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

Primary Purpose

Meningococcal Meningitis

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Placebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
MenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Meningococcal Meningitis focused on measuring meningitis, human papillomavirus, tetanus, diptheria, pertussis

Eligibility Criteria

11 Years - 18 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Birmingham Pediatrics, 806 Saint Vincent's Drive, Suite 615
  • Prairie Fields Family Medicine, 350 W. 23rd Street, Suite A
  • Madera Family Medical Group, 1111 W. Fourth Street
  • Clinical Research Advantage / Colorado Springs Health Partners, 6340 Barnes Road
  • Dayton Clinical Research, 1100 Salem Ave
  • Altamonte Pediatric Associates, 101 N. Country Club Rd. #113
  • Pediatrics and Adolescent Medicine, 2155 Post Oak Tritt Road, Suite 100
  • Clinical Research Advantage / Ridge Family Physicians, 201 Ridge Street, Suite 201
  • Columbia Medical Practice, 5450 Knoll North Drive, Suite 215
  • Roslindale Pediatrics Associates, 1153 Centre Street, Suite 31
  • Bellevue Family Practice, 2206 Longo Suite 201
  • Complete Children's Health, 8201 Northwoods Drive
  • Meridian Clinical Research, 3319 North, 107th Street
  • Pediatrics and Adolescent Medicine, 120 Stonebridge Parkway, Suite 410
  • Capitol Pediatrics and Adolescent Center, 3801 Computer Drive Suite 200
  • Ohio Pediatric Research Association, 7371 Brandt Pike Suite C
  • Omega Medical Research, 400 Bald Hill Road
  • HOSPITAL"SAN MARTINO". Department of Health Sciences University of Genoa
  • Hospital "Maggiore della Carità". Pediatric Clinic
  • Hospital of Taranto- Unit of Hygiene and Publich Health Vaccination Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo + Tdap + HPV

MenACWY-CRM + Tdap + HPV

Arm Description

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.

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.

Outcomes

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
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
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.
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
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
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.

Full Information

First Posted
August 23, 2011
Last Updated
January 21, 2014
Sponsor
Novartis
Collaborators
Novartis Vaccines
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1. Study Identification

Unique Protocol Identification Number
NCT01424644
Brief Title
A Phase 4, Placebo-Controlled, Randomized Study to Evaluate the Immunogenicity and Safety of HPV and Tdap When Administered With MenACWY in Adolescents
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis
Collaborators
Novartis Vaccines

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningococcal Meningitis
Keywords
meningitis, human papillomavirus, tetanus, diptheria, pertussis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
801 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo + Tdap + HPV
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
MenACWY-CRM + Tdap + HPV
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Placebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
Intervention Description
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®.
Intervention Type
Biological
Intervention Name(s)
MenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
Intervention Description
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®.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
1 month post Tdap vaccination.
Title
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
Description
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.
Time Frame
1 month post Tdap vaccination.
Secondary Outcome Measure Information:
Title
Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination.
Description
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.
Time Frame
1 month post MenACWY-CRM vaccination.
Title
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
Description
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.
Time Frame
Day 1-7 after any vaccination.
Title
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
Description
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.
Time Frame
Throughout the study (Day 1 to Day 211).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
11 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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: 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 Had been properly vaccinated against diphtheria, tetanus, and pertussis per local regulations; 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. For female subjects, who had a negative urine pregnancy test. 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: Who were unwilling to give their written assent / consent Who were breastfeeding Who was, and/or whose parents or legal guardians were perceived to be unreliable or unavailable for the duration of the study period Who had previous confirmed or suspected disease caused by N. meningitidis Who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment 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) Who had received prior human papillomavirus (HPV) vaccine 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 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) 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 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) Who had epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome Who had a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including latex allergy 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 Who were known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time; Who have Down's syndrome or other known cytogenic disorders; Who and/or whose families were planning to leave the area of the study site before the end of the study period; Who had any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives. Who were relatives of the study personnel.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines
Organizational Affiliation
Novartis Vaccines
Official's Role
Study Chair
Facility Information:
Facility Name
Birmingham Pediatrics, 806 Saint Vincent's Drive, Suite 615
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
Prairie Fields Family Medicine, 350 W. 23rd Street, Suite A
City
Fremont
State/Province
California
ZIP/Postal Code
68025
Country
United States
Facility Name
Madera Family Medical Group, 1111 W. Fourth Street
City
Madera
State/Province
California
ZIP/Postal Code
93637
Country
United States
Facility Name
Clinical Research Advantage / Colorado Springs Health Partners, 6340 Barnes Road
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80922
Country
United States
Facility Name
Dayton Clinical Research, 1100 Salem Ave
City
Dayton
State/Province
Florida
ZIP/Postal Code
45406
Country
United States
Facility Name
Altamonte Pediatric Associates, 101 N. Country Club Rd. #113
City
Lake Mary
State/Province
Florida
ZIP/Postal Code
32746
Country
United States
Facility Name
Pediatrics and Adolescent Medicine, 2155 Post Oak Tritt Road, Suite 100
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30062
Country
United States
Facility Name
Clinical Research Advantage / Ridge Family Physicians, 201 Ridge Street, Suite 201
City
Council Bluffs
State/Province
Iowa
ZIP/Postal Code
51503
Country
United States
Facility Name
Columbia Medical Practice, 5450 Knoll North Drive, Suite 215
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21045
Country
United States
Facility Name
Roslindale Pediatrics Associates, 1153 Centre Street, Suite 31
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02130
Country
United States
Facility Name
Bellevue Family Practice, 2206 Longo Suite 201
City
Bellevue
State/Province
Nebraska
ZIP/Postal Code
68005
Country
United States
Facility Name
Complete Children's Health, 8201 Northwoods Drive
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68505
Country
United States
Facility Name
Meridian Clinical Research, 3319 North, 107th Street
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68134
Country
United States
Facility Name
Pediatrics and Adolescent Medicine, 120 Stonebridge Parkway, Suite 410
City
Woodstock
State/Province
New York
ZIP/Postal Code
30189
Country
United States
Facility Name
Capitol Pediatrics and Adolescent Center, 3801 Computer Drive Suite 200
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
Facility Name
Ohio Pediatric Research Association, 7371 Brandt Pike Suite C
City
Huber Heights
State/Province
Ohio
ZIP/Postal Code
45424
Country
United States
Facility Name
Omega Medical Research, 400 Bald Hill Road
City
Warwick
State/Province
Rhode Island
ZIP/Postal Code
02886
Country
United States
Facility Name
HOSPITAL"SAN MARTINO". Department of Health Sciences University of Genoa
City
Via Pastore, 1
State/Province
Genoa
ZIP/Postal Code
16132
Country
Italy
Facility Name
Hospital "Maggiore della Carità". Pediatric Clinic
City
Corso Mazzini, 18
State/Province
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Hospital of Taranto- Unit of Hygiene and Publich Health Vaccination Center
City
Viale Magna Grecia, 173
State/Province
Taranto
ZIP/Postal Code
74016
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
31377946
Citation
Miao Y, Mzolo T, Pellegrini M. Immunogenicity of a Quadrivalent Human Papillomavirus Vaccine When Co-Administered with Tetanus-Reduced Diphtheria-Acellular Pertussis and Quadrivalent Meningococcal Conjugate Vaccines in Healthy Adolescents: Results from a Randomized, Observer-Blind, Controlled Trial. Infect Dis Ther. 2019 Sep;8(3):335-341. doi: 10.1007/s40121-019-00258-5. Epub 2019 Aug 3.
Results Reference
derived

Learn more about this trial

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

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