Trial Outcomes & Findings for Pivotal Study to Evaluate Safety and Immunogenicity of a Live-Attenuated Chikungunya Virus Vaccine Candidate in Adults (NCT NCT04546724)

Last Updated: 2023-06-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4128 participants

Primary outcome timeframe

on Day 29 after single vaccination

Results posted on

2023-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	VLA1553 VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Overall Study STARTED	3082	1033
Overall Study COMPLETED	2724	920
Overall Study NOT COMPLETED	358	113

Reasons for withdrawal

Reasons for withdrawal
Measure	VLA1553 VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Overall Study Withdrawal by Subject	145	41
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	186	63
Overall Study Physician Decision	8	2
Overall Study Death	2	1
Overall Study subject has been out of town	1	0
Overall Study subject is incarcerated	2	0
Overall Study subject is relocating	12	4
Overall Study Subject in another study	1	1

Baseline Characteristics

Pivotal Study to Evaluate Safety and Immunogenicity of a Live-Attenuated Chikungunya Virus Vaccine Candidate in Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VLA1553 n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	Total n=4115 Participants Total of all reporting groups
Age, Continuous	45.1 years STANDARD_DEVIATION 15.44 • n=5 Participants	45.0 years STANDARD_DEVIATION 15.59 • n=7 Participants	45.0 years STANDARD_DEVIATION 15.47 • n=5 Participants
Sex: Female, Male Female	1682 Participants n=5 Participants	569 Participants n=7 Participants	2251 Participants n=5 Participants
Sex: Female, Male Male	1400 Participants n=5 Participants	464 Participants n=7 Participants	1864 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	27 Participants n=5 Participants	5 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Asian	51 Participants n=5 Participants	17 Participants n=7 Participants	68 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	451 Participants n=5 Participants	122 Participants n=7 Participants	573 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized White	2456 Participants n=5 Participants	853 Participants n=7 Participants	3309 Participants n=5 Participants
Race/Ethnicity, Customized Other	84 Participants n=5 Participants	31 Participants n=7 Participants	115 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=207 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=73 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years n=59 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years n=23 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination	204 Participants	0 Participants	59 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

CHIKV-specific Neutralizing Antibody Titers on Day 8, and Day 29 Postvaccination as Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) Assay

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=207 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=73 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years n=59 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years n=23 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
CHIKV-specific Neutralizing Antibody Titers Visit 2 - Day 8	13.6 Antibody Titers Interval 12.22 to 15.23	10.2 Antibody Titers Interval 9.92 to 10.5	13.4 Antibody Titers Interval 11.05 to 16.31	10.0 Antibody Titers Interval 10.0 to 10.0
CHIKV-specific Neutralizing Antibody Titers Visit 3 - Day 29	3273.7 Antibody Titers Interval 2860.93 to 3746.04	10.1 Antibody Titers Interval 9.89 to 10.33	3688.8 Antibody Titers Interval 2938.94 to 4630.1	10.0 Antibody Titers Interval 10.0 to 10.0
CHIKV-specific Neutralizing Antibody Titers Visit 4 - Day 85	1068.7 Antibody Titers Interval 934.77 to 1221.82	10.0 Antibody Titers Interval 10.0 to 10.0	1140.9 Antibody Titers Interval 942.97 to 1380.31	10.7 Antibody Titers Interval 9.71 to 11.78
CHIKV-specific Neutralizing Antibody Titers Visit 5 - Day 180	755.1 Antibody Titers Interval 656.01 to 869.16	10.0 Antibody Titers Interval 10.0 to 10.0	742.8 Antibody Titers Interval 578.36 to 954.0	10.0 Antibody Titers Interval 10.0 to 10.0

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=207 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=73 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years n=59 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years n=23 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Number of Participants With Seroprotective CHIKV Antibody Level Visit 2 - Day 8	2 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Seroprotective CHIKV Antibody Level Visit 4 - Day 85	189 Participants	0 Participants	52 Participants	0 Participants
Number of Participants With Seroprotective CHIKV Antibody Level Visit 5 - Day 180	178 Participants	0 Participants	55 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Seroconversion was defined as CHIKV-specific neutralizing antibody titer of ≥ 20 based on µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=207 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=73 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years n=59 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years n=23 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Number of Participants With Seroconversion Visit 3 - Day 29	205 Participants	1 Participants	59 Participants	0 Participants
Number of Participants With Seroconversion Visit 5 - Day 180	181 Participants	0 Participants	57 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=207 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=73 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years n=59 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years n=23 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline Visit 3 - Day 29	460.27 fold increase Standard Deviation 384.052	1.02 fold increase Standard Deviation 0.140	507.70 fold increase Standard Deviation 412.467	1.00 fold increase Standard Deviation 0.000
Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline Visit 5 - Day 180	108.81 fold increase Standard Deviation 97.238	1.00 fold increase Standard Deviation 0.000	102.09 fold increase Standard Deviation 79.433	1.00 fold increase Standard Deviation 0.000

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=207 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=73 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years n=59 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years n=23 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
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	0 Participants	59 Participants	0 Participants
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	0 Participants	59 Participants	0 Participants
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	0 Participants	59 Participants	0 Participants
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	0 Participants	57 Participants	0 Participants
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	0 Participants	57 Participants	0 Participants
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	0 Participants	56 Participants	0 Participants
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	0 Participants	55 Participants	0 Participants
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	0 Participants	35 Participants	0 Participants

SECONDARY outcome

Timeframe: Until Day 29

Number of Participants with Unsolicited Adverse Events

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Unsolicited AEs	687 Participants	138 Participants	—	—

SECONDARY outcome

Timeframe: within 10 days post-vaccination

Number of Participants with solicited injection site reactions

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Solicited Injection Site AEs Any Solicited Injection Site Adverse Event	463 Participants	115 Participants	—	—
Solicited Injection Site AEs Tenderness	328 Participants	84 Participants	—	—
Solicited Injection Site AEs Pain	191 Participants	38 Participants	—	—
Solicited Injection Site AEs Erythema/Redness	46 Participants	15 Participants	—	—
Solicited Injection Site AEs Induration	44 Participants	8 Participants	—	—
Solicited Injection Site AEs Swelling	21 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: within 10 days post-vaccination

Number of Participants with solicited systemic reactions

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Solicited Systemic AEs Vomiting	58 Participants	10 Participants	—	—
Solicited Systemic AEs Any Solicited Systemic Adverse Event	1547 Participants	278 Participants	—	—
Solicited Systemic AEs Headache	969 Participants	151 Participants	—	—
Solicited Systemic AEs Fatigue	879 Participants	130 Participants	—	—
Solicited Systemic AEs Myalgia	735 Participants	76 Participants	—	—
Solicited Systemic AEs Arthralgia	520 Participants	50 Participants	—	—
Solicited Systemic AEs Fever	414 Participants	8 Participants	—	—
Solicited Systemic AEs Nausea	345 Participants	58 Participants	—	—
Solicited Systemic AEs Rash	70 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: until Day 180

Number of Participants with any Adverse Events

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Adverse Events Mild	1287 Participants	336 Participants	—	—
Adverse Events Moderate	532 Participants	112 Participants	—	—
Adverse Events Severe	104 Participants	14 Participants	—	—

SECONDARY outcome

Timeframe: until Day 180

Number of Participants with any related Adverse Events

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Related Adverse Events	1575 Participants	322 Participants	—	—

SECONDARY outcome

Timeframe: until Day 180

Number of Participants with any Serious Adverse Events

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Serious Adverse Event	46 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: until Day 180

Number of Participants with any Related Serious Adverse Events

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Related Serious Adverse Event	2 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Adverse Event of Special Interest	10 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	VLA1553 18-64 Years n=3082 Participants VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo 18-64 Years n=1033 Participants Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553 ≥65 Years VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo ≥65 Years Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Related Adverse Event of Special Interest	9 Participants	1 Participants	—	—

Adverse Events

VLA1553

Serious events: 46 serious events

Other events: 1721 other events

Deaths: 2 deaths

Placebo

Serious events: 8 serious events

Other events: 373 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Strategy Manager

Valn

Phone: +43 1 206 20

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	VLA1553 n=3082 participants at risk VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo n=1033 participants at risk Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Nervous system disorders Headache	32.0% 986/3082 • Number of events 1028 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	15.5% 160/1033 • Number of events 178 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
General disorders Fatigue	28.7% 886/3082 • Number of events 893 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	13.3% 137/1033 • Number of events 139 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Musculoskeletal and connective tissue disorders Myalgia	24.3% 750/3082 • Number of events 758 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	7.9% 82/1033 • Number of events 84 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Musculoskeletal and connective tissue disorders Arthralgia	18.0% 554/3082 • Number of events 589 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	6.1% 63/1033 • Number of events 70 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
General disorders Injection site pain	13.4% 413/3082 • Number of events 519 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	9.8% 101/1033 • Number of events 122 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
General disorders Pyrexia	13.9% 427/3082 • Number of events 429 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	1.3% 13/1033 • Number of events 13 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Gastrointestinal disorders Nausea	11.6% 359/3082 • Number of events 364 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	6.1% 63/1033 • Number of events 64 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Skin and subcutaneous tissue disorders Rash	2.7% 82/3082 • Number of events 86 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	1.2% 12/1033 • Number of events 12 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Infections and infestations COVID-19	1.9% 59/3082 • Number of events 70 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	2.1% 22/1033 • Number of events 23 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Gastrointestinal disorders Vomiting	2.1% 66/3082 • Number of events 67 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	1.4% 14/1033 • Number of events 14 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
General disorders Chills	1.9% 59/3082 • Number of events 60 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	0.29% 3/1033 • Number of events 3 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
General disorders Injection site erythema	1.5% 47/3082 • Number of events 47 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	1.5% 15/1033 • Number of events 15 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
General disorders Injection site induration	1.4% 44/3082 • Number of events 44 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	0.77% 8/1033 • Number of events 8 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Musculoskeletal and connective tissue disorders Back pain	1.4% 44/3082 • Number of events 46 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	0.68% 7/1033 • Number of events 7 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Gastrointestinal disorders Diarrhoea	1.5% 46/3082 • Number of events 46 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	0.39% 4/1033 • Number of events 4 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Renal and urinary disorders Urinary tract infection	1.1% 33/3082 • Number of events 36 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	0.58% 6/1033 • Number of events 6 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.
Blood and lymphatic system disorders Neutropenia	1.1% 34/3082 • Number of events 34 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.	0.10% 1/1033 • Number of events 1 • Day 180 Solicited AEs are collected by systematic assessment through subject eDiaries (within 10 days post-vaccination):injection site AEs (pain, tenderness, induration, swelling, erythema/redness) or systemic AEs (headache, myalgia, arthralgia, fever, vomiting, nausea, rash, fatigue). Unsolicited AEs, and SAEs are collected by non-systematic assessment up to Day 180. AESI is defined as symptoms suggestive of CHIKV infection up to 21 days after vaccination and collected by systematic assessment.