Study on an Investigational Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Administered as a 5- and/or 10-year Booster Doses in Children and Adolescents Vaccinated 5 or 10 Years Earlier as Toddlers

Healthy Volunteers Clinical Trial

Official title:

A Phase IIIb, Open-label, Multi-center Study to Evaluate the Immunogenicity and Safety of a Booster Dose and Describe the Immune Persistence of MenACYW Conjugate Vaccine With 5- and/or 10-year Booster Doses in Children and Adolescents Who Had Been Primed With MenACYW Conjugate Vaccine as Toddlers.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04936685
• Other study ID #: MEQ00073
• Secondary ID: U1111-1255-49412
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 23, 2022
• Est. completion date: December 26, 2027

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the MEQ00073 study is to assess the immunogenicity and safety of a booster dose in children who had been vaccinated with MenACYW conjugate vaccine approximately 5 years earlier as toddlers as part of the MET51 study, and to describe the persistence of a priming dose in children and adolescents who had been vaccinated with MenACYW conjugate vaccine approximately 5 years or 10 years earlier as toddlers as part of the MET51 study, the immunogenicity and safety of a booster dose in adolescents who had been primed with MenACYW conjugate vaccine as toddlers as part of the MET51 study, and the immunogenicity and safety of a second booster dose in adolescents approximately 5 years after a first booster dose as children approximately 5 years after the priming dose as toddlers.

Description:

The duration of each participant's participation will be approximately 5.5 years

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 209
• Est. completion date: December 26, 2027
• Est. primary completion date: March 9, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 7 Years

Eligibility

Inclusion Criteria:

• Received MenACYW vaccine in MET51 study (Groups 1 and 3) and completed the study (attended Visit 2)

• Participant and parent/ legally acceptable representative (LAR) are able to attend all scheduled visits and to comply with all trial procedures

• Covered by health insurance, if required by local regulations

Exclusion Criteria:

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically

• At high risk for meningococcal infection during the trial (specifically but not limited to participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling to countries with high endemic or epidemic disease)

• Personal history of Guillain-Barré syndrome (GBS)

• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid containing vaccine

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances

• Verbal report by parent or LAR of thrombocytopenia or suspected thrombocytopenia, contraindicating intramuscular (IM) vaccination

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination

• Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (ie, mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, W, or Y) with the exception of licensed MenC vaccination received during infancy (MET51 Group 3), of the single dose of meningococcal vaccine administered as part of study MET51 (Group 1 and 3) and of Meningococcal B vaccine

• Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following trial vaccination except for influenza vaccination, which may be received at least 2 weeks before or after study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines

• Receipt of immune globulins, blood or blood-derived products in the past 3 months

• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw

• Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure

• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion

• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature = 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided

• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily

• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study

• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Healthy Volunteers
• Meningococcal Immunisation

Intervention

Biological:
• Meningococcal Polysaccharide (Serogroups A, C, W, and Y) Tetanus Toxoid Conjugate Vaccine
Liquid solution for injection Intramuscular

Locations

Country	Name	City	State
Finland	Investigational Site Number : 2460009	Espoo
Finland	Investigational Site Number : 2460001	Helsinki
Finland	Investigational Site Number : 2460006	Helsinki
Finland	Investigational Site Number : 2460002	Järvenpää
Finland	Investigational Site Number : 2460004	Kokkola
Finland	Investigational Site Number : 2460007	Oulu
Finland	Investigational Site Number : 2460003	Pori
Finland	Investigational Site Number : 2460008	Tampere
Finland	Investigational Site Number : 2460010	Turku
Germany	Investigational Site Number : 2760011	Bönnigheim
Germany	Investigational Site Number : 2760001	Bramsche
Germany	Investigational Site Number : 2760007	Bretten
Germany	Investigational Site Number : 2760004	Erfurt
Germany	Investigational Site Number : 2760015	Hamburg
Germany	Investigational Site Number : 2760002	Mönchengladbach
Germany	Investigational Site Number : 2760008	Mönchengladbach
Germany	Investigational Site Number : 2760006	Schönau
Germany	Investigational Site Number : 2760003	Tauberbischofsheim
Hungary	Investigational Site Number : 3480001	Budapest
Hungary	Investigational Site Number : 3480002	Budapest
Hungary	Investigational Site Number : 3480005	Miskolc
Hungary	Investigational Site Number : 3480006	Székesfehérvár
Spain	Investigational Site Number : 7240001	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240002	Madrid
Spain	Investigational Site Number : 7240006	Santiago de Compostela	Galicia [Galicia]
Spain	Investigational Site Number : 7240003	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

Finland,  Germany,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Group 1: Percentage of Participants With Sufficiency of Serum Bactericidal Assay Using Human Complement (hSBA) Vaccine Seroresponse at 30 Days Post Booster Dose	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. hSBA vaccine seroresponse for serogroups A, C, W, and Y is defined as: percentage of participants with a pre-vaccination titer < 1:8, who had achieved a post-vaccination titer >= 1:16 or participants with a pre-vaccination titer >= 1:8, who had achieved a post-vaccination titer at least 4-fold greater than the pre-vaccination titer. The seroresponse sufficiency was demonstrated if the lower limit of 1-sided 97.5% confidence interval (CI) is > 75%.	Baseline (Day 1) and 30 days after the MenACYW conjugate vaccine 5-year booster dose
Secondary	Antibody Persistence of Meningococcal (Groups 1 and 2): Percentage of Participants Achieving Titer (Seroprotection) >=1:8 hSBA and Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Titer >=1:8 Approximately 5 Years After the Primary Vaccination	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA and the rSBA and the results were expressed as vaccine seroprotection. Seroprotection rate is defined as percentage of participants with hSBA titer and rSBA titer >=1.8 who received MenACYW conjugate vaccine 5 years earlier. Antibody persistence of meningococcal serogroups A, C, W, and Y in children at 5 years (Groups 1 and 2).	At Day 1 (approximately 5 year after the administration of a priming dose as toddlers in study MET51)
Secondary	Group 1: Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA and the rSBA and the results were expressed as geometric mean titers.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Geometric Mean Titers Against Meningococcal Serogroups A, C, W, and Y	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA and the rSBA and the results were expressed as geometric mean titers.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Percentage of Participants With hSBA Titer >= 1:4 and >= 1:8	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. hSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:16 for participants with pre-vaccination hSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination hSBA titer >= 1:8.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Percentage of Participants With hSBA Titer >= 1:4 and >= 1:8	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. hSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:16 for participants with pre-vaccination hSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination hSBA titer >= 1:8.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Percentage of Participants With rSBA Titer >= 1:8 and >= 1:128	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the rSBA. rSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:32 for participants with pre-vaccination rSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination rSBA titer >= 1:8.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Percentage of Participants With rSBA Titer >= 1:8 and >= 1:128	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the rSBA. rSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:32 for participants with pre-vaccination rSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination rSBA titer >= 1:8.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Percentage of Participants With hSBA Titer >=4-Fold Rise From Pre-Vaccination to Post-Vaccination	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. hSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:16 for participants with pre-vaccination hSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination hSBA titer >= 1:8.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Percentage of Participants With hSBA Titer >=4-Fold Rise From Pre-Vaccination to Post-Vaccination	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the hSBA. hSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:16 for participants with pre-vaccination hSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination hSBA titer >= 1:8.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Percentage of Participants With rSBA Titer >=4-Fold Rise From Pre-Vaccination to Post-Vaccination	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the rSBA. rSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:32 for participants with pre-vaccination rSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination rSBA titer >= 1:8.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Percentage of Participants With rSBA Titer >=4-Fold Rise From Pre-Vaccination to Post-Vaccination	Functional meningococcal antibody activity against serogroups A, C, Y, and W were measured in a serum bactericidal assay utilizing the rSBA. rSBA vaccine seroresponse is defined as a post-vaccination titer >= 1:32 for participants with pre-vaccination rSBA titer < 1:8, or a post-vaccination titer >= 4-fold increase at post baseline for participants with pre-vaccination rSBA titer >= 1:8.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Percentage of Participants With >=0.01 International Units (IU)/mL and >=0.1 IU/mL Anti-Tetanus Antibody Concentration	Anti-tetanus antibodies were measured by diphtheria, tetanus, pertussis multiplexed electrochemiluminescent (DTP-ECL) assay, a multiplexed serological assay that allowed for the simultaneous quantification of human antibodies to 6 specific antigens including diphtheria toxoid, tetanus toxoid, and 4 pertussis antigens: pertussis toxin, filamentous hemagglutinin, fimbriae and pertactin. The captured antibodies were then detected using a sulfotag-conjugated anti-human immunoglobulin (Ig)G conjugate.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Percentage of Participants With >=0.01 International Units (IU)/mL and >=0.1 IU/mL Anti-Tetanus Antibody Concentration	Anti-tetanus antibodies were measured by diphtheria, tetanus, pertussis multiplexed electrochemiluminescent (DTP-ECL) assay, a multiplexed serological assay that allowed for the simultaneous quantification of human antibodies to 6 specific antigens including diphtheria toxoid, tetanus toxoid, and 4 pertussis antigens: pertussis toxin, filamentous hemagglutinin, fimbriae and pertactin. The captured antibodies were then detected using a sulfotag-conjugated anti-human immunoglobulin (Ig)G conjugate.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Geometric Mean Concentrations of Anti-Tetanus Antibody Concentration	Anti-tetanus antibodies were measured by DTP-ECL assay, a multiplexed serological assay that allowed for the simultaneous quantification of human antibodies to 6 specific antigens including diphtheria toxoid, tetanus toxoid, and 4 pertussis antigens: pertussis toxin, filamentous haemagglutinin, fimbriae and pertactin. The captured antibodies were then detected using a sulfotag-conjugated anti-human Ig G conjugate.	Baseline (Day 1) and Day 31 after the administration of a 5-year booster dose
Secondary	Group 2: Geometric Mean Concentrations of Anti-Tetanus Antibody Concentration	Anti-tetanus antibodies were measured by DTP-ECL assay, a multiplexed serological assay that allowed for the simultaneous quantification of human antibodies to 6 specific antigens including diphtheria toxoid, tetanus toxoid, and 4 pertussis antigens: pertussis toxin, filamentous haemagglutinin, fimbriae and pertactin. The captured antibodies were then detected using a sulfotag-conjugated anti-human Ig G conjugate.	From Baseline (Day 1) until end of the study (approximately 5.5 years)
Secondary	Group 1: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions (i.e.pre-listed in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination).	Within 30 minutes after vaccination
Secondary	Group 1: Number of Participants With Solicited Injection Site Reactions and Systemic Reactions	All noxious and unintended responses to a study vaccine related to any dose was considered adverse reactions (AR). A solicited reaction is an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB. An injection/administration site reaction is an AR at and around the injection/administration site. Injection/administration site reactions are commonly inflammatory reactions. They were considered to be related to the study vaccine administered. Systemic reactions were all ARs that were not injection or administration site reactions and included systemic manifestations such as headache, fever, as well as localized or topical manifestations that are not associated with the vaccination or administration site.	7 days after vaccination
Secondary	Group 1: Number of Participants With Unsolicited AEs	An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions (i.e. pre-listed in the CRB in terms of diagnosis and/or onset window post-vaccination). Unsolicited AEs included both serious and non-serious unsolicited AEs.	Within 30 days after vaccination
Secondary	Group 1: Number of Participants With Serious AEs (SAEs) and Adverse Event of Special Interest (AESI)	A SAEs is defined as any untoward medical occurrence, at any dose that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other important medical event. An AESI (serious or non-serious) is defined as one of scientific and medical concern specific to the Sponsor's study vaccination or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate.	From the first study vaccine administration up to primary completion date of 09 March 2023, approximately 28 weeks