Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adolescents

Healthy adolescents were randomized and received a single dose of their assigned vaccines. They were assessed for immunogenicity at baseline (pre-vaccination) and at 30 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

• Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine (Biological), also known as MenACYW Conjugate vaccine: 0.5 milliliter (mL), Intramuscular (IM)
• Meningococcal (Groups A, C, Y and W135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (Biological), also known as MENVEO®: 0.5 mL, IM
• Adacel®: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Biological), also known as Adacel® (Tdap): 0.5 mL, IM
• GARDASIL®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant (Biological), also known as GARDASIL® (HPV): 0.5 mL, IM
• Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine (Biological), also known as MenACYW Conjugate vaccine: 0.5 mL, Intramuscular (IM)
• Adacel®: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Biological), also known as Adacel® (Tdap): 0.5 mL, IM
• GARDASIL®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant (Biological), also known as GARDASIL® (HPV): 0.5 mL, IM

Primary outcomes

• Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine [Day 30 (post-vaccination)]: 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 greater than or equal to (>=) 1:8 for participants with pre-vaccination hSBA titers less than (<) 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. Data for this outcome measure was not planned to be collected and analyzed for Group 4:Tdap+HPV.

Secondary outcomes

• Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines [Day 30 (post-vaccination on Day 0)]: 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 >= 1:8 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.
• Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines [Day 30 (post-vaccination on Day 0)]: Anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN), and Fimbriae types 2 and 3 (FIM) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
• Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines [Day 30 (post-vaccination on Day 0)]: Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-Tetanus antibodies were measured by ELISA.
• Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines [Day 210 (post-vaccination on Day 0)]: Anti-HPV 6, 11, 16, and 18 antibodies were measured using a competitive Luminex immunoassay. Seroconversion was defined as changing serostatus from seronegative to seropositive. Cutoff values for HPV seropositivity were >= 20 milli-Merck units per milliliter (mMU/mL) for types 6 and 16, >= 16 mMU/mL for type 11, and >= 24mMU/mL for type 18.
• Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 [Within 7 days after vaccines injections at Day 0]: A Solicited Reaction (SR) was an Adverse Event (AE) that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling.
• Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 [Within 7 days after vaccines injections at Day 0]: A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling.
• Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 [Within 7 days after vaccines injections at Day 0]: A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling.

Sex: All, ages: 10 Years to 17 Years, accepts healthy volunteers

Inclusion Criteria:

* Aged 10 to 17 years on the day of inclusion.
* Informed consent form was signed and dated by the parent(s) or another legally acceptable representative.
* Assent form was signed and dated by the participant.
* Participant and parent legally acceptable representative 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 be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination).
* Participation in the 4 weeks preceding the first trial vaccination(s) 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 preceding the first trial vaccination(s) or planned receipt of any vaccine in the 4 weeks prior to or following any trial vaccination except for influenza vaccination, which may be received at least 2 weeks before or after any study vaccines. This exception included monovalent influenza vaccines and multivalent influenza vaccines.
* Previous vaccination against meningococcal disease with either the trial vaccine or any mono- or polyvalent polysaccharide or conjugate meningococcal vaccine containing A, C, W, or Y antigens.
* History of vaccination with any tetanus, diphtheria, or pertussis vaccine within the previous 4 years.
* Previous human papilloma virus (HPV) vaccination.
* 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 (i.e., participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling 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, including encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous pertussis antigen-containing vaccine.
* Personal history of Guillain-Barré syndrome.
* Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within at least 10 years of the proposed study vaccination.
* Verbal report of thrombocytopenia, contraindicating intramuscular vaccination.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular 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 (e.g., human immunodeficiency virus \[HIV\] hepatitis B, hepatitis C) 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 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 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., natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Participant flow

Outcome results

• Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine 75.6 (71.4 to 79.4); Group 2: MENVEO® Vaccine 66.4 (61.9 to 70.7)
• Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines (Secondary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine 75.6; Group 3: MenACYW Conjugate Vaccine+Tdap+HPV 80.6
• Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines (Secondary), Geometric mean, ELISA units (EU)/mL: Group 3: MenACYW Conjugate Vaccine+Tdap+HPV 37.5 (33.8 to 41.7); Group 4: Tdap+HPV 44.4 (39.5 to 49.9)
• Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines (Secondary), Number, percentage of participants: Group 3: MenACYW Conjugate Vaccine+Tdap+HPV 97.8 (95.7 to 99.0); Group 4: Tdap+HPV 98.9 (96.7 to 99.8)
• Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines (Secondary), Number, percentage of participants: Group 3: MenACYW Conjugate Vaccine+Tdap+HPV 97.5 (94.7 to 99.1); Group 4: Tdap+HPV 95.7 (91.4 to 98.3)
• Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 (Secondary), Count of participants, Participants: Group 1: MenACYW Conjugate Vaccine 224; Group 2: MENVEO® Vaccine 209
• Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 (Secondary), Count of participants, Participants: Group 3: MenACYW Conjugate Vaccine+Tdap+HPV 183
• Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 (Secondary), Count of participants, Participants: Group 4: Tdap+HPV 211

Adverse events

Time frame: Adverse event (AE) data were collected from Day 0 (post-vaccination) up to 30 days after last vaccination. SR data were collected within 7 days after any vaccination. Serious adverse events (SAEs) data were collected throughout the study (up to 180 days after vaccination for Group 1 and 2, and up to 210 days after vaccination on Day 0 for Group 3 and 4).

Serious adverse events by term

Other adverse events by term

• Results publication: Chang LJ, Hedrick J, Christensen S, Pan J, Jordanov E, Dhingra MS. A Phase II, randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine, MenACYW-TT, in healthy adolescents in the United States. Vaccine. 2020 Apr 23;38(19):3560-3569. doi: 10.1016/j.vaccine.2020.03.017. Epub 2020 Mar 21. PMID 32209248

• Medical Director, Study director, Sanofi Pasteur Inc.