Clinical trial NCT01049035: A Study of a Quadrivalent Meningococcal Tetanus Protein Conjugate Vaccine in Infants and Toddlers
Official title: Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine Administered in Infants and Toddlers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Meningitis
Meningococcal Infection
Keywords: Meningitis
Meningococcal Infection
Neisseria meningitidis
Tetravalent Meningococcal Vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-01-14
Enrollment: 580
Sex: ALL
Minimum age (years): 42
Maximum age (years): 365
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study was to evaluate the optimal vaccination schedule for a Quadrivalent Meningococcal Polysaccharide (A, C, Y and W-135) Tetanus Protein Conjugate Vaccine (MenACYW Conjugate vaccine) in order to provide an effective protein conjugate quadrivalent meningococcal vaccine in the population with the highest incidence of disease.

Objectives:

* To describe the safety profile of MenACYW Conjugate vaccine administered at 5 different schedules and concomitantly with routine pediatric vaccinations.
* To describe the immunogenicity profile of MenACYW Conjugate vaccine administered at 5 different schedules and concomitantly with routine pediatric vaccinations.
* To describe the immunogenicity profiles of selected licensed pediatric vaccines (Pentacel, Prevnar, M-M-RII, and Varivax) when administered either concomitantly with or without MenACYW Conjugate vaccine.

Detailed description: Participants received study vaccinations beginning at age 2, 6, 12, or 15 months, depending on the assigned schedule in their randomized groups. All participants underwent safety and immunogenicity assessments according to the schedule for their assigned group.

Eligibility criteria: Inclusion Criteria:

* Groups 1, 2, 3, 6, and 7: Aged 42 to 89 days on the day of inclusion; Group 4: Aged 6 months (180 days ± 14 days) on the day of inclusion; Group 5: Aged 12 months (365 days + 14 days) on the day of inclusion.
* Born at full term of pregnancy (greater than or equal to \[≥\] 37 weeks) and with a birth weight ≥2.5 kilogram (kg).
* Informed consent form had been signed and dated by the parent or other legally acceptable representative.
* Participant and parent/guardian were able to attend all scheduled visits and to be complied with all trial procedures.
* Group 4 only: Prior receipt of Pentacel and Prevnar at 2 and 4 months; 1 or 2 doses of rotavirus vaccine; and 2 or 3 previous doses of hepatitis B vaccine.

Group 5 only: Prior receipt of Pentacel and Prevnar at 2, 4, and 6 months; 2 or 3 doses of rotavirus vaccine; and 3 previous doses of hepatitis B vaccine.

Exclusion Criteria:

* Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.
* Planned participation in another clinical trial during the present trial period.
* Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
* Planned receipt of any vaccine in the 4 weeks following any trial vaccination, with the exception of influenza vaccine, which may be received 14 days before or after MenACYW Conjugate vaccine.
* Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine.
* Receipt of blood or blood-derived products in the past 30 days, which might interfere with assessment of the immune response.
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks).
* Known personal or maternal seropositivity for human immunodeficiency virus (HIV), hepatitis B vaccine, or hepatitis C, as reported by the parent/guardian.
* History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.
* At high risk for meningococcal infection during the trial.
* 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.
* Thrombocytopenia, as reported by the parent/guardian.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
* History of seizures.
* Personal or family history of Guillain-Barré Syndrome (GBS).
* Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion.

Temporary contraindications were resolved before vaccination:

* Febrile illness (temperature ≥38.0 degree Celsius \[≥100.4 degree Fahrenheit\]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination.
* Group 5 only: Receipt of oral or injected antibiotic therapy within the 72 hours prior to the study blood draw. Topical antibiotics or antibiotic drops were not included in this exclusion criterion. (Note: This did not applied to the other groups at this time, as they did not have a blood draw within 30 days of the initial visit.).

Primary outcomes:
measure: Percentage of Participants With an Serum Bactericidal Assay (SBA) Using Human Complement (SBA-HC) Titer Greater or Than Equal to (≥) 1:8 and ≥1:4: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-protocol Population (PPP)
timeFrame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
measure: Percentage of Participants With an Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
measure: Percentage of Participants With Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Group 5 - Per-Protocol Population
timeFrame: At the age of 13 months
measure: Percentage of Participants With SBA-HC Pre-booster Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC Titer After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Percentage of Participants With SBA-HC Pre-vaccination Titer ≥1:8 Who Then Achieved ≥4-fold Rise in SBA-HC Titer After Vaccination: Group 5 - Per-Protocol Population
timeFrame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
measure: Percentage of Participants With SBA-HC Pre-booster Titer Less Than (<) 1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC After Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Percentage of Participants With SBA-HC Pre-Vaccination Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC Titer After Vaccination: Group 5 - Per-Protocol Population
timeFrame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
measure: Serum Bactericidal Assay Using Human Complement Geometric Mean Titers (GMTs): Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
timeFrame: Groups 1, 2, 4, 6, and 7: at the age of 7 months, Group 3: at the age of 5 months
measure: Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
measure: Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Group 5 - Per-Protocol Population
timeFrame: At the age of 13 months
measure: Percentage of Participants With ≥4-fold Rise in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months), Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Geometric Mean Fold Rise (GMFR) in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3 and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months), Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Percentage of Participants With a Serum Bactericidal Assay Using Baby Rabbit Complement (SBA-BR) Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
timeFrame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
measure: Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
measure: Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Group 5 - Per-Protocol Population
timeFrame: At the age of 13 months
measure: Percentage of Participants With SBA-BR Pre-Booster Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Percentage of Participants With SBA-BR Pre-Vaccination Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Vaccination: Group 5 - Per-Protocol Population
timeFrame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
measure: Percentage of Participants With SBA-BR Pre-Booster Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titers After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Percentage of Participants With SBA-BR Pre-Vaccination Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Vaccination: Group 5 - Per-Protocol Population
timeFrame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
measure: Percentage of Participants With ≥4-fold Rise in SBA-BR Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post booster vaccination (i.e., at the age of 13 months); Group 2: 30 days post booster vaccination (i.e., at the age of 16 months)
measure: Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
timeFrame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
measure: Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, 4, and 6: at the age of 13 months; Group 2 and 7: at the age of 16 months
measure: Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers in Group 5: Per-Protocol Population
timeFrame: At the age of 13 months
measure: Geometric Mean Fold Rise in Serum Bactericidal Assay Using Baby Rabbit Complement Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, and 4: 30 days post booster vaccination at the age of 12 months (i.e., at the age of 13 months); Group 2: 30 days post booster vaccination at the age of 15 months (i.e. at the age of 16 months)
measure: Antibody Titer/Concentration to All the Antigens Contained in Pentacel Vaccines: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population
timeFrame: At the age of 7 months
measure: Antibody Titer/Concentration to All Antigens Contained in Pentacel Vaccines: Groups 2 and 7 - Booster Per-Protocol Population
timeFrame: At the age of 16 months
measure: Percentage of Participants With Antibody Concentration ≥0.35 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population
timeFrame: At the age of 7 months
measure: Percentage of Participants With Antibody Concentration ≥0.35 μg/mL and ≥1.0 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Groups 1, 3, 4, and 6 - Booster Series Per-Protocol Population
timeFrame: At the age of 13 months
measure: Percentage of Participants With Antibody Concentration ≥0.35 μg/mL and ≥1.0 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Group 5- Per-Protocol Population
timeFrame: At the age of 13 months
measure: Percentage of Participants With Antibodies to All Antigens Contained in M-M-RII and VARIVAX Vaccines: Groups 1 and 6 - Booster Per-Protocol Population
timeFrame: At the age of 13 months
measure: Geometric Mean Concentrations (GMCs) of Antibody Titers to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
timeFrame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
measure: Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
timeFrame: Groups 1, 3, 4, and 6: at the age of 13 months, Group 2 and 7: at the age of 16 months
measure: Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Group 5 - Per-Protocol Population
timeFrame: At the age of 13 months
measure: Number of Participants With Solicited Injection Site Reactions
timeFrame: Within 7 days post any vaccination
measure: Number of Participants With Solicited Systemic Reactions
timeFrame: Within 7 days post any vaccination
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Within 30 days post any vaccination
measure: Number of Participants With Immediate Unsolicited AE
timeFrame: Within 30 minutes post any vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Tuscaloosa
country: United States
state: Alabama
city: Jonesboro
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Fountain Valley
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: Marietta
country: United States
state: Georgia
city: Woodstock
country: United States
state: Georgia
city: Bardstown
country: United States
state: Kentucky
city: Crestview Hills
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Bossier City
country: United States
state: Louisiana
city: Clyde
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Pittsburgh
country: United States
state: Pennsylvania
city: Barnwell
country: United States
state: South Carolina
city: Clarksville
country: United States
state: Tennessee
city: Fort Worth
country: United States
state: Texas
city: Layton
country: United States
state: Utah
city: Orem
country: United States
state: Utah
city: Springville
country: United States
state: Utah
city: Midlothian
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Cornish MJ, Hedrick JA, Gabrielsen AA, Johnson AD, Miriam Pina L, Rehm C, Pan J, Neveu D, Da Costa X, Jordanov E, Dhingra MS. Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study. Vaccine. 2022 Mar 1;40(10):1421-1438. doi: 10.1016/j.vaccine.2022.01.050. Epub 2022 Feb 7.