A Multicenter Study to Evaluate Safety and Immunogenicity of a Live-attenuated Chikungunya Vaccine in Adolescents

• ClinicalTrials.gov Identifier: NCT04650399
• Recruitment Status: Completed
• First Posted: December 2, 2020
• Last Update Posted: May 3, 2024
• Sponsor: Butantan Institute
• Collaborator: Valneva Austria GmbH
• Information provided by (Responsible Party): Butantan Institute

Tracking Information

• First Submitted Date: November 25, 2020
• First Posted Date: December 2, 2020
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: January 31, 2022
• Actual Primary Completion Date: February 13, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 22, 2022)

Seroprotection [ Time Frame: up to Day 29 after single vaccination ]

Proportion of subjects with a seroprotective CHIKV antibody level determined by µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects 28 days post-vaccination.

Original Primary Outcome Measures (submitted: December 1, 2020)

Seroprotection [ Time Frame: 28 days after vaccination ]

Proportion of subjects with a seroprotective CHIKV antibody level defined as μPRNT50 ≥ 1:50 for baseline negative subjects 28 days post-vaccination.

Current Secondary Outcome Measures (submitted: November 17, 2022)

• Immunogenicity [ Time Frame: until Day 8, Day 85, Day 180, and Month 12 after vaccination ]
  Immune response as measured by CHIKV-specific neutralizing antibody titers determined by μPRNT assay
• Seroprotection up to 1 year [ Time Frame: until Day 8, Day 29, Day 85, Day 180, and Month 12 after vaccination ]
  Proportion of subjects with seroprotective CHIKV antibody levels as determined by µPRNT Month 12.
• Seroconversion up to 1 year [ Time Frame: 12 months after vaccination ]
  Proportion of subjects with seroconversion as compared to baseline at Day 29, Month 6 and Month 12 as determined by μPRNT assay
• Fold Increase in neutralizing antibodies [ Time Frame: 12 months after vaccination ]
  Fold increase of CHIKV-specific neutralizing antibody titers determined by μPRNT assay at Days 8, 29, 85, 180 and at Month 12 post-vaccination as compared to baseline
• Proportion of increase of neutralizing antibodies [ Time Frame: 12 months after vaccination ]
  Proportion of subjects reaching an at least 4-fold, 8-fold, 16-fold or 64-fold increase in CHIKV-specific neutralizing antibody titer compared to baseline as measured by μPRNT assay
• Immunogenicity per baseline serostatus [ Time Frame: 12 months after vaccination ]
  Antibody titers, seroprotection and fold increases for CHIKV-specific neutralizing antibodies, determined by μPRNT assay at Days 1, 8, 29, 85, 180, and Month 12 post-vaccination stratified by baseline serostatus
• Unsolicited adverse events [ Time Frame: 6 months after vaccination ]
  Frequency and severity of unsolicited AEs until Day 29 and Month 6 post-vaccination
• Solicited adverse reactions [ Time Frame: 10 days after vaccination ]
  Frequency and severity of solicited injection site and systemic reactions within ten days post-vaccination
• Frequency of adverse event of special interest [ Time Frame: until 12 month after vaccination ]
  Frequency and severity of any Adverse Event of Special Interest
• Viremia of vaccine strain [ Time Frame: 29 days after vaccination ]
  Frequency of viremia of vaccine strain detected on Days 1 and 8 (and Day 29, if applicable) after vaccination
• Frequency of Serious Adverse Event [ Time Frame: until 12 month after vaccination ]
  Frequency and relatedness of any Serious Adverse Event (SAE) during the entire study period

Original Secondary Outcome Measures (submitted: December 1, 2020)

• Immunogenicity [ Time Frame: 12 months after vaccination ]
  Immune response as measured by CHIKV-specific neutralizing antibody titers on Day 8, Day 29, Day 85, Day 180, and Month 12 post-vaccination as determined by μPRNT assay
• Seroprotection up to 1 year [ Time Frame: 12 months after vaccination ]
  Proportion of subjects with seroprotective levels (defined as μPRNT50 ≥ 1:50 for baseline negative subjects)i on Day 8, Day 85, Day 180 and Month 12 post-vaccination as determined by μPRNT assay;
• Seroconversion up to 1 year [ Time Frame: 12 months after vaccination ]
  Proportion of subjects with seroconversion as compared to baseline at Day 29 and Month 12 as determined by μPRNT assay;
• Increase in neutralizing antibodies [ Time Frame: 12 months after vaccination ]
  Fold increase of CHIKV-specific neutralizing antibody titers determined by μPRNT assay at Days 8, 29, 85, 180 and at Month 12 post-vaccination as compared to baseline
• Proportion of increase of neutralizing antibodies [ Time Frame: 12 months after vaccination ]
  Proportion of subjects reaching an at least 4-fold, 8-fold, 16-fold or 64-fold increase in CHIKV-specific neutralizing antibody titer compared to baseline as measured by μPRNT assay
• Immunogenicity per baseline serostatus [ Time Frame: 12 months after vaccination ]
  Antibody titers, seroprotection and fold increases for CHIKV-specific neutralizing antibodies, determined by μPRNT assay at Days 1, 8, 29, 85, 180, and Month 12 post-vaccination stratified by baseline serostatus
• Unsolicited adverse events [ Time Frame: 6 months after vaccination ]
  Frequency and severity of unsolicited AEs until Month 6 post-vaccination
• Solicited adverse reactions [ Time Frame: 10 days after vaccination ]
  Frequency and severity of solicited injection site and systemic reactions within ten days post-vaccination
• Frequency of adverse event of special interest [ Time Frame: 21 days afer vaccination ]
  Frequency and severity of any adverse event of special interest (AESI) within 2 to 21 days post-vaccination
• Viremia of vaccine strain [ Time Frame: 29 days after vaccination ]
  Frequency of viremia of vaccine strain detected on Days 1 and 8 (and Day 29, if applicable) after vaccination

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multicenter Study to Evaluate Safety and Immunogenicity of a Live-attenuated Chikungunya Vaccine in Adolescents
• Official Title: A Multicenter, Randomized, Controlled, Double Blinded Pivotal Study to Evaluate Safety and Immunogenicity of a Live-attenuated Chikungunya Virus Vaccine Candidate (VLA1553) in Adolescents Aged 12 Years to <18 Years
• Brief Summary: This is a prospective, randomized, double-blinded, multicenter, pivotal 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 750 male and female subjects aged 12 years to <18 years will be enrolled into the study.
• Detailed Description: This is a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study comprising approximately 750 subjects aged 12 years to <18 years randomized in a 2:1 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 by baseline serostatus. The primary objective of the study is to evaluate the immunogenicity and safety of the adult 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 12.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Chikungunya

Intervention

• Biological: Active
  Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate 1x10E4 TCID50 per dose
• Biological: Placebo
  Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo

Study Arms

• Experimental: Active
  VLA1553
  Intervention: Biological: Active
• Placebo Comparator: Placebo
  Placebo
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 1, 2020): 750
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 15, 2024
• Actual Primary Completion Date: February 13, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. From the 12th birthday to the last day before the 18th birthday on the Day of screening;
2. able to provide informed consent as well as written informed consent by the subject's legal representative ;
3. generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests;
4. seropositive for previous CHIKV exposure (i.e. IgM+/IgG+ or IgM-/IgG+) or seronegative (i.e. IgM-/IgG-) as screened by CHIKV-specific ELISA.

5. for women of childbearing potential:

   1. negative serum or urine pregnancy test at screening.
   2. practiced an adequate method of contraception during 30 days before screening
   3. agrees to employ adequate birth control measures for the first three months post-vaccination (i.e. until Day 85).

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. tests positive for human immunodeficiency virus (HIV) 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 17 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT04650399
• Other Study ID Numbers: VLA1553-321
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Butantan Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Butantan Institute
• Original Study Sponsor: Same as current
• Collaborators: Valneva Austria GmbH

Investigators

• Study Chair: Fernanda Boulos, MD, MSc; Butantan Institute
• Study Director: Valneva Austria GmbH; Valneva Austria GmbH

• PRS Account: Butantan Institute
• Verification Date: May 2024