A Phase 2 Clinical Trial of VLA1553 in Healthy Children Aged 1 to 11 Years

A Randomized, Observer-blinded, Dose Response Phase 2 Trial to Assess the Safety and Immunogenicity of Two Different Dose Levels of a Live-attenuated Chikungunya Virus Vaccine (VLA1553) in Healthy Children Aged 1 to 11 Years

This is a multicenter, prospective, randomized, observer-blinded, three arm, phase 2 clinical trial evaluating the full dose formulation of VLA1553, half dose formulation of VLA1553 and control.

At least 300 male and female healthy children aged 1 to 11 years will be enrolled and the overall distribution of participants will be 2:2:1 to the two VLA1553 dose groups (n=120 each) or control (n=60).

This is a multicenter, prospective, randomized, observer-blinded, three arm, phase 2 clinical trial evaluating the full dose formulation of VLA1553, half dose formulation of VLA1553 and control (Nimenrix, a tetravalent meningococcal vaccine - Men ACWY).

At least 300 male and female healthy children aged 1 to 11 years will be enrolled and the overall distribution of participants will be 2:2:1 to the two VLA1553 dose groups (n=120 each) or control (Nimenrix) (n=60).

As a safety precaution measure, the first 30 sentinel participants will be enrolled into the trial in an open-label fashion according to an age step down scheme.

After sentinel analysis, participants will be enrolled in a blinded, randomized manner into three Trial Arms. Within each treatment arm participants will be stratified into three age strata:

Stratum A: 7 to 11 years -children from their 7th birthday until the day before their 12th birthday.

Stratum B: 3 to 6 years - children from their 3rd birthday until the day before their 7th birthday.

Stratum C: 1 to 2 years - children from their 1st birthday until the day before their 3rd birthday.

Age strata for the VLA1553 treatment arms are targeted to be equal in size, i.e., approximately 40 per age stratum.

Inclusion Criteria:

1. Male or female healthy children aged 7 to 11 years for Stratum A, 3 to 6 years for Stratum B and 1 to 2 years for Stratum C at the time of vaccination;
2. Written informed consent by the participant's parent(s)/Legally Acceptable Representative(s) ((LAR(s)), according to local requirements, and written informed assent of the participant, if applicable;
3. Participant was seropositive for previous CHIKV exposure (i.e., IgM+/IgG+ or IgM-/IgG+) or seronegative (i.e., IgM-/IgG-); or participants with any borderline IgM or IgG element (IgM borderline/IgG-, IgM-/IgG borderline, or IgM borderline/IgG borderline were mapped to seronegative group; participants with enzyme-linked immunosorbent assay (ELISA) result IgM borderline/IgG+ were mapped to seropositive group);

Exclusion Criteria:

1. Participant was IgM+/IgG- does not qualify for participation in this trial.
2. Participant was taking medication or other treatment for unresolved symptoms attributed to a previous CHIKV infection; or had participated in a clinical trial involving an investigational CHIKV vaccine;
3. Participant had an acute or recent infection (and was not symptom-free in the week prior to the Screening Visit (Visit 0))
4. Participant had received another live virus vaccine within 28 days or inactivated vaccine (includes messenger ribonucleic acid [mRNA] vaccines) within 14 days prior to vaccination in this trial or planned to receive a live virus vaccine within 28 days or inactivated vaccine within 14 days after vaccination;
5. Participant had abnormal findings in any required trial investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator which posed a risk for participation in the trial based on his/her judgment;
6. Participant had an ongoing medical history of or currently had acute or progressive, unstable or uncontrolled clinical conditions (e.g., cardiovascular, respiratory, neurologic, psychiatric, or rheumatologic conditions) that posed a risk for participation in the trial, based on Investigator's clinical judgment. Examples included individuals with poorly controlled or unstable disease, ongoing suspected or active inflammation, or poor compliance with pharmacologic treatment, or presence of high-risk comorbidities (e.g., significant cardiopulmonary disease);
7. Participant had a history of immune-mediated or clinically relevant arthritis/arthralgia;
8. Participant had a known or suspected defect of the immune system that could be expected to influence the immune response to the vaccine, such as Participants with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno- suppressive therapy within 4 weeks prior to Visit 1. Immunosuppressive therapy was defined as administration of chronic (longer than 14 days) prednisone or equivalent ≥0.05 mg/kg/day within 4 weeks prior to trial entry, radiation therapy or immunosuppressive cytotoxic drugs/ monoclonal antibodies in the previous 3 years; topical and inhaled steroids were allowed.
9. Participant had a history of any vaccine-related contraindicating event (e.g., anaphylaxis, allergy to components of the vaccine or the control vaccine, other known contraindications including febrile convulsions);
10. Participant presented with clinical conditions representing severe bleeding disorders and medications interfering with blood clotting;
11. Participant received blood-derived products (e.g. plasma) within 180 days prior to vaccination in this trial;
12. Participant had participated in another clinical trial involving an investigational medicinal product (IMP) or device within 30 days prior to vaccination or was scheduled to participate in another clinical trial involving an IMP, or device during the course of this trial;
13. Participant had any condition that, in the opinion of the Investigator, could compromise the participant's well-being, might interfere with evaluation of trial endpoints, or would limit the participant's ability to complete the trial;
14. Participant/ Participant's parent(s)/LAR(s) was/were a member of the team conducting the trial or in a dependent relationship with one of the trial team members. Dependent relationships included close relatives (i.e., children, partner/spouse, siblings, parent(s)/LAR[s]) as well as employees of the Investigator or site personnel conducting the trial.