Clinical trial NCT04546724: Pivotal Study to Evaluate Safety and Immunogenicity of a Live-Attenuated Chikungunya Virus Vaccine Candidate in Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chikungunya Virus Infection
Keywords: VLA1553
Chikungunya Virus Infection
CHIKV
Live-attenuated Chikungunya virus vaccine
Lead sponsor: Valneva Austria GmbH
Sponsor class: INDUSTRY
First posted: 2020-09-14
Enrollment: 4128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

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.

Primary outcomes:
measure: Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination
timeFrame: on Day 29 after single vaccination
Secondary outcomes:
measure: CHIKV-specific Neutralizing Antibody Titers
timeFrame: Until Day 180
measure: Number of Participants With Seroprotective CHIKV Antibody Level
timeFrame: Until Day 180
measure: Number of Participants With Seroconversion
timeFrame: Until Day 180
measure: Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline
timeFrame: until Day 180
measure: Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline
timeFrame: until Day 180
measure: Unsolicited AEs
timeFrame: Until Day 29
measure: Solicited Injection Site AEs
timeFrame: within 10 days post-vaccination
measure: Solicited Systemic AEs
timeFrame: within 10 days post-vaccination
measure: Adverse Events
timeFrame: until Day 180
measure: Related Adverse Events
timeFrame: until Day 180
measure: Serious Adverse Event
timeFrame: until Day 180
measure: Related Serious Adverse Event
timeFrame: until Day 180
measure: Adverse Event of Special Interest
timeFrame: within 21 days post-vaccination
measure: Related Adverse Event of Special Interest
timeFrame: within 21 days post-vaccination
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Arizona
city: Phoenix
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Arizona
city: Tempe
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Arizona
city: Little Rock
country: United States
facility: ELITE Research Network (ELITE)
state: Arkansas
city: Chula Vista
country: United States
facility: Velocity Clinical Research, Chula Vista
state: California
city: San Diego
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: California
city: DeLand
country: United States
facility: Accel Research Sites - DeLand
state: Florida
city: Hallandale Beach
country: United States
facility: ELITE Research Network (ELITE)
state: Florida
city: Maitland
country: United States
facility: Meridien Research - Maitland
state: Florida
city: Melbourne
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC
state: Florida
city: North Miami Beach
country: United States
facility: ELITE Research Network (ELITE)
state: Florida
city: Ponte Vedra
country: United States
facility: Jacksonville Center for Clinical Research, LTD dba St. Johns Center for Clinical Research
state: Florida
city: The Villages
country: United States
facility: Synexus - The Villages
state: Florida
city: Meridian
country: United States
facility: ELITE Research Network (ELITE)
state: Idaho
city: Chicago
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Illinois
city: Peoria
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Illinois
city: El Dorado
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Kansas
city: Newton
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Kansas
city: Lexington
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Kentucky
city: New Orleans
country: United States
facility: AMR - New Orleans - Center for Clinical Research
state: Louisiana
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Missouri
city: Grand Island
country: United States
facility: Meridian Clinical Research - Grand Island
state: Nebraska
city: Omaha
country: United States
facility: Platinum Research Network (Platinum)
state: Nebraska
city: Omaha
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Nebraska
city: Las Vegas
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Nevada
city: Endwell
country: United States
facility: Meridian Clinical Research
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Morehead City
country: United States
facility: Lucas Research
state: North Carolina
city: Wilmington
country: United States
facility: ELITE Research Network (ELITE)
state: North Carolina
city: Cincinnati
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Ohio
city: Oklahoma City
country: United States
facility: ELITE Research Network (ELITE)
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research - Medford
state: Oregon
city: Anderson
country: United States
facility: Synexus - Anderson
state: South Carolina
city: Anderson
country: United States
facility: Vitalink Research - Anderson
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Tennessee
city: Beaumont
country: United States
facility: Tekton Research - Beaumont
state: Texas
city: Brownsville
country: United States
facility: PanAmerican Clinical Research - US Headquarter
state: Texas
city: Cedar Park
country: United States
facility: Velocity Clinical Research - Austin
state: Texas
city: Plano
country: United States
facility: Research Your Health, LLC
state: Texas
city: Tomball
country: United States
facility: ELITE Research Network (ELITE)
state: Texas
city: West Jordan
country: United States
facility: ELITE Research Network (ELITE)
state: Utah
city: Norfolk
country: United States
facility: Alliance for Multispecialty Research (AMR)
state: Virginia
Study officials:
affiliation: Valneva Austria GmbH
name: Valneva Clinical Development
role: STUDY_CHAIR
References: