A Study to Evaluate Safety and Immune Response of Novartis Meningococcal ACWY Conjugate Vaccine In Adolescents

A Phase 3, Single-Center, Open-label, Controlled, Randomized Study to Evaluate the Safety and Immunogenicity of Novartis Men ACWY Vaccine Administered Either Alone or Concomitantly With a Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine and Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine in Healthy Adolescents

This study will evaluate the safety and immune response of the Novartis Meningococcal ACWY conjugate vaccine when administered with Tdap and HPV vaccinations to healthy adolescents

Study Overview

• Status: Completed
• Conditions: Pertussis; Tetanus; Human Papillomavirus Infection; Meningococcal Meningitis
• Intervention / Treatment: Biological: Novartis Meningococcal ACWY Conjugate Vaccine; Biological: Tdap Vaccine

• Study Type: Interventional
• Enrollment (Actual): 1620
• Phase: Phase 3

Contacts and Locations

Study Locations

• Costa Rica
  • San Jose, Costa Rica
    • San Jose, Costa Rica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adolescents 11-18 years of age
• virgins (both male and female) with no intention of becoming sexually active during the study period
• who have been properly vaccinated against diphtheria, tetanus, pertussis

Exclusion Criteria:

• who had a previous confirmed or suspected disease caused by N. meningitidis;
• who have previously been immunized with a meningococcal vaccine
• who have received prior human papillomavirus (HPV) vaccine;
• who have any serious acute, chronic or progressive disease
• who have epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome;
• who have a known or suspected impairment/alteration of immune function, either congenital or acquired
• who are 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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MenACWY + Tdap + HPV; Subjects received MenACWY concomitantly with Tdap and HPV at study month 0 followed by two injections of HPV at month 2 and 6	Biological: Novartis Meningococcal ACWY Conjugate Vaccine; One dose of vaccine administered intramuscularly
Experimental: MenACWY →Tdap → HPV; Subjects received MenACWY at study month 0 followed by one injection of Tdap at month 1, followed by three injections of HPV at months 2, 4, and 8	Biological: Novartis Meningococcal ACWY Conjugate Vaccine; One dose of vaccine administered intramuscularly
Experimental: Tdap →MenACWY → HPV; Subjects received Tdap at month 0 followed by one injection of MenACWY at month 1, followed by three injections of HPV at months 2, 4, and 8	Biological: Tdap Vaccine; One dose of vaccine administered intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Seroresponse	Immune responses to MenACWY, as measured by the percentage of hSBA seroresponders, when given: (a) alone; (b) concomitantly with a Tetanus diphtheria acellular pertussis (Tdap) vaccine and a Human Papillomavirus Recombinant (HPV) vaccine; and (c) when given one month after a Tdap vaccine. Seroresponse to MenACWY: For a subject with baseline hSBA titer <1:4, seroresponse is defined as a postvaccination hSBA titer ≥ 1:8; for a subject with baseline hSBA titer ≥ 1:4, seroresponse is defined as a postvaccination hSBA titer of at least 4 times the baseline.	1 month post MenACWY vaccination
Percentage of Subjects With Antidiphtheria and Antitetanus Toxin ≥1.0 IU/mL	To compare the immune response to Tdap given concomitantly with MenACWY and HPV vaccine with the immune response to Tdap when administered alone	1 month post Tdap vaccination
Geometric Mean Concentrations (GMC) of Antipertussis Toxin (Anti-PT), Antifilamentous Hemagglutinin (Anti-FHA), and Antipertactin (Anti-PRN)	To compare the immune response of Tdap given concomitantly with MenACWY and HPV vaccine with the immune response of Tdap when administered alone	1 month post Tdap vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Concomitant and Sequential Vaccination on hSBA Geometric Mean Titers (GMTs) for A, C, W, and Y Serogroups	The immune responses to the MenACWY conjugate vaccine, as measured by the hSBA Geometric Mean Titers (GMTs) when given: (a) alone, (b) concomitantly with the Tdap vaccine and the HPV vaccine, and (c) when given one month after the Tdap vaccine.	1 month post MenACWY vaccination
Percentage of Subjects With Anti-HPV Seroconversion	To compare the immune response of HPV vaccine given concomitantly with MenACWY and Tdap to the response when HPV vaccine is given alone. (Immune response against HPV virus-like particles (VLPs) for types 6, 11, 16, and 18 was measured at one month after the third HPV vaccination.) Anti-HPV Seroconversion (SC): SC was defined as negative (baseline HPV titer < type-specific cut-off) for anti-HPV and anti-HPV ≥ an HPV type-specific cut-off at one month after the third HPV injection.	1 month post third HPV vaccination
Geometric Mean Titers (GMTs) of Anti-HPV by Competitive Luminex Immunoassay	To compare the immune response of HPV vaccine given concomitantly with MenACWY and Tdap to the response when HPV vaccine is given alone. (Immune response against HPV virus-like particles (VLPs) for types 6, 11, 16, and 18 was measured at one month after the third HPV vaccine vaccination.)	1 month post third HPV vaccination
Percentage of Subjects With hSBA ≥ 1:8, hSBA Titer ≥ 1:4, for A, C, W, and Y Serogroups	The immune responses to MenACWY, as measured by the percentage of subjects with hSBA titer ≥ 1:8, hSBA titer ≥ 1:4, when given: (a) alone, (b) concomitantly with Tdap and HPV vaccine; and (c) when given one month after Tdap.	1 month post MenACWY vaccination
The Effect of Sequential Vaccination on Immunogenicity for Diphtheria and Tetanus	The immune response to the Tdap vaccine, as measured by the percentage of subjects with antidiphtheria and antitetanus toxin ≥1.0 IU/mL.	1 month post Tdap vaccination
Geometric Mean Concentrations (GMC) for Diphtheria and Tetanus	To compare the immune response of Tdap, as measured by the antidiphtheria and antitetanus GMCs, when administered one month after the MenACWY vaccine with the immune response of the Tdap vaccine when administered alone.	1 month post Tdap vaccination
Geometric Mean Titers (GMT) of Pertussis Antigens	To compare the immune response to Tdap administered one month after MenACWY with the immune response to Tdap administered alone.	1 month post Tdap vaccination
Percentages of Subjects With at Least a 4-fold Rise for PT, FHA, and PRN	To compare the immune response of Tdap, defined by the percentage of subjects with a 4-fold rise in antibody titer over baseline against PT, FHA, PRN, when administered one month after the MenACWY with the immune response of Tdap when administered alone.	1 month post Tdap vaccination
Number of Subjects With at Least One Reactogenicity Sign After MenACWY and Tdap Vaccination.	Number of subjects with specified local and systemic reactions were assessed when MenACWY was given alone, one month after Tdap, and concomitantly with Tdap and HPV vaccine.	Days 1 to 7
Number of Subjects With at Least One Reactogenicity Sign After Each HPV Vaccination	Number of subjects with specified local and systemic reactions were solicited for 7 days after the HPV vaccination.	Days 1 to 7

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Arguedas A, Soley C, Loaiza C, Rincon G, Guevara S, Perez A, Porras W, Alvarado O, Aguilar L, Abdelnour A, Grunwald U, Bedell L, Anemona A, Dull PM. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines. Vaccine. 2010 Apr 19;28(18):3171-9. doi: 10.1016/j.vaccine.2010.02.045. Epub 2010 Feb 26.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 17, 2007
• First Submitted That Met QC Criteria: August 17, 2007
• First Posted (Estimate): August 20, 2007

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: vaccine; adolescents; meningitis; Meningococcal
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Central Nervous System Infections; DNA Virus Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Tumor Virus Infections; Clostridium Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Whooping Cough; Tetanus; Meningitis, Meningococcal; Meningitis; Papillomavirus Infections; Physiological Effects of Drugs; Immunologic Factors; Gastrointestinal Agents; Cathartics; Vaccines; Lactitol
• Other Study ID Numbers: V59P18