COVID-19 Paediatric VLA2001-321 Study

Study Overview
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Brief Summary
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This is a Randomized, Double-blinded, Active-controlled Study to evaluate the Safety, Tolerability and Immunogenicity of VLA2001 in participants of ≥2 to 12 years. In total 1720 participants will receive either VLA2001 or active Comparator.

Detailed Description
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This is a Randomized, Double-blinded, Active-controlled Study to evaluate the Safety, Tolerability and Immunogenicity of VLA2001 in participants of ≥2 to 12 years. The study will consist of four parts: Dose-finding part (participants aged ≥5 to <12 years) Dose-finding part (participants aged ≥2 to <5 years) Confirmatory part (participants aged ≥5 to <12 years) Confirmatory part (participants aged ≥2 to <5 years) Dose-finding part (participants aged ≥5 to <12 years) Approximately 60 participants will receive 2 intramuscular doses of either half-dose VLA2001 (n=30) or full-dose VLA2001 (n=30) on Days 1 and 29 in a 1:1 ratio. Dose-finding part (participants aged ≥2 to <5 years) Approximately 60 participants will receive 2 intramuscular doses of either half-dose VLA2001 (n=30) or full-dose VLA2001 (n=30) on Days 1 and 29 in a 1:1 ratio. Dose-finding part for age group ≥2 to <5 years will be initiated after dose for age group ≥5 to <12 years is confirmed. Confirmatory Part (participants aged ≥5 to <12 years and ≥2 to <5 years) Overall, approximately 1600 participants aged ≥2 to <12 years will be enrolled. 800 participants aged ≥5 to <12 years and 800 participants aged ≥2 to <5 years will be randomized in 3:1 ratio. In each age group, 600 participants will receive VLA2001, and 200 participants comparator. Vaccination will start with either 1 intramuscular dose of VLA2001 (selected dose) or comparator vaccine. 28 days later all participants will receive a dose of VLA2001 (selected dose) and 28 days thereafter those who had received the comparator vaccine will receive their second dose with VLA2001 while those who have already received two doses of VLA2001 will receive the comparator vaccine.

Official Title
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A Randomized, Double-Blinded, Active Controlled COVID-19 Study to Evaluate The Safety, Tolerability, And Immunogenicity Of Different Doses Of VLA2001 Vaccine, In Children (≥2 To <12 Years)

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: VLA2001
* Drug: Active Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent by the participant's legal representative(s), according to local requirements, and written informed assent of the participant, if applicable, prior to any study related procedures. Participants of either gender aged between 2 years and <12 years at screening. Regarding history of Menactra (meningococcal vaccination): only participants <5 years can be included who received no Menactra vaccination. Participants ≥5 years can be included, if at least 4 years have elapsed since the prior dose. Medically stable such that, according to the judgment of the investigator the participant appears likely to be able to remain on study through the end of protocol-specified follow-up. • For participants with chronic diseases (such as, asthma, diabetes mellitus, cystic fibrosis, human immunodeficiency virus [HIV] infection), the disease should be stable, defined as not requiring significant change in therapy or hospitalization for worsening disease during the 3 months prior to the expected day of randomization (Visit 1) and as per investigator assessment. Must be able to attend all visits of the study and comply with all study procedures, including daily completion of the e-Diary after each vaccination. Female participants of non-childbearing potential may be enrolled. For this study, non-childbearing potential is defined as pre-menarche. Female participants of childbearing potential (WOCBP) might be enrolled if: have a negative pregnancy test on the day of vaccination, have practiced adequate contraception* or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection, have agreed to continue adequate contraception or abstinence through 3 months following the second injection (Phase 2 part) or following the third vaccination (Phase 3 part), are not currently breastfeeding. Exclusion Criteria: Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration. History of allergy to any component of the vaccine or its excipients. Prior history of allergic or anaphylactic reaction after previous dose of a meningococcal capsular 12 polysaccharide-, diphtheria toxoid- or CRM197-containing vaccine, or to any component of Menactra. Significant infection (e.g., positive SARS-CoV-2 RT-PCR) or other acute illness, including fever >100.4 °F (>38.0 °C) within 2 weeks prior to administration of vaccine. A medical or psychiatric condition that, according to the investigator's judgment, may pose additional risk as a result of participation, interfere with study assessments, interfere with interpretation of results or compromise participant safety. Participants with history of multisystemic-inflammatory syndrome in children (MIS-C). Participated in an interventional clinical study within 28 days prior to Day 1. Received any non-study vaccine within 28 days before or after any dose of vaccine (except for seasonal influenza vaccine, which is permitted within 14 days before or after any dose of vaccine). Thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection. Severe and uncontrolled ongoing autoimmune or inflammatory disease, history of Guillain-Barre syndrome, or any other demyelinating condition Prior/concomitant therapy: Receipt of immunoglobulin or another blood product within the 3 months before expected day of randomization (Visit 1) in this study or those who expect to receive immunoglobulin or another blood product during this study, Immunosuppressive treatment during the course of the study (unless such treatment has to be administered in an emergency situation). Note: Specifically, treatment that can be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled (>800 μg/day of beclomethasone dipropionate or equivalent) corticosteroids, radiation treatment or other immunosuppressive or cytotoxic drugs. Use of inhaled (low dose), intranasal or topical steroids is permitted Glucocorticoids at a dose ≥20 mg/day of prednisone or equivalent given daily or on alternate days for ≥14 consecutive days between randomization and the participant´s schedule Other systemically administered drugs with significant immunosuppressive activity, such as azathioprine, tacrolimus, cyclosporine, methotrexate, or cytotoxic chemotherapy between randomization and the participant´s schedule Prior administration of an investigational or approved CoV vaccine (such as, SARS-CoV-2, SARS CoV, Middle East Respiratory Syndrome CoV) or planned use during the trial. Treatment with investigational or approved agents for prophylaxis against COVID 19 (such as, receipt of SARS-CoV-2 monoclonal antibodies or oral COVID 19 anti-viral agents) within 6 months prior to enrolment. Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1). Others: Any member of the study team or sponsor. An immediate family member or household member of the study's personnel.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential Assignment: st phase: Dose-finding part participants aged ≥5 to <12 years nd phase: Dose-finding part participants aged ≥2 to <5 years rd phase: Confirmatory Part participants aged ≥5 to <12 years th phase: Confirmatory Part participants aged ≥2 to <5 years
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose finding ≥5 to <12 years<br>on Day 1 and Day 29 either VLA2001 half dose or VLA2001 full dose | Biological: VLA2001<br>* whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG)1018 in combination with aluminium hydroxide<br>|
| Experimental: Dose finding ≥2 to <5 years<br>on Day 1 and Day 29 either VLA2001 half dose or VLA2001 full dose | Biological: VLA2001<br>* whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG)1018 in combination with aluminium hydroxide<br>|
| Other: Confirmatory ≥5 to <12 years<br>Day 1: VLA2001 selected dose (= either VLA2001 half dose or VLA2001 full dose) Day 29: VLA2001 selected dose (= either VLA2001 half dose or VLA2001 full dose) Day 57: Active Comparator | Biological: VLA2001<br>* whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG)1018 in combination with aluminium hydroxide<br>Drug: Active Comparator<br>* Menactra, Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine.<br>|
| Other: Confirmatory ≥2 to <5 years<br>Day 1: Active Comparator Day 29: VLA2001 selected dose (= either VLA2001 half dose or VLA2001 full dose) Day 57: VLA2001 selected dose (= either VLA2001 half dose or VLA2001 full dose) | Biological: VLA2001<br>* whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG)1018 in combination with aluminium hydroxide<br>Drug: Active Comparator<br>* Menactra, Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of solicited local and systemic adverse events (AE) |  | up to 7 days after each vaccination | 
| Immune response measured after completion of a 2-dose immunization schedule with VLA2001 as determined by the Geometric Mean Titer (GMT) |  | 2 weeks after completion of a 2-dose immunization schedule | 
| Immune response measured after completion of a 2-dose immunization schedule with VLA2001 as determined by seroconversion rate (SCR) (defined as 4-fold increase from baseline) of SARS-CoV-2-specific neutralising antibodies |  | 2 weeks after completion of a 2-dose immunization schedule | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency, causality and severity of any Adverse Event (AE) | Dose Finding Part | up to Month 12 | 
| Frequency and causality of any serious adverse events (SAEs) | Dose Finding Part | up to Month 12 | 
| Frequency, causality and severity of medically-attended AEs (MAAEs) | Dose Finding Part | up to Month 12 | 
| Frequency, causality and severity of adverse events of special interest (AESIs) | Dose Finding Part | up to Month 12 | 
| Immune response of VLA2001 as determined by the Geometric Mean Titer (GMT) of SARS-CoV-2-specific neutralising antibodies | Dose Finding Part | up to Month 12 | 
| Immune response of VLA2001 as determined by seroconversion rate (SCR) (defined as 4-fold increase from baseline) of SARS-CoV-2-specific neutralising antibodies | Dose Finding Part | up to Month 12 | 
| Immune response of VLA2001 as determined by the Geometric Mean Titer (GMT) of SARS-CoV-2-specific S-protein binding antibodies | Dose Finding Part | up to Month 12 | 
| Immune response of VLA2001 as determined by seroconversion rate (SCR) (defined as 4-fold increase from baseline) of SARS-CoV-2-specific S-protein binding antibodies | Dose Finding Part | up to Month 12 | 
| Frequency and severity of solicited local and systemic adverse events (AEs) | Confirmatory Phase | up to 7 days after each vaccination | 
| Frequency, causality and severity of any unsolicited adverse event (AE) up to 4 weeks following the immunization with VLA2001 (administered as a first dose) in comparison to the vaccination with the comparator vaccine (administered as a first dose) | Confirmatory Phase | up to 4 weeks following immunization | 
| Frequency, causality and severity of any adverse event (AE) | Confirmatory Phase | up to Month 12 | 
| Frequency, causality and severity of participants with medically-attended adverse events (MAAEs) | Confirmatory Phase | up to Month 12 | 
| Frequency and causality of any serious adverse events (SAEs) | Confirmatory Phase | up to Month 24 | 
| Frequency, causality and severity of adverse events of special interest (AESIs) including multisystem inflammatory syndrome in children (MISC) | Confirmatory Phase | up to Month 24 | 
| Immune response of VLA2001 as determined by the Geometric Mean Titer (GMT) of SARS-CoV-2-specific neutralising antibodies | Confirmatory Phase | up to Month 12 | 
| Immune response of VLA2001 as determined by seroconversion rate (SCR) (defined as 4-fold increase from baseline) of SARS-CoV-2-specific neutralising antibodies | Confirmatory Phase | up to Month 12 | 
| Immune response of VLA2001 as determined by the Geometric Mean Titer (GMT) of SARS-CoV-2-specific S-protein binding antibodies | Confirmatory Phase | up to Month 12 | 
| Immune response of VLA2001 as determined by seroconversion rate (SCR) (defined as 4-fold increase from baseline) of SARS-CoV-2-specific S-protein binding antibodies | Confirmatory Phase | up to Month 12 | 
| Assessment of T-cell responses from PBMCs in participants after in vitro stimulation with SARS-CoV-2 antigens using e.g. ELISpot or intracellular cytokine staining |  | up to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLA2001, SARS-CoV-2 Infection, COVID-19