Clinical trial NCT04650399: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chikungunya
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Valneva Austria GmbH
First posted: 2020-12-02
Enrollment: 750
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Seroprotection
timeFrame: up to Day 29 after single vaccination
Secondary outcomes:
measure: Immunogenicity
timeFrame: until Day 8, Day 85, Day 180, and Month 12 after vaccination
measure: Seroprotection up to 1 year
timeFrame: until Day 8, Day 29, Day 85, Day 180, and Month 12 after vaccination
measure: Seroconversion up to 1 year
timeFrame: 12 months after vaccination
measure: Fold Increase in neutralizing antibodies
timeFrame: 12 months after vaccination
measure: Proportion of increase of neutralizing antibodies
timeFrame: 12 months after vaccination
measure: Immunogenicity per baseline serostatus
timeFrame: 12 months after vaccination
measure: Unsolicited adverse events
timeFrame: 6 months after vaccination
measure: Solicited adverse reactions
timeFrame: 10 days after vaccination
measure: Frequency of adverse event of special interest
timeFrame: until 12 month after vaccination
measure: Viremia of vaccine strain
timeFrame: 29 days after vaccination
measure: Frequency of Serious Adverse Event
timeFrame: until 12 month after vaccination
Other outcomes:
Locations:
city: Boa Vista
country: Brazil
facility: CECOR - Centro Oncológico de Roraima
state: Acre
city: Manaus
country: Brazil
facility: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
state: Amazonas
city: Salvador
country: Brazil
facility: Associação Obras Sociais Irmã Dulce / Centro de Pesquisa Clínica - CPEC
state: Bahia
city: Fortaleza
country: Brazil
facility: Núcleo de Medicina Tropical - Universidade Federal do Ceará
state: Ceará
city: Belo Horizonte
country: Brazil
facility: Centro de Pesquisa e Desenvolvimento de Fármacos (CPDF) - Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas
state: Minas Gerais
city: Recife
country: Brazil
facility: Real Hospital Português de Beneficência em Pernambuco
state: Pernambuco
city: Aracaju
country: Brazil
facility: Centro de Pesquisas Clínicas Universidade Federal Sergipe
state: Sergipe
city: São José Do Rio Preto
country: Brazil
facility: Faculdade de Medicina de São José do Rio Preto - FAMERP
state: São Paulo
city: Campo Grande
country: Brazil
facility: Centro de Pesquisa Clínica da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul - UFMS
city: São Paulo
country: Brazil
facility: Centro de Estudos do Instituto de Infectologia Emílio Ribas
Study officials:
affiliation: Butantan Institute
name: Fernanda Boulos, MD, MSc
role: STUDY_CHAIR
affiliation: Valneva Austria GmbH
name: Valneva Austria GmbH
role: STUDY_DIRECTOR
References: