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

Chikungunya Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04650399
• Other study ID #: VLA1553-321
• Status: Completed
• Phase: Phase 3
• Start date: January 31, 2022
• Est. completion date: February 15, 2024

Study information

• Verified date: May 2024
• Source: Butantan Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 750
• Est. completion date: February 15, 2024
• Est. primary completion date: February 13, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chikungunya
• Chikungunya Fever

Intervention

Biological:
• Active
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

Locations

Country	Name	City	State
Brazil	Centro de Pesquisas Clínicas Universidade Federal Sergipe	Aracaju	Sergipe
Brazil	Centro de Pesquisa e Desenvolvimento de Fármacos (CPDF) - Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas	Belo Horizonte	Minas Gerais
Brazil	CECOR - Centro Oncológico de Roraima	Boa Vista	Acre
Brazil	Centro de Pesquisa Clínica da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul - UFMS	Campo Grande
Brazil	Núcleo de Medicina Tropical - Universidade Federal do Ceará	Fortaleza	Ceará
Brazil	Fundação de Medicina Tropical Dr. Heitor Vieira Dourado	Manaus	Amazonas
Brazil	Real Hospital Português de Beneficência em Pernambuco	Recife	Pernambuco
Brazil	Associação Obras Sociais Irmã Dulce / Centro de Pesquisa Clínica - CPEC	Salvador	Bahia
Brazil	Faculdade de Medicina de São José do Rio Preto - FAMERP	São José Do Rio Preto	São Paulo
Brazil	Centro de Estudos do Instituto de Infectologia Emílio Ribas	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Butantan Institute	Valneva Austria GmbH

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seroprotection	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.	up to Day 29 after single vaccination
Secondary	Immunogenicity	Immune response as measured by CHIKV-specific neutralizing antibody titers determined by µPRNT assay	until Day 8, Day 85, Day 180, and Month 12 after vaccination
Secondary	Seroprotection up to 1 year	Proportion of subjects with seroprotective CHIKV antibody levels as determined by µPRNT Month 12.	until Day 8, Day 29, Day 85, Day 180, and Month 12 after vaccination
Secondary	Seroconversion up to 1 year	Proportion of subjects with seroconversion as compared to baseline at Day 29, Month 6 and Month 12 as determined by µPRNT assay	12 months after vaccination
Secondary	Fold Increase in neutralizing antibodies	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	12 months after vaccination
Secondary	Proportion of increase of neutralizing antibodies	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	12 months after vaccination
Secondary	Immunogenicity per baseline serostatus	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	12 months after vaccination
Secondary	Unsolicited adverse events	Frequency and severity of unsolicited AEs until Day 29 and Month 6 post-vaccination	6 months after vaccination
Secondary	Solicited adverse reactions	Frequency and severity of solicited injection site and systemic reactions within ten days post-vaccination	10 days after vaccination
Secondary	Frequency of adverse event of special interest	Frequency and severity of any Adverse Event of Special Interest	until 12 month after vaccination
Secondary	Viremia of vaccine strain	Frequency of viremia of vaccine strain detected on Days 1 and 8 (and Day 29, if applicable) after vaccination	29 days after vaccination
Secondary	Frequency of Serious Adverse Event	Frequency and relatedness of any Serious Adverse Event (SAE) during the entire study period	until 12 month after vaccination