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

NCT ID: NCT01424644

Last Updated: 2014-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 801 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-12-31

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.

Conditions

Meningococcal Meningitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine

Intervention Type: BIOLOGICAL

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®.

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.

Group Type: EXPERIMENTAL

MenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine

Intervention Type: BIOLOGICAL

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®.

Interventions

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®.

Intervention Type: 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®.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 11 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Vaccines

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Vaccines

Role: STUDY_CHAIR

Novartis Vaccines

Locations

Birmingham Pediatrics, 806 Saint Vincent's Drive, Suite 615

Birmingham, Alabama, United States

Prairie Fields Family Medicine, 350 W. 23rd Street, Suite A

Fremont, California, United States

Madera Family Medical Group, 1111 W. Fourth Street

Madera, California, United States

Clinical Research Advantage / Colorado Springs Health Partners, 6340 Barnes Road

Colorado Springs, Colorado, United States

Dayton Clinical Research, 1100 Salem Ave

Dayton, Florida, United States

Altamonte Pediatric Associates, 101 N. Country Club Rd. #113

Lake Mary, Florida, United States

Pediatrics and Adolescent Medicine, 2155 Post Oak Tritt Road, Suite 100

Marietta, Georgia, United States

Clinical Research Advantage / Ridge Family Physicians, 201 Ridge Street, Suite 201

Council Bluffs, Iowa, United States

Columbia Medical Practice, 5450 Knoll North Drive, Suite 215

Columbia, Maryland, United States

Roslindale Pediatrics Associates, 1153 Centre Street, Suite 31

Boston, Massachusetts, United States

Bellevue Family Practice, 2206 Longo Suite 201

Bellevue, Nebraska, United States

Complete Children's Health, 8201 Northwoods Drive

Lincoln, Nebraska, United States

Meridian Clinical Research, 3319 North, 107th Street

Omaha, Nebraska, United States

Pediatrics and Adolescent Medicine, 120 Stonebridge Parkway, Suite 410

Woodstock, New York, United States

Capitol Pediatrics and Adolescent Center, 3801 Computer Drive Suite 200

Raleigh, North Carolina, United States

Ohio Pediatric Research Association, 7371 Brandt Pike Suite C

Huber Heights, Ohio, United States

Omega Medical Research, 400 Bald Hill Road

Warwick, Rhode Island, United States

HOSPITAL"SAN MARTINO". Department of Health Sciences University of Genoa

Via Pastore, 1, Genoa, Italy

Hospital "Maggiore della Carità". Pediatric Clinic

Corso Mazzini, 18, Novara, Italy

Hospital of Taranto- Unit of Hygiene and Publich Health Vaccination Center

Viale Magna Grecia, 173, Taranto, Italy

Countries

United States; Italy

References

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.

Reference Type: DERIVED

PMID: 31377946 (View on PubMed)

Other Identifiers

2011-000476-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V59_40

Identifier Type: -

Identifier Source: org_study_id