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

NCT01424644 | Completed Phase 4 Results

• 2 other identifiers: V59_402011-000476-34
• Study Type: interventional
• Target: 801
• Locations: 2 countries
• Sites: 20

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

Keywords

meningitis; human papillomavirus; tetanus; diptheria; pertussis

Outcome Measures

Primary Outcomes (2)

• 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.

  1 month post Tdap vaccination.

• 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.

  1 month post Tdap vaccination.

Secondary Outcomes (3)

• Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination.

  1 month post MenACWY-CRM 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

  Day 1-7 after any vaccination.

• 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

  Throughout the study (Day 1 to Day 211).

Study Arms (2)

Placebo + Tdap + HPV

PLACEBO COMPARATOR

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

MenACWY-CRM + Tdap + HPV

EXPERIMENTAL

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

Interventions

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

Placebo + Tdap + HPV

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

MenACWY-CRM + Tdap + HPV

Eligibility Criteria

• Age: 11 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead
• Novartis Vaccines: collaborator

Study Sites (20)

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

Birmingham, Alabama, 35205, United States

Location

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

Fremont, California, 68025, United States

Location

Madera Family Medical Group, 1111 W. Fourth Street

Madera, California, 93637, United States

Location

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

Colorado Springs, Colorado, 80922, United States

Location

Dayton Clinical Research, 1100 Salem Ave

Dayton, Florida, 45406, United States

Location

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

Lake Mary, Florida, 32746, United States

Location

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

Marietta, Georgia, 30062, United States

Location

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

Council Bluffs, Iowa, 51503, United States

Location

Columbia Medical Practice, 5450 Knoll North Drive, Suite 215

Columbia, Maryland, 21045, United States

Location

Roslindale Pediatrics Associates, 1153 Centre Street, Suite 31

Boston, Massachusetts, 02130, United States

Location

Bellevue Family Practice, 2206 Longo Suite 201

Bellevue, Nebraska, 68005, United States

Location

Complete Children's Health, 8201 Northwoods Drive

Lincoln, Nebraska, 68505, United States

Location

Meridian Clinical Research, 3319 North, 107th Street

Omaha, Nebraska, 68134, United States

Location

Pediatrics and Adolescent Medicine, 120 Stonebridge Parkway, Suite 410

Woodstock, New York, 30189, United States

Location

Capitol Pediatrics and Adolescent Center, 3801 Computer Drive Suite 200

Raleigh, North Carolina, 27609, United States

Location

Ohio Pediatric Research Association, 7371 Brandt Pike Suite C

Huber Heights, Ohio, 45424, United States

Location

Omega Medical Research, 400 Bald Hill Road

Warwick, Rhode Island, 02886, United States

Location

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

Via Pastore, 1, Genoa, 16132, Italy

Location

Hospital "Maggiore della Carità". Pediatric Clinic

Corso Mazzini, 18, Novara, 28100, Italy

Location

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

Viale Magna Grecia, 173, Taranto, 74016, Italy

Location

Related Publications (1)

• 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.

  PMID: 31377946 DERIVED

MeSH Terms

Conditions

Meningitis, Meningococcal; Meningitis; Tetanus; Whooping Cough

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Clostridium Infections; Gram-Positive Bacterial Infections; Bordetella Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Posting Director
• Organization: Novartis Vaccines and Diagnostics

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines

  Novartis Vaccines

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2011
• First Posted: August 29, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 14, 2014
• Results First Posted: February 14, 2014

Record last verified: 2014-01

Locations

US (17); IT (3)