Clinical trial NCT01424644: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Meningococcal Meningitis
Keywords: meningitis
human papillomavirus
tetanus
diptheria
pertussis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2011-08-29
Enrollment: 801
Sex: ALL
Minimum age (years): 11
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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:

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.

Primary outcomes:
measure: 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
timeFrame: 1 month post Tdap vaccination.
measure: 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
timeFrame: 1 month post Tdap vaccination.
Secondary outcomes:
measure: Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination.
timeFrame: 1 month post MenACWY-CRM vaccination.
measure: 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
timeFrame: Day 1-7 after any vaccination.
measure: 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
timeFrame: Throughout the study (Day 1 to Day 211).
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Pediatrics, 806 Saint Vincent's Drive, Suite 615
state: Alabama
city: Fremont
country: United States
facility: Prairie Fields Family Medicine, 350 W. 23rd Street, Suite A
state: California
city: Madera
country: United States
facility: Madera Family Medical Group, 1111 W. Fourth Street
state: California
city: Colorado Springs
country: United States
facility: Clinical Research Advantage / Colorado Springs Health Partners, 6340 Barnes Road
state: Colorado
city: Dayton
country: United States
facility: Dayton Clinical Research, 1100 Salem Ave
state: Florida
city: Lake Mary
country: United States
facility: Altamonte Pediatric Associates, 101 N. Country Club Rd. #113
state: Florida
city: Marietta
country: United States
facility: Pediatrics and Adolescent Medicine, 2155 Post Oak Tritt Road, Suite 100
state: Georgia
city: Council Bluffs
country: United States
facility: Clinical Research Advantage / Ridge Family Physicians, 201 Ridge Street, Suite 201
state: Iowa
city: Columbia
country: United States
facility: Columbia Medical Practice, 5450 Knoll North Drive, Suite 215
state: Maryland
city: Boston
country: United States
facility: Roslindale Pediatrics Associates, 1153 Centre Street, Suite 31
state: Massachusetts
city: Bellevue
country: United States
facility: Bellevue Family Practice, 2206 Longo Suite 201
state: Nebraska
city: Lincoln
country: United States
facility: Complete Children's Health, 8201 Northwoods Drive
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research, 3319 North, 107th Street
state: Nebraska
city: Woodstock
country: United States
facility: Pediatrics and Adolescent Medicine, 120 Stonebridge Parkway, Suite 410
state: New York
city: Raleigh
country: United States
facility: Capitol Pediatrics and Adolescent Center, 3801 Computer Drive Suite 200
state: North Carolina
city: Huber Heights
country: United States
facility: Ohio Pediatric Research Association, 7371 Brandt Pike Suite C
state: Ohio
city: Warwick
country: United States
facility: Omega Medical Research, 400 Bald Hill Road
state: Rhode Island
city: Via Pastore, 1
country: Italy
facility: HOSPITAL"SAN MARTINO". Department of Health Sciences University of Genoa
state: Genoa
city: Corso Mazzini, 18
country: Italy
facility: Hospital "Maggiore della Carità". Pediatric Clinic
state: Novara
city: Viale Magna Grecia, 173
country: Italy
facility: Hospital of Taranto- Unit of Hygiene and Publich Health Vaccination Center
state: Taranto
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References:
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.