A Phase 4, Placebo-Controlled, Randomized Study to Evaluate the Immunogenicity and Safety of HPV and Tdap When Administered With MenACWY in Adolescents

• Number of Participants With Antibody levels ≥ 1.0 IU/mL Against Diphtheria (i.e., Seroprotection Rates)One Month Following Vaccination with Tdap Administered Concomitantly with MenACWY and HPV vaccines or concomitantly with Placebo and HPV [ Time Frame: 30 days post first vaccination ] [ Designated as safety issue: No ]
• Number of Participants With Antibody levels ≥ 1.0 IU/mL against Tetanus(i.e., Seroprotection Rates)One Month Following Vaccination with Tdap Administered Concomitantly with MenACWY and HPV or Concomitantly with Placebo and HPV [ Time Frame: 30 days post first vaccination ] [ Designated as safety issue: No ]
• Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigen Filamentous Hemagglutinin (FHA) One Month Following Vaccination with Tdap [ Time Frame: 30 days post first vaccination ] [ Designated as safety issue: No ]
• GMCs of Antibodies Against Pertussis Toxoid (PT) One Month Following Vaccination with Tdap [ Time Frame: 30 days post first vaccination ] [ Designated as safety issue: No ]
• GMCs of Antibodies Against Pertussis Antigen Pertactin (PRN) One Month Following Vaccination with Tdap [ Time Frame: 30 days post first vaccination ] [ Designated as safety issue: No ]
• Number of Participants Who Seroconverted for HPV Type 6 (HPV 6 ≥ 20 mMU/mL) Following the Third HPV Dose [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Number of Participants Who Seroconverted for HPV Type 11 (HPV 11 ≥ 16 mMU/mL) Following the Third HPV Dose [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Number of Participants Who Seroconverted for HPV Type 16 (HPV 16 ≥ 20 mMU/mL) Following the Third HPV Dose [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Number of Participants Who Seroconverted for HPV Type 18 (HPV 18 ≥ 24 mMU/mL) Following the Third HPV Vaccine Dose [ Time Frame: 7 months ] [ Designated as safety issue: No ]
• Frequency and Percentage of Subjects with Post-injection Local or Systemic Reactions, Reported SAEs or Medically Attended AEs [ Time Frame: throughout the study period ] [ Designated as safety issue: Yes ]
  Local and systemic reactions: 7 days post-visit 1. Medically attended AEs: 7 days to 7 months post-visit 1 SAEs: 7 months

• Number of Participants With Seroresponse Against Meningococcal Serogroup A One Month Following MenACWY Administration Concomitantly with Tdap and HPV [ Time Frame: 30 days post visit 1 ] [ Designated as safety issue: No ]
• Number of Participants With Seroresponse Against Meningococcal Serogroup C One Month Following MenACWY Administration Concomitantly with Tdap and HPV [ Time Frame: 30 days post-visit 1 ] [ Designated as safety issue: No ]
• Number of Participants With Seroresponse Against Meningococcal Serogroup W One Month Following MenACWY Administration Concomitantly with Tdap and HPV [ Time Frame: 30 days post-visit 1 ] [ Designated as safety issue: No ]
• Number of Participants With Seroresponse Against Meningococcal Serogroup Y One Month Following MenACWY Administration Concomitantly with Tdap and HPV [ Time Frame: 30 days post-visit 1 ] [ Designated as safety issue: No ]
  Seroresponse is defined ad the antibody titers measured by serum bactericidal assay with human complement (hSBA) prior to the MenACWY vaccination and 30 days after the vaccination.

The main objective of the proposed phase 4 study is to determine whether immune responses to Tdap (GlaxoSmithKline, Boostrix®) and HPV vaccine (Merck & Co., Inc., Gardasil®) when administered concomitantly with MenACWY are comparable to responses elicited by these vaccines when given alone.

• Biological: placebo+ Combined Tetanus, Reduced Diphtheria Toxoid Acellular Pertussis Vaccine+Quadrivalent Human Papillomavirus Vaccine

  All the three vaccines were administered concomittantly. Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine is GARDASIL®.

  Whereas,reduced Diphtheria Toxoid,Acellular Pertussis Vaccine(Tdap) is Boostrix®.

  This group has single diptheria containing vaccine.

• Biological: MenACWY Conjugate Vaccine+Combined Tetanus, Reduced Diphtheria Toxoid,Acellular Pertussis Vaccine +Quadrivalent Human Papillomavirus Vaccine

  All three vaccines were administered concomittantly. MenACWY contains diphtheria toxoid as carrier for the capsular polysaccharides. Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine is GARDASIL®.

  Whereas,reduced Diphtheria Toxoid,Acellular Pertussis Vaccine(Tdap) is Boostrix® This group contains two diphtheria-containing vaccines

• Placebo Comparator: Placebo + Tdap + HPV
  This group will receive Tdap,HPV and placebo concomitantly for the first vaccination.The second and third doses of HPV vaccine will be administered to all subjects 2 and 6 months after the first dose. All subjects will have serum samples collected at Visit 1 (baseline), Visit 2 (31 days) and Visit 5 (30 days post Visit 4) for serology testing.
  Intervention: Biological: placebo+ Combined Tetanus, Reduced Diphtheria Toxoid Acellular Pertussis Vaccine+Quadrivalent Human Papillomavirus Vaccine
• Experimental: Men ACWY +Tdap+HPV
  This group will receive Tdap, HPV and MenACWY concomitantly. The second and third doses of HPV vaccine will be administered to this group on 2 and 6 months after the first dose. All subjects will have serum samples collected at Visit 1 (baseline), Visit 2 (31 days) and Visit 5 (30 days post Visit 4) for serology testing
  Intervention: Biological: MenACWY Conjugate Vaccine+Combined Tetanus, Reduced Diphtheria Toxoid,Acellular Pertussis Vaccine +Quadrivalent Human Papillomavirus Vaccine

Inclusion Criteria:

Individuals eligible for enrollment in this study are female and male subjects who have shown to be healthy and who are:

1. 11-18 years of age inclusive who have given their written consent/assent and if applicable, whose parents or legal guardians have given written informed consent at the time of enrollment;

   • available for all visits and telephone calls scheduled for the study;

   • in good health as determined by:

     • medical history
     • physical assessment
     • clinical judgment of the investigator
2. have been properly vaccinated against diphtheria, tetanus, and pertussis per local regulations;
3. Subjects should be current with childhood DTP-containing vaccinations per local guidelines. Any previous vaccinations containing DTP should be at least 5 years before study enrollment and no prior adolescent vaccinations (11-18 years of age) vaccines containing DTP are allowed.
4. for female subjects, have a negative urine pregnancy test.
5. any female subject who is sexually active must commit to practice appropriate birth control.

Exclusion Criteria:

Individuals not eligible to be enrolled in the study are those:

1. who are unwilling to give their written assent / consent
2. who are breastfeeding
3. who and/or whose parents or legal guardians are perceived to be unreliable or unavailable for the duration of the study period
4. who had a previous confirmed or suspected disease caused by N. meningitidis
5. who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment
6. who have previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational). (Exception: Receipt of OMP-containing Hib vaccines is permitted)
7. who have received prior human papillomavirus (HPV) vaccine
8. who have received investigational agents or vaccines within 30 days prior to enrollment or who expect to receive an investigational agent or vaccine prior to completion of the study

9. who have received live licensed vaccines within 30 days and inactive vaccine within 15 days prior to enrollment or for whom receipt of a licensed vaccine is anticipated during the study period.

   (Exception: Influenza vaccine may be administered up to 15 days prior to each study immunization and no less than 15 days after each study immunization.)

10. who have experienced, within the 7 days prior to enrollment, significant acute or chronic infection (for example requiring systemic antibiotic treatment or antiviral therapy) or have experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment

11. who have any serious acute, chronic or progressive disease such as

    • history of cancer
    • complicated diabetes mellitus
    • advanced arteriosclerotic disease
    • autoimmune disease
    • HIV infection or AIDS
    • blood dyscrasias
    • congestive heart failure
    • renal failure
    • severe malnutrition (Note: Subjects with mild asthma are eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids are not eligible for enrollment)
12. who have epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome
13. who have a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including latex allergy

14. who have a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example):

    • receipt of immunosuppressive therapy within 30 days prior to enrollment (systemic corticosteroids administered for more than 5 days, or in a daily dose > 1 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy)
    • receipt of immunostimulants
    • receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study
15. who are known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
16. who have Down's syndrome or other known cytogenic disorders;
17. who and/or whose families are planning to leave the area of the study site before the end of the study period;
18. who have any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
19. who are relatives of the study personnel.