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

NCT ID: NCT04650399

Last Updated: 2024-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 750 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-31
• Study Completion Date: 2024-02-15

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.

Conditions

Chikungunya

Study Design

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

Study Groups

Active

VLA1553

Group Type: EXPERIMENTAL

Active

Intervention Type: BIOLOGICAL

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

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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

Interventions

Active

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. 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Valneva Austria GmbH

INDUSTRY

Sponsor Role: collaborator

Butantan Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fernanda Boulos, MD, MSc

Role: STUDY_CHAIR

Butantan Institute

Valneva Austria GmbH

Role: STUDY_DIRECTOR

Valneva Austria GmbH

Locations

CECOR - Centro Oncológico de Roraima

Boa Vista, Acre, Brazil

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Manaus, Amazonas, Brazil

Núcleo de Medicina Tropical - Universidade Federal do Ceará

Fortaleza, Ceará, Brazil

Associação Obras Sociais Irmã Dulce / Centro de Pesquisa Clínica - CPEC

Salvador, Estado de Bahia, Brazil

Centro de Pesquisa e Desenvolvimento de Fármacos (CPDF) - Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas

Belo Horizonte, Minas Gerais, Brazil

Real Hospital Português de Beneficência em Pernambuco

Recife, Pernambuco, Brazil

Centro de Pesquisas Clínicas Universidade Federal Sergipe

Aracaju, Sergipe, Brazil

Faculdade de Medicina de São José do Rio Preto - FAMERP

São José do Rio Preto, São Paulo, Brazil

Centro de Pesquisa Clínica da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul - UFMS

Campo Grande, , Brazil

Centro de Estudos do Instituto de Infectologia Emílio Ribas

São Paulo, , Brazil

Countries

Brazil

References

Buerger V, Hadl S, Schneider M, Schaden M, Hochreiter R, Bitzer A, Kosulin K, Mader R, Zoihsl O, Pfeiffer A, Loch AP, Morandi E Jr, Nogueira ML, de Brito CAA, Croda J, Teixeira MM, Coelho IC, Gurgel R, da Fonseca AJ, de Lacerda MVG, Moreira ED Jr, Veiga APR, Dubischar K, Wressnigg N, Eder-Lingelbach S, Jaramillo JC. Safety and immunogenicity of a live-attenuated chikungunya virus vaccine in endemic areas of Brazil: interim results of a double-blind, randomised, placebo-controlled phase 3 trial in adolescents. Lancet Infect Dis. 2025 Jan;25(1):114-125. doi: 10.1016/S1473-3099(24)00458-4. Epub 2024 Sep 5.

Reference Type: DERIVED

PMID: 39243794 (View on PubMed)

Other Identifiers

VLA1553-321

Identifier Type: -

Identifier Source: org_study_id