Immune Lot Consistency, Immunogenicity, and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine

Meningitis Clinical Trial

Official title:

Immune Lot Consistency, Immunogenicity, and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adolescents and Adults Aged 10 to 55 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02842853
• Other study ID #: MET43
• Secondary ID: U1111-1161-3060
• Status: Completed
• Phase: Phase 3
• Start date: July 15, 2016
• Est. completion date: February 28, 2017

Study information

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

Clinical Trial Summary

The purpose of the study was to evaluate immune lot consistency of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine and the immune non-inferiority compared to the licensed vaccine Menactra®, and describe the safety and additional immunogenicity of these study vaccines in adolescents and adults 10 to 55 years of age in the United States (US).

Primary Objectives:

• To demonstrate the immune lot consistency of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine with respect to serum bactericidal assay using human complement (hSBA) geometric mean titers (GMTs).

• To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine (pooled Lots 1 to 3) compared to those observed following the administration of a single dose of Menactra®.

Secondary Objective:

• To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine (pooled Lots 1 to 3) compared to those observed following the administration of a single dose of Menactra® in the adult population (18 to 55 years old).

• To demonstrate the non-inferiority of the antibody responses to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine (pooled Lots 1 to 3) compared to those observed following the administration of a single dose of Menactra® in the adolescent population (10 to 17 years old).

• To compare the hSBA vaccine seroresponses of meningococcal serogroups A, C, Y, and W for each of 3 lots of MenACYW Conjugate vaccine 30 days (+14 days) after vaccination.

• To compare the hSBA antibody GMTs of meningococcal serogroups A, C, Y, and W following the administration of MenACYW Conjugate vaccine to those observed following the administration of Menactra®.

Observational Objectives:

• To describe the safety profile of MenACYW Conjugate vaccine and that of the licensed Menactra®.

Description:

Healthy meningococcal-vaccine naïve adolescents and adults were randomized and received a single dose of either MenACYW Conjugate vaccine from 1 of the 3 lots (Lot 1, Lot 2, or Lot 3) or Menactra®. They were assessed for immunogenicity at baseline (pre-vaccination) and at 30 to 44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3344
• Est. completion date: February 28, 2017
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 55 Years

Eligibility

Inclusion Criteria:

• Aged 10 to 55 years on the day of inclusion.

• Informed consent form was signed and dated by the participant (aged 18 to 55 years) or assent form was signed and dated by the participant and informed consent form was signed and dated by the parent(s) or guardian (for participants aged 10 to < 18 years).

• Participant (>= 18 years) or participant (10 to < 18 years) and parent / guardian were able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must have been pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination).

• 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 may be received at least 2 weeks before or after the study investigational vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.

• 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).

• 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 vaccines used in the trial or to a vaccine containing any of the same substances.

• Verbal report of thrombocytopenia, as reported by the participant or the participant's parent / guardian, contraindicating intramuscular vaccination in the Investigator's opinion.

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

• Personal history of Guillain-Barre syndrome.

• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within 10 years of the proposed study vaccination.

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

• Current alcohol abuse or drug addiction.

• 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 >= 100.4 degree Fahrenheit [°F]). A prospective participant was not be included in the study until the condition was 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 an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal
• Meningococcal Infections
• Meningococcal Meningitis

Intervention

Biological:
• Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine
0.5 mL, Intramuscular
• Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine
0.5 mL, Intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Titers (GMTs) of Meningococcal Serogroups A, C, Y, And W Antibodies Following Vaccination With 3 Lots of MenACYW Conjugate Vaccine	Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by serum bactericidal assay using human complement (hSBA). Data for this outcome measure were not planned to be collected and analyzed for the Menactra® reporting group.	Day 30 (post-vaccination)
Primary	Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >= 1:16 for participants with pre-vaccination hSBA titers < 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >= 1:8.	Day 30 (post-vaccination)
Secondary	Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine in Adults	Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >= 1:16 for participants with pre-vaccination hSBA titers < 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >= 1:8. Only adults aged 18-55 years who received a single dose of Menactra® (Group 4b) or MenACYW Conjugate vaccine (Group 1b-3b) from any of the lots 1, 2 or 3, were included in this outcome measure.	Day 30 (post-vaccination)
Secondary	Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine in Adolescents	Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >= 1:16 for participants with pre-vaccination hSBA titers < 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >= 1:8. Only adolescents aged 10-17 years who received a single dose of Menactra® (Group 4a) or MenACYW Conjugate vaccine (Group 1a-3a) from any of the lots 1, 2 or 3, were included in this outcome measure.	Day 30 (post-vaccination)
Secondary	Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y And W Following Vaccination With 3 Lots of MenACYW Conjugate Vaccine	Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >= 1:16 for participants with pre-vaccination hSBA titers < 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >= 1:8.	Day 30 (post-vaccination)
Secondary	Geometric Mean Titers (GMTs) of Meningococcal Serogroups A, C, Y, and W Antibodies Following Vaccination With MenACYW Conjugate and Menactra®	Antibody titers of meningococcal serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)