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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
4,128
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
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
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
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
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
Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline
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Accelerated Enrollment Solutions (AES)
Chandler, Arizona, United States
Accelerated Enrollment Solutions (AES)
Phoenix, Arizona, United States
Alliance for Multispecialty Research (AMR)
Tempe, Arizona, United States
ELITE Research Network (ELITE)
Little Rock, Arkansas, United States
Velocity Clinical Research, Chula Vista
Chula Vista, California, United States
Accelerated Enrollment Solutions (AES)
San Diego, California, United States
Accel Research Sites - DeLand
DeLand, Florida, United States
ELITE Research Network (ELITE)
Hallandale, Florida, United States
Meridien Research - Maitland
Maitland, Florida, United States
Accelerated Enrollment Solutions (AES)
Melbourne, Florida, United States
...and 34 more locations
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
Unsolicited AEs
Number of Participants with Unsolicited Adverse Events
Time frame: Until Day 29
Solicited Injection Site AEs
Number of Participants with solicited injection site reactions
Time frame: within 10 days post-vaccination
Solicited Systemic AEs
Number of Participants with solicited systemic reactions
Time frame: within 10 days post-vaccination
Adverse Events
Number of Participants with any Adverse Events
Time frame: until Day 180
Related Adverse Events
Number of Participants with any related Adverse Events
Time frame: until Day 180
Serious Adverse Event
Number of Participants with any Serious Adverse Events
Time frame: until Day 180
Related Serious Adverse Event
Number of Participants with any Related Serious Adverse Events
Time frame: until Day 180
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
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