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

This study has been completed.
Sponsor:
Collaborator:
Novartis Vaccines
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT01424644
First received: August 23, 2011
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

The main objective 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.


Condition Intervention Phase
Meningococcal Meningitis
Biological: Placebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
Biological: MenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 4, Placebo-Controlled, Randomized Study to Evaluate the Immunogenicity and Safety of a Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine (Tdap, Boostrix®) and Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine (Gardasil®) in Healthy Adolescents When Administered With MenACWY Conjugate Vaccine

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo [ Time Frame: 1 month post Tdap vaccination. ] [ Designated as safety issue: No ]
    The percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL (as measured by ELISA) following concomitant administration of Tdap with HPV and MenACWY-CRM vaccine as compared to concomitant administration of Tdap with HPV and placebo.

  • Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo [ Time Frame: 1 month post Tdap vaccination. ] [ Designated as safety issue: No ]
    The geometric mean concentrations (GMCs) of antibodies against pertussis antigens (PT, FHA and PRN), as measured by ELISA, following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.


Secondary Outcome Measures:
  • Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. [ Time Frame: 1 month post MenACWY-CRM vaccination. ] [ Designated as safety issue: No ]
    The immunogenicity was assessed in terms of geometric mean hSBA titers of MenACWY when administered concomitantly with Tdap and HPV at 1 month after 1 dose of MenACWY vaccination.

  • Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo [ Time Frame: Day 1-7 after any vaccination. ] [ Designated as safety issue: Yes ]
    The number of subjects reporting solicited local and systemic reactions following concomitant administration of MenACWY-CRM vaccine, Tdap and HPV vaccine as compared to concomitant administration of placebo with Tdap and HPV.

  • Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo [ Time Frame: Throughout the study (Day 1 to Day 211). ] [ Designated as safety issue: Yes ]

    The number of subjects reporting any unsolicited adverse reactions (AEs) when Tdap and HPV are concomitantly administered with MenACWY-CRM as compared to when Tdap and HPV vaccine are concomitantly administered with placebo.

    Note: A total of 2 MenACWY-CRM+Tdap+HPV subjects reported AEs leading to premature withdrawal - one subject due to treatment emergent AE and another subject prior to study vaccination on day 1.



Enrollment: 801
Study Start Date: September 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 (7 months after visit 1) for serology testing.
Biological: Placebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine

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

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

Experimental: MenACWY-CRM + Tdap + HPV
This group will receive Tdap, HPV and MenACWY-CRM concomitantly. The second and third doses of HPV vaccine will be administered to this group 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 (7 months after visit 1) for serology testing.
Biological: MenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine

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

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


  Eligibility

Ages Eligible for Study:   11 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Individuals eligible for enrollment in this study were female and male individuals who had been shown to be healthy and who were:

  1. 11-18 years of age inclusive who had given their written consent/assent and if applicable, whose parents or legal guardians had 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. Had been properly vaccinated against diphtheria, tetanus, and pertussis per local regulations;
  3. Subjects who were current with childhood DTP-containing vaccinations per local guidelines. Any previous vaccinations containing DTP must have been received at least 5 years before study enrollment and no prior adolescent vaccinations (11-18 years of age) containing DTP vaccines were allowed.
  4. For female subjects, who had a negative urine pregnancy test.
  5. Any female subject who is sexually active committed to practice appropriate birth control.

Exclusion Criteria:

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

  1. Who were unwilling to give their written assent / consent
  2. Who were breastfeeding
  3. Who was, and/or whose parents or legal guardians were perceived to be unreliable or unavailable for the duration of the study period
  4. Who had 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 had previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational). (Exception: Receipt of OMP-containing Hib vaccines was permitted)
  7. Who had received prior human papillomavirus (HPV) vaccine
  8. Who had received investigational agents or vaccines within 30 days prior to enrollment or who expected to receive an investigational agent or vaccine prior to completion of the study
  9. Who had 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 could be administered up to 15 days prior to each study immunization and no less than 15 days after each study vaccination)

  10. Who had experienced, within the 7 days prior to enrollment, significant acute or chronic infection (for example requiring systemic antibiotic treatment or antiviral therapy) or had experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment
  11. Who had 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 were eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids were not eligible for enrollment)
  12. Who had epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome
  13. Who had a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including latex allergy
  14. Who had 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 were 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 were planning to leave the area of the study site before the end of the study period;
  18. Who had any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
  19. Who were relatives of the study personnel.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424644

Locations
United States, Alabama
Birmingham Pediatrics, 806 Saint Vincent's Drive, Suite 615
Birmingham, Alabama, United States, 35205
United States, California
Prairie Fields Family Medicine, 350 W. 23rd Street, Suite A
Fremont, California, United States, 68025
Madera Family Medical Group, 1111 W. Fourth Street
Madera, California, United States, 93637
United States, Colorado
Clinical Research Advantage / Colorado Springs Health Partners, 6340 Barnes Road
Colorado Springs, Colorado, United States, 80922
United States, Florida
Dayton Clinical Research, 1100 Salem Ave
Dayton, Florida, United States, 45406
Altamonte Pediatric Associates, 101 N. Country Club Rd. #113
Lake Mary, Florida, United States, 32746
United States, Georgia
Pediatrics and Adolescent Medicine, 2155 Post Oak Tritt Road, Suite 100
Marietta, Georgia, United States, 30062
United States, Iowa
Clinical Research Advantage / Ridge Family Physicians, 201 Ridge Street, Suite 201
Council Bluffs, Iowa, United States, 51503
United States, Maryland
Columbia Medical Practice, 5450 Knoll North Drive, Suite 215
Columbia, Maryland, United States, 21045
United States, Massachusetts
Roslindale Pediatrics Associates, 1153 Centre Street, Suite 31
Boston, Massachusetts, United States, 02130
United States, Nebraska
Bellevue Family Practice, 2206 Longo Suite 201
Bellevue, Nebraska, United States, 68005
Complete Children's Health, 8201 Northwoods Drive
Lincoln, Nebraska, United States, 68505
Meridian Clinical Research, 3319 North, 107th Street
Omaha, Nebraska, United States, 68134
United States, New York
Pediatrics and Adolescent Medicine, 120 Stonebridge Parkway, Suite 410
Woodstock, New York, United States, 30189
United States, North Carolina
Capitol Pediatrics and Adolescent Center, 3801 Computer Drive Suite 200
Raleigh, North Carolina, United States, 27609
United States, Ohio
Ohio Pediatric Research Association, 7371 Brandt Pike Suite C
Huber Heights, Ohio, United States, 45424
United States, Rhode Island
Omega Medical Research, 400 Bald Hill Road
Warwick, Rhode Island, United States, 02886
Italy
HOSPITAL"SAN MARTINO". Department of Health Sciences University of Genoa
Via Pastore, 1, Genoa, Italy, 16132
Hospital "Maggiore della Carità". Pediatric Clinic
Corso Mazzini, 18, Novara, Italy, 28100
Hospital of Taranto- Unit of Hygiene and Publich Health Vaccination Center
Viale Magna Grecia, 173, Taranto, Italy, 74016
Sponsors and Collaborators
Novartis
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01424644     History of Changes
Other Study ID Numbers: V59_40, 2011-000476-34
Study First Received: August 23, 2011
Results First Received: November 20, 2013
Last Updated: January 21, 2014
Health Authority: United States: Food and Drug Administration
Italy: The Italian Medicines Agency

Keywords provided by Novartis:
meningitis
human papillomavirus
tetanus
diptheria
pertussis

Additional relevant MeSH terms:
Meningitis
Meningitis, Meningococcal
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Bacterial Infections
Meningococcal Infections
Neisseriaceae Infections
Gram-Negative Bacterial Infections

ClinicalTrials.gov processed this record on July 20, 2014