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

A Phase II Study of the Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adolescents

The purpose of the study was to evaluate the immunogenicity and describe the safety of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed vaccine MENVEO® in adolescents 10 to 17 years of age in the United States (US). This study also evaluated the immunogenicity and safety of MenACYW Conjugate vaccine when given alone compared to when given concomitantly with tetanus, diphtheria, acellular pertussis (Tdap) vaccine and human papilloma virus (HPV) vaccine.

Primary objective:

• To evaluate the antibody responses to the antigens present in MenACYW Conjugate vaccine when MenACYW Conjugate vaccine was given alone compared to those when MENVEO vaccine was given alone.

Secondary objective:

• To evaluate the antibody responses to the antigens present in MenACYW Conjugate vaccine, when MenACYW Conjugate vaccine was given concomitantly with Tdap and HPV vaccines, compared to those when it was given alone.
• To evaluate the antibody responses to the antigens present in Tdap vaccine, when Tdap vaccine was given concomitantly with MenACYW Conjugate vaccine and HPV vaccine, compared to those when Tdap vaccine was given with HPV vaccine only.
• To evaluate the antibody responses to the antigens present in HPV vaccine after the 3-dose series, when the first dose of HPV vaccine is given concomitantly with MenACYW Conjugate vaccine and Tdap vaccine, compared to those when the first dose of HPV vaccine is given with Tdap vaccine only.

Observational objective:

• To describe the safety profile of MenACYW Conjugate vaccine, compared to that of the licensed vaccine MENVEO®, and when MenACYW Conjugate vaccine was given with Tdap and HPV vaccines.

Study Overview

• Status: Completed
• Conditions: Meningitis; Meningococcal Infections; Meningococcal Meningitis
• Intervention / Treatment: Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine; Biological: Meningococcal (Groups A, C, Y and W135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine; Biological: Adacel®: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed; Biological: GARDASIL®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1715
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
    • Huntsville, Alabama, United States, 35802
  • California
    • Downey, California, United States, 90241
    • San Diego, California, United States, 92103
  • Florida
    • Miami Beach, Florida, United States, 33141
  • Kansas
    • Wichita, Kansas, United States, 67205
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
    • Nicholasville, Kentucky, United States, 40356
  • Maryland
    • Columbia, Maryland, United States, 21075
  • Nebraska
    • Lincoln, Nebraska, United States, 68504
    • Lincoln, Nebraska, United States, 68505
    • Lincoln, Nebraska, United States, 68516
  • Ohio
    • Cleveland, Ohio, United States, 44121
    • Dayton, Ohio, United States, 45414
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
  • South Carolina
    • Charleston, South Carolina, United States, 29414
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
    • Tullahoma, Tennessee, United States, 37388
  • Utah
    • Layton, Utah, United States, 84041
    • Orem, Utah, United States, 84057
    • Payson, Utah, United States, 84651
    • Provo, Utah, United States, 84064
    • Roy, Utah, United States, 84067
    • Salt Lake City, Utah, United States, 84109
    • Salt Lake City, Utah, United States, 84124
    • South Jordan, Utah, United States, 84095
    • Spanish Fork, Utah, United States, 84660
    • Syracuse, Utah, United States, 84075
    • West Haven, Utah, United States, 84401
    • West Jordan, Utah, United States, 84088
  • Virginia
    • Charlottesville, Virginia, United States, 22902
    • Midlothian, Virginia, United States, 23113
  • Washington
    • Spokane, Washington, United States, 99204
    • Spokane, Washington, United States, 99218

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: MenACYW Conjugate Vaccine; Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular (IM); Other Names: MenACYW Conjugate vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular (IM); Other Names: MenACYW Conjugate vaccine
Active Comparator: Group 2: MENVEO® Vaccine; Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of MENVEO® vaccine on Day 0.	Biological: Meningococcal (Groups A, C, Y and W135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine; 0.5 mL, IM; Other Names: MENVEO®
Experimental: Group 3: MenACYW Conjugate Vaccine+Tdap+HPV; Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of MenACYW Conjugate vaccine, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap), and Dose 1 of HPV Vaccine on Day 0. HPV Vaccine Dose 2 and Dose 3 were given at 2 and 6 months, respectively, after Dose 1 given on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular (IM); Other Names: MenACYW Conjugate vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular (IM); Other Names: MenACYW Conjugate vaccine; Biological: Adacel®: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed; 0.5 mL, IM; Other Names: Adacel® (Tdap); Biological: GARDASIL®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant; 0.5 mL, IM; Other Names: GARDASIL® (HPV)
Active Comparator: Group 4: Tdap+HPV; Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of Tdap and Dose 1 of HPV Vaccine on Day 0. HPV Vaccine Dose 2 and Dose 3 were given at 2 and 6 months, respectively, after Dose 1 given on Day 0.	Biological: Adacel®: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed; 0.5 mL, IM; Other Names: Adacel® (Tdap); Biological: GARDASIL®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant; 0.5 mL, IM; Other Names: GARDASIL® (HPV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Day 30 (post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Day 30 (post-vaccination on Day 0)
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	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).	Day 30 (post-vaccination on Day 0)
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	Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-Tetanus antibodies were measured by ELISA.	Day 30 (post-vaccination on Day 0)
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	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.	Day 210 (post-vaccination on Day 0)
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	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.	Within 7 days after vaccines injections at Day 0
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	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.	Within 7 days after vaccines injections at Day 0
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4	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.	Within 7 days after vaccines injections at Day 0

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2014
• Primary Completion (Actual): October 2, 2015
• Study Completion (Actual): October 2, 2015

Study Registration Dates

• First Submitted: July 23, 2014
• First Submitted That Met QC Criteria: July 23, 2014
• First Posted (Estimate): July 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Meningitis; Meningococcal Meningitis; MenACYW Conjugate vaccine; MENVEO vaccine; Adacel®; GARDASIL®
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: MET50; U1111-1143-8537 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No