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

NCT ID: NCT04546724

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-17
• Study Completion Date: 2021-10-15

Brief Summary

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.

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.

Conditions

Chikungunya Virus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

VLA1553

Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose

Group Type: ACTIVE_COMPARATOR

VLA1553

Intervention Type: BIOLOGICAL

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo

Interventions

VLA1553

Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose

Intervention Type: BIOLOGICAL

Placebo

Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Valneva Austria GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valneva Clinical Development

Role: STUDY_CHAIR

Valneva Austria GmbH

Locations

Accelerated Enrollment Solutions (AES)

Chandler, Arizona, United States

Accelerated Enrollment Solutions (AES)

Phoenix, Arizona, United States

Alliance for Multispecialty Research (AMR)

Tempe, Arizona, United States

ELITE Research Network (ELITE)

Little Rock, Arkansas, United States

Velocity Clinical Research, Chula Vista

Chula Vista, California, United States

Accelerated Enrollment Solutions (AES)

San Diego, California, United States

Accel Research Sites - DeLand

DeLand, Florida, United States

ELITE Research Network (ELITE)

Hallandale, Florida, United States

Meridien Research - Maitland

Maitland, Florida, United States

Accelerated Enrollment Solutions (AES)

Melbourne, Florida, United States

Suncoast Research Group, LLC

Miami, Florida, United States

ELITE Research Network (ELITE)

North Miami Beach, Florida, United States

Jacksonville Center for Clinical Research, LTD dba St. Johns Center for Clinical Research

Ponte Vedra, Florida, United States

Synexus - The Villages

The Villages, Florida, United States

ELITE Research Network (ELITE)

Meridian, Idaho, United States

Accelerated Enrollment Solutions (AES)

Chicago, Illinois, United States

Accelerated Enrollment Solutions (AES)

Peoria, Illinois, United States

Alliance for Multispecialty Research (AMR)

El Dorado, Kansas, United States

Alliance for Multispecialty Research (AMR)

Newton, Kansas, United States

Alliance for Multispecialty Research (AMR)

Wichita, Kansas, United States

Alliance for Multispecialty Research (AMR)

Lexington, Kentucky, United States

AMR - New Orleans - Center for Clinical Research

New Orleans, Louisiana, United States

Alliance for Multispecialty Research (AMR)

Kansas City, Missouri, United States

Meridian Clinical Research - Grand Island

Grand Island, Nebraska, United States

Platinum Research Network (Platinum)

Omaha, Nebraska, United States

Accelerated Enrollment Solutions (AES)

Omaha, Nebraska, United States

Alliance for Multispecialty Research (AMR)

Las Vegas, Nevada, United States

Meridian Clinical Research

Endwell, New York, United States

Rochester Clinical Research

Rochester, New York, United States

Lucas Research

Morehead City, North Carolina, United States

ELITE Research Network (ELITE)

Wilmington, North Carolina, United States

Accelerated Enrollment Solutions (AES)

Cincinnati, Ohio, United States

ELITE Research Network (ELITE)

Oklahoma City, Oklahoma, United States

Velocity Clinical Research - Medford

Medford, Oregon, United States

Synexus - Anderson

Anderson, South Carolina, United States

Vitalink Research - Anderson

Anderson, South Carolina, United States

Alliance for Multispecialty Research (AMR)

Knoxville, Tennessee, United States

Tekton Research - Beaumont

Beaumont, Texas, United States

PanAmerican Clinical Research - US Headquarter

Brownsville, Texas, United States

Velocity Clinical Research - Austin

Cedar Park, Texas, United States

Research Your Health, LLC

Plano, Texas, United States

ELITE Research Network (ELITE)

Tomball, Texas, United States

ELITE Research Network (ELITE)

West Jordan, Utah, United States

Alliance for Multispecialty Research (AMR)

Norfolk, Virginia, United States

Countries

United States

References

Kosulin K, Brasel TL, Smith J, Torres M, Bitzer A, Dubischar K, Buerger V, Mader R, Weaver SC, Beasley DWC, Hochreiter R. Cross-neutralizing activity of the chikungunya vaccine VLA1553 against three prevalent chikungunya lineages. Emerg Microbes Infect. 2025 Dec;14(1):2469653. doi: 10.1080/22221751.2025.2469653. Epub 2025 Mar 10.

Reference Type: DERIVED

PMID: 39998495 (View on PubMed)

Schneider M, Narciso-Abraham M, Hadl S, McMahon R, Toepfer S, Fuchs U, Hochreiter R, Bitzer A, Kosulin K, Larcher-Senn J, Mader R, Dubischar K, Zoihsl O, Jaramillo JC, Eder-Lingelbach S, Buerger V, Wressnigg N. Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 24;401(10394):2138-2147. doi: 10.1016/S0140-6736(23)00641-4. Epub 2023 Jun 12.

Reference Type: DERIVED

PMID: 37321235 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VLA1553-301

Identifier Type: -

Identifier Source: org_study_id