The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04546724
Recruitment Status : Completed
First Posted : September 14, 2020
Results First Posted : July 25, 2022
Last Update Posted : June 28, 2023
Sponsor:
Information provided by (Responsible Party):
Valneva Austria GmbH

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.

Condition or disease Intervention/treatment Phase
Chikungunya Virus Infection Biological: VLA1553 Biological: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4128 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 : September 17, 2020
Actual Primary Completion Date : May 19, 2021
Actual Study Completion Date : October 15, 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination [ Time Frame: on Day 29 after single 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.



Secondary Outcome Measures :
  1. CHIKV-specific Neutralizing Antibody Titers [ Time Frame: Until Day 180 ]
    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 [ Time Frame: Until Day 180 ]
    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 [ Time Frame: Until Day 180 ]
    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 [ Time Frame: until Day 180 ]
    Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by μPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline

  5. Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline [ Time Frame: until Day 180 ]
    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 [ Time Frame: Until Day 29 ]
    Number of Participants with Unsolicited Adverse Events

  7. Solicited Injection Site AEs [ Time Frame: within 10 days post-vaccination ]
    Number of Participants with solicited injection site reactions

  8. Solicited Systemic AEs [ Time Frame: within 10 days post-vaccination ]
    Number of Participants with solicited systemic reactions

  9. Adverse Events [ Time Frame: until Day 180 ]
    Number of Participants with any Adverse Events

  10. Related Adverse Events [ Time Frame: until Day 180 ]
    Number of Participants with any related Adverse Events

  11. Serious Adverse Event [ Time Frame: until Day 180 ]
    Number of Participants with any Serious Adverse Events

  12. Related Serious Adverse Event [ Time Frame: until Day 180 ]
    Number of Participants with any Related Serious Adverse Events

  13. Adverse Event of Special Interest [ Time Frame: within 21 days post-vaccination ]

    Number of Participants with any Adverse Event of Special Interest

    AESI Definition:

    The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration:

    1. Fever (≥38.0°C [100.4°F] measured orally) and
    2. Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus [foot plant] and edema of the face and extremities), polyadenopathies; and
    3. Onset of symptoms 2 to 21 days after vaccination and
    4. Duration of event ≥3 days.

  14. Related Adverse Event of Special Interest [ Time Frame: within 21 days post-vaccination ]

    Number of Participants with any Related Adverse Event of Special Interest

    AESI Definition:

    The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration:

    1. Fever (≥38.0°C [100.4°F] measured orally) and
    2. Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus [foot plant] and edema of the face and extremities), polyadenopathies; and
    3. Onset of symptoms 2 to 21 days after vaccination and
    4. Duration of event ≥3 days.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04546724


Locations
Show Show 44 study locations
Sponsors and Collaborators
Valneva Austria GmbH
Investigators
Layout table for investigator information
Study Chair: Valneva Clinical Development Valneva Austria GmbH
  Study Documents (Full-Text)

Documents provided by Valneva Austria GmbH:
Study Protocol  [PDF] March 23, 2021
Statistical Analysis Plan  [PDF] January 14, 2022

Layout table for additonal information
Responsible Party: Valneva Austria GmbH
ClinicalTrials.gov Identifier: NCT04546724    
Other Study ID Numbers: VLA1553-301
First Posted: September 14, 2020    Key Record Dates
Results First Posted: July 25, 2022
Last Update Posted: June 28, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Virus Diseases
Chikungunya Fever
Infections
Alphavirus Infections
Arbovirus Infections
Vector Borne Diseases
Mosquito-Borne Diseases
Togaviridae Infections
RNA Virus Infections