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

Valneva Austria GmbH304 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

304

Conditions

Chikungunya Virus Infection

Interventions

VLA1553 full doseBIOLOGICAL

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

VLA1553 half doseBIOLOGICAL

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

ControlBIOLOGICAL

Nimenrix

Eligibility

Sex: ALLMin age: 1 YearMax age: 11 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (3)

Fundacion Dominicana de Perinatologia Fundacion Probebe

Santo Domingo, Gazcue, Dominican Republic

Instituto Dermatologico y Cirugia de la Piel "Dr Huberto Bogaert Diaz" IDCP

Santo Domingo, Dominican Republic

Inversiones en Investigacion Medica INVERIME

Tegucigalpa, Honduras

Outcomes

Primary Outcomes

Number of Participants With Solicited Injection Site Reactions

Frequency and severity of solicited injection site and solicited systemic reactions within 14 days post-vaccination.

Time frame: within 14 days post-vaccination

Severity of Solicited Injection Site Reactions

Time frame: within 14 days post-vaccination

Number of Participants With Solicited Systemic Reactions

Time frame: within 14 days post-vaccination

Severity of Solicited Systemic Reactions

Time frame: within 14 days post-vaccination

Secondary Outcomes

Number of Participants With Any Adverse Event (AE)

Time frame: within 28 days post-vaccination

Severity of Any Adverse Event (AE)

In the Outcome measure "Severity of any AE", subjects may be represented in more than one AE category. Therefore, the total number of subjects with any AE may be lower than the sum of the numbers of subjects in the individual AE categories (solicited / unsolicited AE).

Time frame: within 28 days post-vaccination

Number of Participants With of Unsolicited AE

Time frame: until Month 6 (Day 180) and Month 12 (Day 365) post-vaccination

Severity of Unsolicited AE

Time frame: until Month 6 (Day 180) and Month 12 (Day 365) post-vaccination

Number of Participants With Any Serious Adverse Event (SAE)

Data from ClinicalTrials.gov

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Time frame: until Month 6 (Day 180) and Month 12 (Day 365) post-vaccination

Number of Participants With Any Early Onset Adverse Event of Special Interest (AESI)

Early onset AESI were defined as: 1. Fever (≥ 38.0 °c / 100.4 °f,) AND 2. symptoms suggesting acute (poly)arthralgia/arthritis, myalgia, neurological symptoms (e.g., for meningoencephalitis, acute encephalitis, headache, seizures), back pain, lymphadenopathy, cardiac or ocular symptoms (e.g., for uveitis and retinitis); OR one or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus \[foot plant\]), pigmentary changes, bullous rash/ skin blistering, purpura, ecchymosis and 3. Onset of symptoms 2 to 21 days after vaccination AND 4. Duration of event ≥ 3 days.

Time frame: 2 to 21 days post-vaccination

Severity of Any Early Onset Adverse Event of Special Interest (AESI)

Time frame: 2 to 21 days post-vaccination

Number of Participants With Any Late Onset Adverse Event of Special Interest (AESI)

Time frame: Starting 22 days post-vaccination until end of trial, 12 months post-vaccination

Severity of Any Late Onset Adverse Event of Special Interest (AESI)

Time frame: Starting 22 days post-vaccination until end of trial, 12 months post-vaccination

Assessment of Viremia on Days 1, 4, 8 and 15

Number of participants with viremic results, including quantifiable results and results below LLOQ, by visit and by pooled trial arm. Day 29 was only tested, if Day 15 was tested positive. Viremia is measured in genome copy equivalents per milliliter (GCE/mL). All quantifiable results and results below LLOQ (\< 3214.4 GCE/mL), but above the LOD, are considered "viremic". A result of "not detected" or below LOD (\<1071,4 GCE/mL) is included as "non-viremic".

Time frame: on Days 1, 4, 8 and 15 and beyond as applicable

Immune Response in Baseline Seronegative Participants as Measured by CHIKV-specific Neutralizing Antibody Titers

Immune Response provided by Geometric Mean Titers (GMTs) in Baseline Seronegative Participants pooled by Trial Arm up to 12 months post vaccination.

Time frame: on Day 1, Day 15, Day 29, Day 85, Day 180 and Month 12 post-vaccination

Immune Response as Measured by CHIKV-specific Neutralizing Antibody Titers by Age Group and Trial Arm.

Immune Response provided by Geometric Mean Titers (GMTs) by Visit, by Age Group and Trial Arm up to 12 months post vaccination.

Time frame: on Day 1, Day 15, Day 29, Day 85, Day 180 and Month 12 post-vaccination

Immune Response Measured by CHIKV-specific Neutralizing Antibody Titers Pooled by Dose

Immune Response provided by Geometric Mean Titers (GMTs) by Visit, pooled by Trial Arm up to 12 months post vaccination.

Time frame: on Day 1, Day 15, Day 29, Day 85, Day 180 and Month 12 post-vaccination

Percentage of Participants Seronegative at Baseline With Seroconversion as Compared to Baseline

Percentage of participants seronegative at baseline with Seroconversion (defined as \>4-fold titer change compared to baseline) by Visit Pooled by Trial Arm

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12

Percentage of Participants Seropositive at Baseline With Seroconversion as Compared to Baseline

Percentage of participants seropositive at baseline with Seroconversion (defined as \>4-fold titer change compared to baseline) by Visit Pooled by Trial Arm.

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12

Percentage of Participants With Seroconversion as Compared to Baseline Stratified by Age Stratum

Percentage of participants with Seroconversion (defined as \>4-fold titer change compared to baseline) by Visit by Age Group and Trial Arm.

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12

Percentage of Participants With Seroconversion as Compared to Baseline by Dose

Percentage of participants with Seroconversion (defined as \>4-fold titer change compared to baseline) by Visit Pooled by Trial Arm

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12

Percentage of Participants Seronegative at Baseline With a Seroresponse (Defined as PRNT50 ≥150 for Baseline Negative Participants) by Dose

Percentage of Participants with Seroresponse for CHIKV-Specific Neutralizing Antibody Titers (defined as PRNT50 ≥150) by Visit Pooled by Trial Arm.

Time frame: on Day 15, Day 29, Day 85, Day 180 and Month 12 post-vaccination

Percentage of Participants With a Seroresponse Stratified by Age Stratum

Percentage of Participants with Seroresponse for CHIKV-Specific Neutralizing Antibody Titers (defined as PRNT50 ≥150) by Visit by Age Group and Trial Arm.

Time frame: on Day 15, Day 29, Day 85, Day 180 and Month 12 post-vaccination

Percentage of Participants With a Seroresponse Stratified by Dose

Percentage of Participants with Seroresponse for CHIKV-Specific Neutralizing Antibody Titers (defined as PRNT50 ≥150) by Visit Pooled by Trial Arm.

Time frame: on Day 15, Day 29, Day 85, Day 180 and Month 12 post-vaccination

Fold Change of CHIKV-specific Neutralizing Antibody Titers as Compared to Baseline in Participants Seronegative at Baseline

Fold Change for CHIKV-Specific Neutralizing Antibody Titers in seronegative Participants by Visit Pooled by Trial Arm.

Time frame: at Days 15, 29, 85, 180 and at Month 12 post-vaccination

Fold Change of CHIKV-specific Neutralizing Antibody Titers as Compared to Baseline in Seropositive Participants

Fold Change for CHIKV-Specific Neutralizing Antibody Titers in seropositive Participants by Visit Pooled by Trial Arm.

Time frame: at Days 15, 29, 85, 180 and at Month 12 post-vaccination

Fold Change of CHIKV-specific Neutralizing Antibody Titers as Compared to Baseline Stratified by Age Stratum

Fold Change for CHIKV-Specific Neutralizing Antibody Titers by Visit by Age Group and Trial Arm.

Time frame: at Days 15, 29, 85, 180 and at Month 12 post-vaccination

Fold Change of CHIKV-specific Neutralizing Antibody Titers as Compared to Baseline Stratified by Dose

Fold Change for CHIKV-Specific Neutralizing Antibody Titers by Visit Pooled by Trial Arm.

Time frame: at Days 15, 29, 85, 180 and at Month 12 post-vaccination

Percentage of Participants Seronegative at Baseline Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold Change in CHIKV-specific Neutralizing Antibody Titers Compared to Baseline

Percentage of Participants Reaching a 4-/8-/16-/64-Fold Change in Titers by Visit Pooled by Trial Arm.

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12

Percentage of Participants Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold Change in CHIKV-specific Neutralizing Antibody Titers Compared to Baseline Stratified by Age Stratum

Percentage of Participants Reaching a 4-/8-/16-/64-Fold Change in Titers by Visit by Age Group and Trial Arm.

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12

Percentage of Participants Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold Change in CHIKV-specific Neutralizing Antibody Titers Compared to Baseline by Dose

Percentage of Participants Reaching a 4-/8-/16-/64-Fold Change in Titers by Visit Pooled by Trial Arm.

Time frame: at Day 15, Day 29, Day 85, Day 180 and Month 12