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

Meningitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02199691
• Other study ID #: MET50
• Secondary ID: U1111-1143-8537
• Status: Completed
• Phase: Phase 2
• Start date: July 22, 2014
• Est. completion date: October 2, 2015

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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1715
• Est. completion date: October 2, 2015
• Est. primary completion date: October 2, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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