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)
4,124
44
2
12.9
93.7
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
  • 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)

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
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
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.

Results Point of Contact

Name/Title Clinical Strategy Manager
Organization Valn
Phone +43 1 206 20 ext 0
Email office@valneva.com
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