Immunogenicity and Safety of a Booster Dose of a Quadrivalent Meningococcal Conjugate Vaccine in Children

Meningococcal Infections Clinical Trial

Official title:

Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered as a Booster Dose in Children Vaccinated 3 Years Earlier as Toddlers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03476135
• Other study ID #: MET62
• Secondary ID: 2017-001993-40U1
• Status: Completed
• Phase: Phase 3
• Start date: February 27, 2018
• Est. completion date: September 10, 2018

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was an open-label, multi-center study to describe the immune persistence of the priming dose and describe the immunogenicity and safety of a booster dose of Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid (MenACYW) conjugate vaccine in children in Finland who had been vaccinated 3 years earlier as toddlers with either MenACYW conjugate vaccine or Nimenrix® as part of the MET54 study (NCT03205358).

The objectives were:

• To describe the antibody persistence of meningococcal serogroups A, C, Y, and W before a booster dose in children who received either MenACYW conjugate vaccine or Nimenrix® 3 years earlier as toddlers.

• To describe the antibody responses to meningococcal serogroups A, C, Y, and W 30 days after a booster dose of MenACYW conjugate vaccine in children who received either MenACYW conjugate vaccine or Nimenrix® 3 years earlier as toddlers.

• To describe the antibody responses against tetanus toxoid 30 days after a booster dose of MenACYW conjugate vaccine in children who received either MenACYW conjugate vaccine or Nimenrix® 3 years earlier as toddlers.

• To describe the safety profile of a booster dose of MenACYW conjugate vaccine in children who received either MenACYW conjugate vaccine or Nimenrix® 3 years earlier as toddlers.

Description:

Healthy children who were vaccinated 3 years earlier at 12 to 23 months of age in study MET54 (NCT03205358) were eligible for enrollment. All participants received a single booster dose of MenACYW conjugate vaccine on Day 0. Immunogenicity was assessed at pre-vaccination and 30 days after vaccination. Safety was assessed throughout the study period, and included solicited injection site and systemic reactions (Day 0 to Day 7 post-vaccination); unsolicited adverse events up to Day 30 (Visit 2), and serious adverse events occurring throughout the trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: September 10, 2018
• Est. primary completion date: September 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 46 Months to 61 Months

Eligibility

Inclusion Criteria:

• Participated in and completed (attended Visit 2) study MET54.

• Informed consent form had been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness, if required by local regulations).

• Participant and parent/legally acceptable representative were able to attend all scheduled visits and complied with all trial procedures.

• Covered by health insurance where applicable.

Exclusion Criteria:

• Participation 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.

• Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which might be received at a gap of at least 2 weeks before or after the study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines. If the participant was due to receive vaccination(s) recommended for his/her age by the national immunization schedule at the time of the study, the participant was recommended to complete his/her immunization schedule after Visit 2.

• Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B vaccine) with the exception of the single dose of meningococcal vaccine administered as part of study MET54.

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

• 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).

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

• Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the Investigator's opinion.

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

• Personal history of Guillain-Barré syndrome.

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

• Chronic illness that, in the opinion of the Investigator, was 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 degree Celsius [°C]). A prospective participant was not included in the study until the condition had resolved or the febrile event had subsided.

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

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

Related Conditions & MeSH terms

• Meningococcal Infections

Intervention

Biological:
• MenACYW conjugate vaccine
Meningococcal polysaccharide (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine 0.5 mL, intramuscular

Locations

Country	Name	City	State
Finland	Sanofi Pasteur Investigational Site 2460005	Espoo
Finland	Sanofi Pasteur Investigational Site 2460002	Helsinki
Finland	Sanofi Pasteur Investigational Site 2460006	Helsinki
Finland	Sanofi Pasteur Investigational Site 2460007	Järvenpää
Finland	Sanofi Pasteur Investigational Site 2460008	Oulu
Finland	Sanofi Pasteur Investigational Site 2460001	Pori
Finland	Sanofi Pasteur Investigational Site 2460003	Tampere
Finland	Sanofi Pasteur Investigational Site 2460004	Turku

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody Titers Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Before a Booster Dose of MenACYW Conjugate Vaccine in MET62	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA.	Day 0 (pre-vaccination)
Primary	Antibody Titers Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After a Booster Dose of MenACYW Conjugate Vaccine in MET62	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-booster vaccination)
Primary	Antibody Titers Measured by Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Against Meningococcal Serogroups A, C, Y, and W Before a Booster Dose of MenACYW Conjugate Vaccine in MET62	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by rSBA.	Day 0 (pre-vaccination)
Primary	Antibody Titers Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After a Booster Dose of MenACYW Conjugate Vaccine in MET62	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by rSBA.	Day 30 (post-booster vaccination)
Primary	Antibody Titers Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W After Priming Vaccination in MET54 and Booster Vaccination in MET62	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA.	Day 0 (pre-vaccination) and Day 30 (post-priming vaccination) in study MET54, and Day 0 (pre-vaccination) and Day 30 (post-booster vaccination) in study MET62
Primary	Antibody Titers Measured by rSBA Against Meningococcal Serogroups A, C, Y, and W After Priming Vaccination in MET54 and Booster Vaccination in MET62	Antibody titers against meningococcal serogroups A, C, Y, and W were measured by rSBA.	Day 0 (pre-vaccination) and Day 30 (post-priming vaccination) in study MET54, and Day 0 (pre-vaccination) and Day 30 (post-booster vaccination) in study MET62
Primary	Antibody Concentrations Against Tetanus Toxoid Before a Booster Dose of MenACYW Conjugate Vaccine in MET62	Anti-tetanus antibodies were measured by electrochemiluminescent (ECL) assay.	Day 0 (pre-vaccination)
Primary	Antibody Concentrations Against Tetanus Toxoid After a Booster Dose of MenACYW Conjugate Vaccine in MET62	Anti-tetanus antibodies were measured by ECL assay.	Day 30 (post-booster vaccination)
Primary	Number of Participants With Immediate Adverse Event After Vaccination in MET62	Immediate events captured medically relevant unsolicited systemic adverse events (AEs) that occurred within the first 30 minutes after vaccination. An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Systemic AEs were all AEs that were not injection or administration site reactions.	Within 30 minutes after vaccination
Primary	Number of Participants With Solicited Injection Site Reactions and Systemic Reactions in MET62	A solicited reaction (SR) was an adverse reaction (AR) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB. Solicited injection site reactions: pain, erythema, and swelling. Solicited systemic reactions: fever, headache, malaise and, myalgia.	Within 7 days after vaccination
Primary	Number of Participants With Unsolicited Adverse Event After Vaccination in MET62	An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the CRB in terms of diagnosis and/or onset window post-vaccination.	Within 30 days after vaccination
Primary	Number of Participants With a Serious Adverse Event (SAE) After Vaccination in MET62	A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event.	Within 30 days after vaccination