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

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

This was a prospective, randomized, double-blinded, multicenter, pivotal clinical study evaluating the final dose of VLA1553 (1 x10E4 TCID50 per dose) in comparison to a placebo control. The final dose of VLA1553 or control was administered as single immunization on Day 1. Overall, 4.128 male and female subjects aged 18 years and above were randomized into the study.

Study Overview

• Status: Completed
• Conditions: Chikungunya Virus Infection
• Intervention / Treatment: Biological: VLA1553; Biological: Placebo

Detailed Description

This was a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study and 4.128 participants aged 18 years or above were randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The final dose of lyophilized VLA1553 or placebo was administered as a single intramuscular immunization. Subjects in this study were stratified into two age strata of 18 to 64 years and 65 years of age or above. The primary objective of the study was to evaluate the immunogenicity and safety of the final dose of VLA1553 28 days following the single immunization. Immunogenicity evaluations in the immunogenicity subset included the proportion of subjects with seroprotective neutralizing CHIKV antibody titers above a surrogate threshold indicative of protection. The surrogate of protection reasonably likely to predict clinical benefit has been established in non-human primate passive transfer studies using human sera from the Phase 1 study and was supported by sero-epidemiological studies. Safety data collection and immunogenicity were assessed until Month 6.

The first enrolled and randomized 501 subjects comprised the immunogenicity subset.

• Study Type: Interventional
• Enrollment (Actual): 4128
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Accelerated Enrollment Solutions (AES)
    • Phoenix, Arizona, United States, 85020
      • Accelerated Enrollment Solutions (AES)
    • Tempe, Arizona, United States, 85283
      • Alliance for Multispecialty research (AMR)
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • ELITE Research Network (ELITE)
  • California
    • Chula Vista, California, United States, 91911
      • Velocity Clinical Research, Chula Vista
    • San Diego, California, United States, 92108
      • Accelerated Enrollment Solutions (AES)
  • Florida
    • DeLand, Florida, United States, 32720
      • Accel Research Sites - DeLand
    • Hallandale Beach, Florida, United States, 33009
      • ELITE Research Network (ELITE)
    • Maitland, Florida, United States, 32751
      • Meridien Research - Maitland
    • Melbourne, Florida, United States, 32934
      • Accelerated Enrollment Solutions (AES)
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • North Miami Beach, Florida, United States, 33135
      • ELITE Research Network (ELITE)
    • Ponte Vedra, Florida, United States, 32081
      • Jacksonville Center for Clinical Research, LTD dba St. Johns Center for Clinical Research
    • The Villages, Florida, United States, 32162
      • Synexus - The Villages
  • Idaho
    • Meridian, Idaho, United States, 83642
      • ELITE Research Network (ELITE)
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Accelerated Enrollment Solutions (AES)
    • Peoria, Illinois, United States, 61614
      • Accelerated Enrollment Solutions (AES)
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • Alliance for Multispecialty research (AMR)
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty research (AMR)
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty research (AMR)
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance for Multispecialty research (AMR)
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • AMR - New Orleans - Center for Clinical Research
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty research (AMR)
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Meridian Clinical Research - Grand Island
    • Omaha, Nebraska, United States, 68134
      • Platinum Research Network (Platinum)
    • Omaha, Nebraska, United States, 68144
      • Accelerated Enrollment Solutions (AES)
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Alliance for Multispecialty research (AMR)
  • New York
    • Endwell, New York, United States, 13760
      • Meridian Clinical Research
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
    • Wilmington, North Carolina, United States, 28403
      • ELITE Research Network (ELITE)
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Accelerated Enrollment Solutions (AES)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • ELITE Research Network (ELITE)
  • Oregon
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Research - Medford
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Vitalink Research - Anderson
    • Anderson, South Carolina, United States, 29621
      • Synexus - Anderson
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty research (AMR)
  • Texas
    • Beaumont, Texas, United States, 77706
      • Tekton Research - Beaumont
    • Brownsville, Texas, United States, 78521
      • PanAmerican Clinical Research - US Headquarter
    • Cedar Park, Texas, United States, 78613
      • Velocity Clinical Research - Austin
    • Plano, Texas, United States, 75093
      • Research Your Health, LLC
    • Tomball, Texas, United States, 77375
      • ELITE Research Network (ELITE)
  • Utah
    • West Jordan, Utah, United States, 84088
      • ELITE Research Network (ELITE)
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Alliance for Multispecialty research (AMR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 18 years of age or above on the Day of screening
2. able to provide informed consent
3. generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests

4. for women of childbearing potential:

   1. practiced an adequate method of contraception during 30 days before screening
   2. negative serum or urine pregnancy test at screening
   3. agreed to employ adequate birth control measures for the first three months post-vaccination.

Main Exclusion Criteria:

1. CHIKV infection in the past, including suspected CHIKV infection; was taking medication or other treatment for unresolved symptoms attributed to a previous CHIKV infection; or had participated in a clinical study involving an investigational CHIKV vaccine
2. acute or recent infection
3. Subject tested positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);
4. live virus vaccine within 28 days or inactivated vaccine within 14 days prior to vaccination in this study or planned to receive a vaccine within 28 days or 14 days after vaccination, respectively
5. abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator which pose a risk for participation in the study
6. medical history of or currently had acute or progressive, unstable or uncontrolled clinical conditions that posed a risk for participation in the study
7. history of immune-mediated or clinically relevant arthritis / arthralgia
8. history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there had been surgical excision or treatment more than 5 years ago that was considered to have achieved a cure, the subject could be enrolled.
9. known or suspected defect of the immune system, such as subjects with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno-suppressive therapy within 4 weeks prior to vaccination.
10. history of any vaccine related contraindicating event (e.g., anaphylaxis, allergy to components of the candidate vaccine, other known contraindications)
11. with clinical conditions representing a contraindication to intramuscular vaccination and blood draws
12. pregnant or lactating at the time of enrollment
13. Donation of blood, blood fractions or plasma within 30 days or received blood-derived products (e.g. plasma) within 90 days prior to vaccination in this study or planned to donate blood or used blood products until Day 180 of the study
14. rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating
15. known or suspected problem with alcohol or drug abuse as determined by the Investigator
16. any condition that, in the opinion of the Investigator, could compromise the subjects well-being, interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study;
17. committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities)
18. Participation in another clinical study involving an investigational medicinal product (IMP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IMP, or device during the course of this study
19. member of the team conducting the study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the Investigator or site personnel conducting the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination	Seroprotection rate, based on a surrogate of protection agreed with FDA Assay used for analysis was based on µPRNT (Micro Plaque Reduction Neutralization Test). Participants at pre-selected sites were included, if they had available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response.	on Day 29 after single vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unsolicited AEs	Number of Participants with Unsolicited Adverse Events	Until Day 29
Solicited Injection Site AEs	Number of Participants with solicited injection site reactions	within 10 days post-vaccination
Solicited Systemic AEs	Number of Participants with solicited systemic reactions	within 10 days post-vaccination
CHIKV-specific Neutralizing Antibody Titers	CHIKV-specific Neutralizing Antibody Titers on Day 8, and Day 29 Postvaccination as Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) Assay	Until Day 180
Number of Participants With Seroprotective CHIKV Antibody Level	Seroprotection rate, based on a surrogate of protection agreed with FDA Seroprotective CHIKV Antibody Level Defined as μPRNT (Micro Plaque Reduction Neutralization Test) for Baseline Negative Subjects	Until Day 180
Number of Participants With Seroconversion	Seroconversion was defined as CHIKV-specific neutralizing antibody titer of ≥ 20 based on µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects	Until Day 180
Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline	Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline	until Day 180
Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline	Number of Participants Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline	until Day 180
Adverse Events	Number of Participants with any Adverse Events	until Day 180
Related Adverse Events	Number of Participants with any related Adverse Events	until Day 180
Serious Adverse Event	Number of Participants with any Serious Adverse Events	until Day 180
Related Serious Adverse Event	Number of Participants with any Related Serious Adverse Events	until Day 180
Adverse Event of Special Interest	Number of Participants with any Adverse Event of Special Interest AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: 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.	within 21 days post-vaccination
Related Adverse Event of Special Interest	Number of Participants with any Related Adverse Event of Special Interest AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: 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.	within 21 days post-vaccination

Collaborators and Investigators

• Sponsor: Valneva Austria GmbH
• Investigators: Study Chair: Valneva Clinical Development, Valneva Austria GmbH

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2020
• Primary Completion (Actual): May 19, 2021
• Study Completion (Actual): October 15, 2021

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: CHIKV; VLA1553; Chikungunya Virus Infection; Live-attenuated Chikungunya virus vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Arbovirus Infections; Vector Borne Diseases; Alphavirus Infections; Togaviridae Infections; Virus Diseases; Chikungunya Fever
• Other Study ID Numbers: VLA1553-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No