Study of Menactra® in Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age

Tetanus Clinical Trial

Official title:

An Immunogenicity and Safety Evaluation of Menactra® (Meningococcal [Groups A, C, Y and W-135] Polysaccharide Diphtheria Toxoid Conjugate Vaccine) When Administered to Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01659996
• Other study ID #: MTA55
• Secondary ID: U1111-1120-1368
• Status: Completed
• Phase: Phase 4
• First received: August 2, 2012
• Last updated: November 10, 2015
• Start date: July 2012
• Est. completion date: September 2015

Study information

• Verified date: November 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to further characterize the safety and immunogenicity of Menactra® in the population <2 years of age when administered alone and when the second dose is administered concomitantly with the 4th dose of Pentacel®, a licensed pediatric vaccine.

Primary Objectives:

• To evaluate and compare the antibody responses to meningococcal serogroups A, C, Y, and W-135 induced by 2 injections of Menactra® in subjects aged 9 months at the first vaccination visit and 15 to 18 months at the second vaccination visit.

• To evaluate and compare the antibody responses to Pertussis (pertussis toxoid [PT], filamentous haemagglutinin [FHA] and pertactin [PRN]) antigens induced by a dose of Pentacel® when administered concomitantly with Menactra® to those elicited by a dose of Pentacel® administered alone.

• To evaluate and compare the antibody responses to polyribosylribitol phosphate (PRP), tetanus and diphtheria antigens induced by a dose of Pentacel® when administered concomitantly with Menactra® to those elicited by a dose of Pentacel® alone.

Observational Objectives:

• To describe the safety profile (immediate unsolicited AEs within 30 minutes of each trial vaccination, solicited reactions within 7 days of each vaccination, unsolicited AEs within 30 days of each vaccination, and serious adverse events [SAEs] throughout the course of the trial from Day 0 up to Day 30 after the last trial vaccination[s]) in all trial groups

• To describe the antibody responses to meningococcal serogroups A, C, Y, and W-135, measured by SBA HC, 30 days after the second Menactra® administration

• To describe the antibody responses to Pentacel® (PT, FHA, PRN, FIM, diphtheria, tetanus, polio, PRP) measured by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or functional assays.

Description:

Participants will be vaccinated according to their randomized groups at age 9 months and at age 15 to 18 months. They will undergo immunogenicity assessment and safety monitoring post-vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1394
• Est. completion date: September 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 9 Months to 18 Months

Eligibility

Inclusion Criteria:

• Aged 9 months (249 to 305 days) for Groups 1 and 2, or 15 to 18 months (420 to 570 days) for Group 3 on the day of the first trial visit

• Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative

• Received 3 doses of any DTaP-containing vaccines

• Received 3 doses of a Hib-containing vaccine, or 2 doses if the subject received PRP-OMP (PedvaxHIB® or Comvax®[HepB-Hib])

• Received at least 3 doses of a CRM197-based pneumococcal conjugate vaccine (Pneumococcal conjugate vaccine [PCV] or 13-Valent pneumococcal conjugate vaccine [PCV13])

• Subject and parent/ legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Participation in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure

• Receipt of any vaccine in the 4 weeks preceding each trial vaccination or planned receipt of any vaccine in the 4 weeks following each trial vaccination, except for influenza vaccination, which may be received at least 2 weeks before or after the trial vaccination(s)

• Vaccination against meningococcal disease with either the trial vaccine or another vaccine, or receipt of the 4th dose of any DTaP-containing vaccines, receipt of the 4th dose of a Hib-containing vaccine, or receipt of the 3rd dose of PRP-OMP (PedvaxHIB® or Comvax® [Hep B-Hib]) prior to enrollment or during the conduction of the trial, except for Group 1 subjects, who may receive Hib vaccine at 12 months

• Receipt of immune globulins, blood or blood-derived products in the past 3 months

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Topical steroids are not included in this exclusion criterion

• History of invasive meningococcal infection, confirmed either clinically, serologically, or microbiologically

• Personal history of Guillain-Barré Syndrome

• History of encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis containing vaccine that is not attributable to another identifiable cause

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to one of the vaccines used in the trial or to a vaccine containing any of the same substances

• Known thrombocytopenia, as reported by the parent/ legally acceptable representative, contraindicating intramuscular vaccination

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination

• In an emergency setting or hospitalized involuntarily

• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion

• Moderate or severe acute illness/ infection (according to investigator judgment) or febrile illness (temperature = 100.4°F [= 38.0°C]) on the day of vaccination. A prospective subject should not be included in the trial until the condition has resolved or the febrile event has subsided

• Receipt of oral or injectable antibiotic therapy within 72 hours prior to any trial blood draw (topical antibiotics, drops, or ointments are not included in this criterion)

• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diphtheria
• Haemophilus Influenzae Serotype b (Hib)
• Meningitis
• Meningococcal Infection
• Meningococcal Infections
• Pertussis
• Tetanus

Intervention

Biological:
• Meningococcal polysaccharide diphtheria toxoid conjugate
0.5 mL, Intramuscular
• Meningococcal polysaccharide diphtheria toxoid conjugate + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed
0.5 mL, Intramuscular
• Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate
0.5 mL, Intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Geometric Mean Titers of Individual Meningococcal Antibodies in Serum Bactericidal Assay With Human Complement (SBA-HC) Analysis Following Vaccination With Menactra Vaccine	Geometric mean titers (GMTs) of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay with human complement (SBA HC) before any vaccination and post-vaccination 2	Day 0 (pre-vaccination) and Day 30 post-vaccination 2	No
Other	Geometric Mean Titers of Individual Antibodies to Filamentous Hemagglutinin, Pertactin, Diphtheria, Tetanus and Polio Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Filamentous hemagglutinin (FHA), Fimbriae types 2 and 3 (FIM), Pertactin (PRN) and anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA); anti-Diphtheria antibodies were measured by a toxin neutralization test.	Day 0 (pre-vaccination) and Day 30 post-vaccination 2	No
Other	Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Solicited injection-site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - = 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - = 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses = 3 feeds / meals or refuses most feeds / meals; and Irritability - Inconsolable.	Day 0 to Day 7 after any vaccination	No
Other	Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination at 9 Months of Age With Menactra Vaccine.	Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - = 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - = 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses = 3 feeds / meals or refuses most feeds/meals; and Irritability - Inconsolable.	Day 0 to Day 7 after 9-month vaccination	No
Other	Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only, or Menactra Concomitantly With Pentacel Vaccine	Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - = 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - = 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses = 3 feeds/meals or refuses most feeds/meals; and Irritability - Inconsolable.	Day 0 to Day 7 after the 15 to 18 month vaccination	No
Primary	Percentage of Study Participants Achieving Menactra Response for Meningococcal Serogroups A, C, Y, and W-135 Following the Second Menactra Vaccination	Titers of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay using human complement (hSBA or SBA-HC).; Menactra vaccine response defined as subjects with an hSBA titer <1:8 at baseline achieving an hSBA titer =1:8, and subjects with an hSBA titer =1:8 at baseline achieving a = 4-fold increase in hSBA titer.	Day 30 post second Menactra vaccination	No
Primary	Geometric Mean Concentrations of Pertussis Vaccine Antibodies Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).	Day 30 post-vaccination 2	No
Primary	Percentage of Participants With Pertussis Vaccine Responses Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), and Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Pertussis response was defined as: =4 × baseline concentration, if the anti-pertussis antibody concentration at baseline is <4 × lower limit of quantification (LLOQ), Or =2 × baseline concentration, if the anti-pertussis antibody concentration at baseline is =4 × LLOQ	Day 30 post-vaccination 2	No
Primary	Percentage of Participants With Antibody Responses to Diphtheria, Tetanus and Polyribosylribitol Phosphate Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine	Anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA), anti-polyribosylribitol phosphate (PRP) antibodies were measured using a Farr-type radioimmunoassay, and anti-diphtheria antibodies were measured by a toxin neutralization test.; The vaccine responses were defined as: Anti-PRP antibody concentrations =1.0 µg/mL; Anti-tetanus antibody concentrations =1.0 IU/mL and Anti-diphtheria antibody concentrations =1.0 IU/mL, respectively, 30 days after vaccination with Pentacel® in participants in Groups 2 and 3.	Day 30 post-vaccination 2	No

External Links

•   Link
•   Link