impact the immune response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination | 204 Participants |
| Placebo 18-64 Years | Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination | 0 Participants |
| VLA1553 ≥65 Years | Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination | 59 Participants |
| Placebo ≥65 Years | Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination | 0 Participants |
Secondary
Adverse Event of Special Interest
Number of Participants with any Adverse Event of Special Interest AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: 1. Fever (≥38.0°C \[100.4°F\] measured orally) and 2. Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus \[foot plant\] and edema of the face and extremities), polyadenopathies; and 3. Onset of symptoms 2 to 21 days after vaccination and 4. Duration of event ≥3 days.
Time frame: within 21 days post-vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Adverse Event of Special Interest | 10 Participants |
| Placebo 18-64 Years | Adverse Event of Special Interest | 1 Participants |
Secondary
Adverse Events
Number of Participants with any Adverse Events
Time frame: until Day 180
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VLA1553 18-64 Years | Adverse Events | Mild | 1287 Participants |
| VLA1553 18-64 Years | Adverse Events | Moderate | 532 Participants |
| VLA1553 18-64 Years | Adverse Events | Severe | 104 Participants |
| Placebo 18-64 Years | Adverse Events | Mild | 336 Participants |
| Placebo 18-64 Years | Adverse Events | Moderate | 112 Participants |
| Placebo 18-64 Years | Adverse Events | Severe | 14 Participants |
Secondary
CHIKV-specific Neutralizing Antibody Titers
CHIKV-specific Neutralizing Antibody Titers on Day 8, and Day 29 Postvaccination as Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) Assay
Time frame: Until Day 180
Population: The Per-Protocol population used for immunogenicity analyses, is based on participants without major protocol deviations that could impact the immune response.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| VLA1553 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 2 - Day 8 | 13.6 Antibody Titers |
| VLA1553 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 3 - Day 29 | 3273.7 Antibody Titers |
| VLA1553 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 4 - Day 85 | 1068.7 Antibody Titers |
| VLA1553 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 5 - Day 180 | 755.1 Antibody Titers |
| Placebo 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 3 - Day 29 | 10.1 Antibody Titers |
| Placebo 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 4 - Day 85 | 10.0 Antibody Titers |
| Placebo 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 5 - Day 180 | 10.0 Antibody Titers |
| Placebo 18-64 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 2 - Day 8 | 10.2 Antibody Titers |
| VLA1553 ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 4 - Day 85 | 1140.9 Antibody Titers |
| VLA1553 ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 3 - Day 29 | 3688.8 Antibody Titers |
| VLA1553 ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 5 - Day 180 | 742.8 Antibody Titers |
| VLA1553 ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 2 - Day 8 | 13.4 Antibody Titers |
| Placebo ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 5 - Day 180 | 10.0 Antibody Titers |
| Placebo ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 3 - Day 29 | 10.0 Antibody Titers |
| Placebo ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 2 - Day 8 | 10.0 Antibody Titers |
| Placebo ≥65 Years | CHIKV-specific Neutralizing Antibody Titers | Visit 4 - Day 85 | 10.7 Antibody Titers |
Secondary
Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline
Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline
Time frame: until Day 180
Population: The Per-Protocol population used for immunogenicity analyses, is based on participants without major protocol deviations that could impact the immune response.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VLA1553 18-64 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 3 - Day 29 | 460.27 fold increase | Standard Deviation 384.052 |
| VLA1553 18-64 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 5 - Day 180 | 108.81 fold increase | Standard Deviation 97.238 |
| Placebo 18-64 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 5 - Day 180 | 1.00 fold increase | Standard Deviation 0 |
| Placebo 18-64 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 3 - Day 29 | 1.02 fold increase | Standard Deviation 0.14 |
| VLA1553 ≥65 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 3 - Day 29 | 507.70 fold increase | Standard Deviation 412.467 |
| VLA1553 ≥65 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 5 - Day 180 | 102.09 fold increase | Standard Deviation 79.433 |
| Placebo ≥65 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 3 - Day 29 | 1.00 fold increase | Standard Deviation 0 |
| Placebo ≥65 Years | Fold Change of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline | Visit 5 - Day 180 | 1.00 fold increase | Standard Deviation 0 |
Secondary
Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline
Number of Participants Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline
Time frame: until Day 180
Population: The Per-Protocol population used for immunogenicity analyses, is based on participants without major protocol deviations that could impact the immune response.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 4-fold increase | 205 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 8-fold increase | 205 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 16-fold increase | 204 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 64-fold increase | 200 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 4-fold increase | 181 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 8-fold increase | 181 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 16-fold increase | 177 Participants |
| VLA1553 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 64-fold increase | 106 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 8-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 4-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 8-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 64-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 16-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 64-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 16-fold increase | 0 Participants |
| Placebo 18-64 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 4-fold increase | 0 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 16-fold increase | 55 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 16-fold increase | 59 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 64-fold increase | 57 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 4-fold increase | 57 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 8-fold increase | 56 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 64-fold increase | 35 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 4-fold increase | 59 Participants |
| VLA1553 ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 8-fold increase | 59 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 16-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 64-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 8-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 3 - Day 29: Subjects reaching 4-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 4-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 64-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 16-fold increase | 0 Participants |
| Placebo ≥65 Years | Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline | Visit 5 - Day 180: Subjects reaching 8-fold increase | 0 Participants |
Secondary
Number of Participants With Seroconversion
Seroconversion was defined as CHIKV-specific neutralizing antibody titer of ≥ 20 based on µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects
Time frame: Until Day 180
Population: The Per-Protocol population used for immunogenicity analyses, is based on participants without major protocol deviations that could impact the immune response.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VLA1553 18-64 Years | Number of Participants With Seroconversion | Visit 3 - Day 29 | 205 Participants |
| VLA1553 18-64 Years | Number of Participants With Seroconversion | Visit 5 - Day 180 | 181 Participants |
| Placebo 18-64 Years | Number of Participants With Seroconversion | Visit 5 - Day 180 | 0 Participants |
| Placebo 18-64 Years | Number of Participants With Seroconversion | Visit 3 - Day 29 | 1 Participants |
| VLA1553 ≥65 Years | Number of Participants With Seroconversion | Visit 5 - Day 180 | 57 Participants |
| VLA1553 ≥65 Years | Number of Participants With Seroconversion | Visit 3 - Day 29 | 59 Participants |
| Placebo ≥65 Years | Number of Participants With Seroconversion | Visit 5 - Day 180 | 0 Participants |
| Placebo ≥65 Years | Number of Participants With Seroconversion | Visit 3 - Day 29 | 0 Participants |
Secondary
Number of Participants With Seroprotective CHIKV Antibody Level
Seroprotection rate, based on a surrogate of protection agreed with FDA Seroprotective CHIKV Antibody Level Defined as μPRNT (Micro Plaque Reduction Neutralization Test) for Baseline Negative Subjects
Time frame: Until Day 180
Population: The Per-Protocol population used for immunogenicity analyses, is based on participants without major protocol deviations (PDs) that could impact the immune response.~Counts of participants per time point vary: baseline AND post-line µPRNT result are needed at a given timepoint; results for a specific timepoint were excluded in case of major PD (e.g., major time window deviation resulted in exclusion of a result for a given visit/ time point, results from earlier/ later visits were included)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VLA1553 18-64 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 2 - Day 8 | 2 Participants |
| VLA1553 18-64 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 5 - Day 180 | 178 Participants |
| VLA1553 18-64 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 4 - Day 85 | 189 Participants |
| Placebo 18-64 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 2 - Day 8 | 0 Participants |
| Placebo 18-64 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 5 - Day 180 | 0 Participants |
| Placebo 18-64 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 4 - Day 85 | 0 Participants |
| VLA1553 ≥65 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 4 - Day 85 | 52 Participants |
| VLA1553 ≥65 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 2 - Day 8 | 2 Participants |
| VLA1553 ≥65 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 5 - Day 180 | 55 Participants |
| Placebo ≥65 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 2 - Day 8 | 0 Participants |
| Placebo ≥65 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 5 - Day 180 | 0 Participants |
| Placebo ≥65 Years | Number of Participants With Seroprotective CHIKV Antibody Level | Visit 4 - Day 85 | 0 Participants |
Secondary
Related Adverse Event of Special Interest
Number of Participants with any Related Adverse Event of Special Interest AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: 1. Fever (≥38.0°C \[100.4°F\] measured orally) and 2. Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus \[foot plant\] and edema of the face and extremities), polyadenopathies; and 3. Onset of symptoms 2 to 21 days after vaccination and 4. Duration of event ≥3 days.
Time frame: within 21 days post-vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Related Adverse Event of Special Interest | 9 Participants |
| Placebo 18-64 Years | Related Adverse Event of Special Interest | 1 Participants |
Secondary
Related Adverse Events
Number of Participants with any related Adverse Events
Time frame: until Day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Related Adverse Events | 1575 Participants |
| Placebo 18-64 Years | Related Adverse Events | 322 Participants |
Secondary
Related Serious Adverse Event
Number of Participants with any Related Serious Adverse Events
Time frame: until Day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Related Serious Adverse Event | 2 Participants |
| Placebo 18-64 Years | Related Serious Adverse Event | 0 Participants |
Secondary
Serious Adverse Event
Number of Participants with any Serious Adverse Events
Time frame: until Day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Serious Adverse Event | 46 Participants |
| Placebo 18-64 Years | Serious Adverse Event | 8 Participants |
Secondary
Solicited Injection Site AEs
Number of Participants with solicited injection site reactions
Time frame: within 10 days post-vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VLA1553 18-64 Years | Solicited Injection Site AEs | Any Solicited Injection Site Adverse Event | 463 Participants |
| VLA1553 18-64 Years | Solicited Injection Site AEs | Tenderness | 328 Participants |
| VLA1553 18-64 Years | Solicited Injection Site AEs | Pain | 191 Participants |
| VLA1553 18-64 Years | Solicited Injection Site AEs | Erythema/Redness | 46 Participants |
| VLA1553 18-64 Years | Solicited Injection Site AEs | Induration | 44 Participants |
| VLA1553 18-64 Years | Solicited Injection Site AEs | Swelling | 21 Participants |
| Placebo 18-64 Years | Solicited Injection Site AEs | Induration | 8 Participants |
| Placebo 18-64 Years | Solicited Injection Site AEs | Any Solicited Injection Site Adverse Event | 115 Participants |
| Placebo 18-64 Years | Solicited Injection Site AEs | Erythema/Redness | 15 Participants |
| Placebo 18-64 Years | Solicited Injection Site AEs | Tenderness | 84 Participants |
| Placebo 18-64 Years | Solicited Injection Site AEs | Swelling | 8 Participants |
| Placebo 18-64 Years | Solicited Injection Site AEs | Pain | 38 Participants |
Secondary
Solicited Systemic AEs
Number of Participants with solicited systemic reactions
Time frame: within 10 days post-vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VLA1553 18-64 Years | Solicited Systemic AEs | Fatigue | 879 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Fever | 414 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Headache | 969 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Nausea | 345 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Myalgia | 735 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Rash | 70 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Any Solicited Systemic Adverse Event | 1547 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Vomiting | 58 Participants |
| VLA1553 18-64 Years | Solicited Systemic AEs | Arthralgia | 520 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Vomiting | 10 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Fatigue | 130 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Any Solicited Systemic Adverse Event | 278 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Myalgia | 76 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Arthralgia | 50 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Fever | 8 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Nausea | 58 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Rash | 5 Participants |
| Placebo 18-64 Years | Solicited Systemic AEs | Headache | 151 Participants |
Secondary
Unsolicited AEs
Number of Participants with Unsolicited Adverse Events
Time frame: Until Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VLA1553 18-64 Years | Unsolicited AEs | 687 Participants |
| Placebo 18-64 Years | Unsolicited AEs | 138 Participants |