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

• Sponsor: Valneva Austria GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04546724
• Collaborator: (none)
• Enrollment: 4,124
• Locations: 44
• Arms: 2
• Actual Duration (Months): 12.9
• Patients Per Site: 93.7
• Patients Per Site Per Month: 7.3

Study Details

Study Description

Brief Summary

This is 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 will be administered as single immunization on Day 1. Overall, approximately 4,060 male and female subjects aged 18 years and above will be enrolled into the study.

Condition or Disease	Intervention/Treatment	Phase
Chikungunya Virus Infection	Biological: VLA1553; Biological: Placebo	Phase 3

Detailed Description

This is a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study comprising approximately 4,060 subjects aged 18 years or above randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The final dose of lyophilized VLA1553 or placebo will be administered as a single intramuscular immunization. Subjects in this study will be stratified into two age strata of 18 to 64 years and 65 years of age or above. The primary objective of the study is to evaluate the immunogenicity and safety of the final dose of VLA1553 28 days following the single immunization. Immunogenicity evaluations in the immunogenicity subset will include 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. Safety data collection and immunogenicity will continue to be assessed until Month 6

The first enrolled and randomized approximately 500 subjects will comprise the immunogenicity subset.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Randomized, Placebo-Controlled, Double-Blinded Pivotal Study To Evaluate Safety And Immunogenicity Of A Live-Attenuated Chikungunya Virus Vaccine Candidate In Adults Aged 18 Years And Above
• Actual Study Start Date: Sep 17, 2020
• Actual Primary Completion Date: May 19, 2021
• Actual Study Completion Date: Oct 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: VLA1553 Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Biological: VLA1553; Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose
Placebo Comparator: Placebo Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	Biological: Placebo; Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo

Outcome Measures

Primary Outcome Measures

1. 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 is 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 Outcome Measures

1. CHIKV-specific Neutralizing Antibody Titers [Until Day 29]

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

2. Number of Participants With Seroprotective CHIKV Antibody Level [Until Day 29]

   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

3. Number of Participants With Seroconversion [Until Day 29]

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

4. Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline [until Day 29]

   Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline calculation of fold change: Day 8/ Baseline and Day 29/ Baseline

5. Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline [until Day 29]

   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

6. Unsolicited AEs [Until Day 29]

   Number of Participants with Unsolicited Adverse Events

7. Solicited Injection Site AEs [within 10 days post-vaccination]

   Number of Participants with solicited injection site reactions

8. Solicited Systemic AEs [within 10 days post-vaccination]

   Number of Participants with solicited systemic reactions

9. Adverse Events [until Day 29]

   Number of Participants with any Adverse Events

10. Related Adverse Events [until Day 29]

    Number of Participants with any related Adverse Events

11. Serious Adverse Event [until Day 29]

    Number of Participants with any Serious Adverse Events

12. Related Serious Adverse Event [until Day 29]

    Number of Participants with any Related Serious Adverse Events

13. 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 will receive particular consideration: Fever (≥38.0°C [100.4°F] measured orally) and 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 Onset of symptoms 2 to 21 days after vaccination and Duration of event ≥3 days.

14. 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 will receive particular consideration: Fever (≥38.0°C [100.4°F] measured orally) and 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 Onset of symptoms 2 to 21 days after vaccination and Duration of event ≥3 days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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:

5. practiced an adequate method of contraception during 30 days before screening

6. negative serum or urine pregnancy test at screening

7. agrees to employ adequate birth control measures for the first three months post-vaccination (i.e. until Day 85).

Main Exclusion Criteria:

1. CHIKV infection in the past, including suspected CHIKV infection; is taking medication or other treatment for unresolved symptoms attributed to a previous CHIKV infection; or has participated in a clinical study involving an investigational CHIKV vaccine

2. acute or recent infection

3. Subject tests 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 plans 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 has acute or progressive, unstable or uncontrolled clinical conditions that pose 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 has been surgical excision or treatment more than 5 years ago that is considered to have achieved a cure, the subject may 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 plans to donate blood or use 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, may compromise the subjects well-being, might 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Accelerated Enrollment Solutions (AES)	Chandler	Arizona	United States	85224
2	Accelerated Enrollment Solutions (AES)	Phoenix	Arizona	United States	85020
3	Alliance for Multispecialty Research (AMR)	Tempe	Arizona	United States	85283
4	ELITE Research Network (ELITE)	Little Rock	Arkansas	United States	72204
5	Velocity Clinical Research, Chula Vista	Chula Vista	California	United States	91911
6	Accelerated Enrollment Solutions (AES)	San Diego	California	United States	92108
7	Accel Research Sites - DeLand	DeLand	Florida	United States	32720
8	ELITE Research Network (ELITE)	Hallandale Beach	Florida	United States	33009
9	Meridien Research - Maitland	Maitland	Florida	United States	32751
10	Accelerated Enrollment Solutions (AES)	Melbourne	Florida	United States	32934
11	Suncoast Research Group, LLC	Miami	Florida	United States	33135
12	ELITE Research Network (ELITE)	North Miami Beach	Florida	United States	33135
13	Jacksonville Center for Clinical Research, LTD dba St. Johns Center for Clinical Research	Ponte Vedra	Florida	United States	32081
14	Synexus - The Villages	The Villages	Florida	United States	32162
15	ELITE Research Network (ELITE)	Meridian	Idaho	United States	83642
16	Accelerated Enrollment Solutions (AES)	Chicago	Illinois	United States	60602
17	Accelerated Enrollment Solutions (AES)	Peoria	Illinois	United States	61614
18	Alliance for Multispecialty Research (AMR)	El Dorado	Kansas	United States	67042
19	Alliance for Multispecialty Research (AMR)	Newton	Kansas	United States	67114
20	Alliance for Multispecialty Research (AMR)	Wichita	Kansas	United States	67207
21	Alliance for Multispecialty Research (AMR)	Lexington	Kentucky	United States	40509
22	AMR - New Orleans - Center for Clinical Research	New Orleans	Louisiana	United States	70119
23	Alliance for Multispecialty Research (AMR)	Kansas City	Missouri	United States	64114
24	Meridian Clinical Research - Grand Island	Grand Island	Nebraska	United States	68803
25	Platinum Research Network (Platinum)	Omaha	Nebraska	United States	68134
26	Accelerated Enrollment Solutions (AES)	Omaha	Nebraska	United States	68144
27	Alliance for Multispecialty Research (AMR)	Las Vegas	Nevada	United States	89119
28	Meridian Clinical Research	Endwell	New York	United States	13760
29	Rochester Clinical Research	Rochester	New York	United States	14609
30	Lucas Research	Morehead City	North Carolina	United States	28557
31	ELITE Research Network (ELITE)	Wilmington	North Carolina	United States	28403
32	Accelerated Enrollment Solutions (AES)	Cincinnati	Ohio	United States	45236
33	ELITE Research Network (ELITE)	Oklahoma City	Oklahoma	United States	73112
34	Velocity Clinical Research - Medford	Medford	Oregon	United States	97504
35	Synexus - Anderson	Anderson	South Carolina	United States	29621
36	Vitalink Research - Anderson	Anderson	South Carolina	United States	29621
37	Alliance for Multispecialty Research (AMR)	Knoxville	Tennessee	United States	37920
38	Tekton Research - Beaumont	Beaumont	Texas	United States	77706
39	PanAmerican Clinical Research - US Headquarter	Brownsville	Texas	United States	78521
40	Velocity Clinical Research - Austin	Cedar Park	Texas	United States	78613
41	Research Your Health, LLC	Plano	Texas	United States	75093
42	ELITE Research Network (ELITE)	Tomball	Texas	United States	77375
43	ELITE Research Network (ELITE)	West Jordan	Utah	United States	84088
44	Alliance for Multispecialty Research (AMR)	Norfolk	Virginia	United States	23507

Sponsors and Collaborators

• Valneva Austria GmbH

Investigators

• Study Chair: Valneva Clinical Development, Valneva Austria GmbH

Study Documents (Full-Text)

• Study Protocol - Mar 23, 2021
• Statistical Analysis Plan - Jan 14, 2022

More Information

Publications

None provided.

• Responsible Party: Valneva Austria GmbH
• ClinicalTrials.gov Identifier: NCT04546724
• Other Study ID Numbers: VLA1553-301
• First Posted: Sep 14, 2020
• Last Update Posted: Jul 29, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Valneva Austria GmbH: VLA1553; Chikungunya Virus Infection; CHIKV; Live-attenuated Chikungunya virus vaccine
• Additional relevant MeSH terms: Virus Diseases; Chikungunya Fever

Study Results

Participant Flow

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Period Title: Overall Study
STARTED	3082	1033
COMPLETED	2959	998
NOT COMPLETED	123	35

Baseline Characteristics

Arm/Group Title	VLA1553	Placebo	Total
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	Total of all reporting groups
Overall Participants	3082	1033	4115
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.1 (15.44)	45.0 (15.59)	45.0 (15.47)
Sex: Female, Male (Count of Participants)
Female	1681 54.5%	570 55.2%	2251 54.7%
Male	1401 45.5%	463 44.8%	1864 45.3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	27 0.9%	5 0.5%	32 0.8%
Asian	51 1.7%	17 1.6%	68 1.7%
Black or African American	451 14.6%	122 11.8%	573 13.9%
Native Hawaiian or other Pacific Islander	13 0.4%	5 0.5%	18 0.4%
White	2456 79.7%	853 82.6%	3309 80.4%
Other	84 2.7%	31 3%	115 2.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination
Description	Seroprotection rate, based on a surrogate of protection agreed with FDA Assay used for analysis is 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553 18-64 Years	Placebo 18-64 Years	VLA1553 ≥65 Years	Placebo ≥65 Years
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	209	73	59	23
Count of Participants [Participants]	206 6.7%	0 0%	58 1.4%	0 NaN

2. Secondary Outcome

Title	CHIKV-specific Neutralizing Antibody Titers
Description	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 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553 18-64 Years	Placebo 18-64 Years	VLA1553 ≥65 Years	Placebo ≥65 Years
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	209	73	59	23
Visit 2 - Day 8	13.6	10.2	13.2	10.0
Visit 3 - Day 29	3244.0	10.1	3361.6	10.0

3. Secondary Outcome

Title	Number of Participants With Seroprotective CHIKV Antibody Level
Description	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 29

Outcome Measure Data

Analysis Population Description

The Per-Protocol population used for immunogenicity analyses, is based on participants who have available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response.

Arm/Group Title	VLA1553 18-64 Years	Placebo 18-64 Years	VLA1553 ≥65 Years	Placebo ≥65 Years
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	209	73	59	23
Visit 2 - Day 8	2 0.1%	0 0%	2 0%	0 NaN
Visit 3 - Day 29	206 6.7%	0 0%	58 1.4%	0 NaN

4. Secondary Outcome

Title	Number of Participants With Seroconversion
Description	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 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553 18-64 Years	Placebo 18-64 Years	VLA1553 ≥65 Years	Placebo ≥65 Years
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	209	73	59	23
Count of Participants [Participants]	207 6.7%	1 0.1%	58 1.4%	0 NaN

5. Secondary Outcome

Title	Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline
Description	Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline calculation of fold change: Day 8/ Baseline and Day 29/ Baseline
Time Frame	until Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553 18-64 Years	Placebo 18-64 Years	VLA1553 ≥65 Years	Placebo ≥65 Years
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	209	73	59	23
Visit 2 - Day 8	4.36 (30.207)	1.03 (0.176)	2.04 (3.308)	1.00 (0.000)
Visit 3 - Day 29	457.44 (383.427)	1.02 (0.140)	503.65 (416.298)	1.00 (0.000)

6. Secondary Outcome

Title	Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline
Description	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 29

Outcome Measure Data

Analysis Population Description

The Per-Protocol population used for immunogenicity analyses, is based on participants who have available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response.

Arm/Group Title	VLA1553 18-64 Years	Placebo 18-64 Years	VLA1553 ≥65 Years	Placebo ≥65 Years
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	209	73	59	23
Visit 2 - Day 8: subjects reaching 4-fold increase	17 0.6%	0 0%	5 0.1%	0 NaN
Visit 2 - Day 8 subjects reaching 8-fold increase	7 0.2%	0 0%	3 0.1%	0 NaN
Visit 2 - Day 8 subjects reaching 16-fold increase	2 0.1%	0 0%	2 0%	0 NaN
Visit 2 - Day 8: subjects reaching 64-fold increase	2 0.1%	0 0%	0 0%	0 NaN
Visit 3 - Day 29: Subjects reaching 4-fold increase	207 6.7%	0 0%	58 1.4%	0 NaN
Visit 3 - Day 29: Subjects reaching 8-fold increase	207 6.7%	0 0%	58 1.4%	0 NaN
Visit 3 - Day 29: Subjects reaching 16-fold increase	206 6.7%	0 0%	58 1.4%	0 NaN
Visit 3 - Day 29: Subjects reaching 64-fold increase	201 6.5%	0 0%	56 1.4%	0 NaN

7. Secondary Outcome

Title	Unsolicited AEs
Description	Number of Participants with Unsolicited Adverse Events
Time Frame	Until Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Count of Participants [Participants]	639 20.7%	126 12.2%

8. Secondary Outcome

Title	Solicited Injection Site AEs
Description	Number of Participants with solicited injection site reactions
Time Frame	within 10 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Any Solicited Injection Site Adverse Event	456 14.8%	113 10.9%
Tenderness	320 10.4%	83 8%
Pain	189 6.1%	37 3.6%
Erythema/Redness	44 1.4%	14 1.4%
Induration	43 1.4%	8 0.8%
Swelling	22 0.7%	9 0.9%

9. Secondary Outcome

Title	Solicited Systemic AEs
Description	Number of Participants with solicited systemic reactions
Time Frame	within 10 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Any Solicited Systemic Adverse Event	1529 49.6%	273 26.4%
Headache	951 30.9%	148 14.3%
Fatigue	858 27.8%	128 12.4%
Myalgia	718 23.3%	71 6.9%
Arthralgia	490 15.9%	49 4.7%
Fever	405 13.1%	7 0.7%
Nausea	335 10.9%	56 5.4%
Rash	67 2.2%	6 0.6%
Vomiting	58 1.9%	10 1%

10. Secondary Outcome

Title	Adverse Events
Description	Number of Participants with any Adverse Events
Time Frame	until Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Mild	1287 41.8%	314 30.4%
Moderate	430 14%	69 6.7%
Severe	65 2.1%	7 0.7%

11. Secondary Outcome

Title	Related Adverse Events
Description	Number of Participants with any related Adverse Events
Time Frame	until Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Count of Participants [Participants]	1558 50.6%	311 30.1%

12. Secondary Outcome

Title	Serious Adverse Event
Description	Number of Participants with any Serious Adverse Events
Time Frame	until Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Count of Participants [Participants]	14 0.5%	4 0.4%

13. Secondary Outcome

Title	Related Serious Adverse Event
Description	Number of Participants with any Related Serious Adverse Events
Time Frame	until Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Count of Participants [Participants]	2 0.1%	0 0%

14. Secondary Outcome

Title	Adverse Event of Special Interest
Description	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 will receive particular consideration: Fever (≥38.0°C [100.4°F] measured orally) and 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 Onset of symptoms 2 to 21 days after vaccination and Duration of event ≥3 days.
Time Frame	within 21 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Count of Participants [Participants]	10 0.3%	1 0.1%

15. Secondary Outcome

Title	Related Adverse Event of Special Interest
Description	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 will receive particular consideration: Fever (≥38.0°C [100.4°F] measured orally) and 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 Onset of symptoms 2 to 21 days after vaccination and Duration of event ≥3 days.
Time Frame	within 21 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VLA1553	Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose	Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
Measure Participants	3082	1033
Count of Participants [Participants]	9 0.3%	1 0.1%

Adverse Events

Time Frame	29 Days
Adverse Event Reporting Description	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.
Arm/Group Title	VLA1553		Placebo
Arm/Group Description	VLA1553: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose		Placebo: Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo
All Cause Mortality
	VLA1553		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3082 (0%)		0/1033 (0%)
Serious Adverse Events
	VLA1553		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/3082 (0.5%)		4/1033 (0.4%)
Cardiac disorders
Atrial fibrillation	1/3082 (0%)	1	0/1033 (0%)	0
Endocrine disorders
Inappropriate antidiuretic hormone secretion	1/3082 (0%)	1	0/1033 (0%)	0
Gastrointestinal disorders
Gastrointestinal haemorrage	0/3082 (0%)	0	1/1033 (0.1%)	1
Hepatobiliary disorders
Cholecystitis	1/3082 (0%)	1	0/1033 (0%)	0
Infections and infestations
Appendicitis	1/3082 (0%)	1	0/1033 (0%)	0
COVID-19	0/3082 (0%)	0	1/1033 (0.1%)	1
Complicated appendicitis	1/3082 (0%)	1	0/1033 (0%)	0
Pneumonia	1/3082 (0%)	1	0/1033 (0%)	0
Pyelonephritis	1/3082 (0%)	1	0/1033 (0%)	0
Injury, poisoning and procedural complications
Alcohol poisoning	1/3082 (0%)	1	0/1033 (0%)	0
Ankle fracture	1/3082 (0%)	1	0/1033 (0%)	0
Fall	1/3082 (0%)	1	0/1033 (0%)	0
Fibula fracture	1/3082 (0%)	1	0/1033 (0%)	0
Overdose	1/3082 (0%)	1	0/1033 (0%)	0
Tendon rupture	1/3082 (0%)	1	0/1033 (0%)	0
Tibia fracture	1/3082 (0%)	1	0/1033 (0%)	0
Metabolism and nutrition disorders
Glucose tolerance impaired	1/3082 (0%)	1	0/1033 (0%)	0
Hypokalaemia	1/3082 (0%)	1	0/1033 (0%)	0
Musculoskeletal and connective tissue disorders
Mylgia	1/3082 (0%)	1	0/1033 (0%)	0
Nervous system disorders
Cerebellar haemorrhage	0/3082 (0%)	0	1/1033 (0.1%)	1
Psychiatric disorders
Suicidal ideation	2/3082 (0.1%)	2	1/1033 (0.1%)	1
Anxiety	0/3082 (0%)	0	1/1033 (0.1%)	1
Bipolar disorder	1/3082 (0%)	1	0/1033 (0%)	0
Depression	1/3082 (0%)	1	0/1033 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/3082 (0%)	1	0/1033 (0%)	0
Hydronephrosis	1/3082 (0%)	1	0/1033 (0%)	0
Nephrolithiasis	1/3082 (0%)	1	0/1033 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/3082 (0%)	1	0/1033 (0%)	0
Other (Not Including Serious) Adverse Events
	VLA1553		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1649/3082 (53.5%)		342/1033 (33.1%)
Blood and lymphatic system disorders
Neutropenia	33/3082 (1.1%)	33	1/1033 (0.1%)	1
Gastrointestinal disorders
Nausea	339/3082 (11%)	364	59/1033 (5.7%)	64
Vomiting	61/3082 (2%)	62	12/1033 (1.2%)	12
Diarrhoea	39/3082 (1.3%)	39	3/1033 (0.3%)	3
General disorders
Fatigue	862/3082 (28%)	959	130/1033 (12.6%)	140
Injection site pain	407/3082 (13.2%)	541	100/1033 (9.7%)	124
Pyrexia	415/3082 (13.5%)	442	8/1033 (0.8%)	8
Injection site erythema	44/3082 (1.4%)	44	14/1033 (1.4%)	14
Chills	53/3082 (1.7%)	53	2/1033 (0.2%)	2
Musculoskeletal and connective tissue disorders
Myalgia	726/3082 (23.6%)	787	73/1033 (7.1%)	84
Arthralgia	512/3082 (16.6%)	563	53/1033 (5.1%)	62
Induration	43/3082 (1.4%)	44	8/1033 (0.8%)	8
Back Pain	34/3082 (1.1%)	36	6/1033 (0.6%)	6
Nervous system disorders
Headache	961/3082 (31.2%)	1115	151/1033 (14.6%)	177
Skin and subcutaneous tissue disorders
Rash	70/3082 (2.3%)	78	9/1033 (0.9%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.