Study of DTap-IPV Compared to DAPTACEL® and IPOL® as the 5th Dose in Children 4 to 6 Years of Age

Tetanus Clinical Trial

Official title:

Safety and Immunogenicity of DTap-IPV (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined With Inactivated Poliovirus Vaccine) Compared to DAPTACEL® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) + IPOL® (Poliovirus Vaccine Inactivated) as the 5th Dose in Children 4 to 6 Years of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01346293
• Other study ID #: M5I02
• Secondary ID: U1111-1116-4842
• Status: Completed
• Phase: Phase 3
• First received: April 29, 2011
• Last updated: May 28, 2015
• Start date: April 2011
• Est. completion date: September 2013

Study information

• Verified date: May 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 study was designed to compare the safety and immunogenicity of DTap-IPV with DAPTACEL® + IPOL® as the 5th dose booster in children ≥ 4 to < 7 years of age in the US and Puerto Rico who were previously vaccinated with DAPTACEL® and/or Pentacel® vaccines only.

Primary Objectives:

• To compare the pertussis [Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN), and Fimbriae Types 2 and 3 (FIM)] booster responses and geometric mean concentrations (GMCs) (as measured by enzyme-linked immunosorbent assay [ELISA]) following DTap-IPV vaccination to those elicited following DAPTACEL® + IPOL® vaccination when administered as a 5th dose.

• To compare the diphtheria and tetanus booster responses and GMCs (as measured by ELISA) following DTap-IPV vaccination with those elicited following DAPTACEL® + IPOL® vaccinations when administered as a 5th dose .

• To compare the Inactivated Poliovirus Vaccine booster responses (as measured by neutralizing assay) following DTap-IPV vaccination with those elicited following DAPTACEL® + IPOL® vaccinations.

Observational Objectives:

• To compare the polio (types 1, 2, and 3) geometric mean titers (GMTs) following DTap-IPV vaccination with those elicited following DAPTACEL® + IPOL® vaccinations.

• To assess the safety of DTap-IPV vaccine or DAPTACEL® + IPOL® vaccine when administered as the fifth dose booster vaccine in participants previously vaccinated with DAPTACEL and/or Pentacel vaccines.

Description:

All participants will be randomized to receive either one dose each of DTap-IPV + Measles, Mumps, and Rubella Virus Vaccine Live (M-M-R®II) + VARIVAX® or one dose each of DAPTACEL® + IPOL® + M-M-R®II + VARIVAX® on Day 0.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3372
• Est. completion date: September 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 4 Years to 6 Years

Eligibility

Inclusion Criteria:

• Aged = 4 to < 7 years on the day of inclusion

• Informed consent form has been signed and dated by the parent/guardian before the first study-related procedure

• Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures

• Subject has documented completion of primary infant series and booster with DAPTACEL® and/or Pentacel® vaccine(s) only.

Exclusion Criteria:

• Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial vaccination

• Planned participation in another clinical trial during the present trial period

• Receipt of any vaccine in the 4 weeks preceding the trial vaccination, except for any influenza vaccine, which may be received at least 2 weeks before study vaccines

• Planned receipt of any vaccine in the 4 weeks following the trial vaccination except for any influenza vaccine, which may be received at least 2 weeks after study vaccines

• Receipt of 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)

• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

• History of diphtheria, tetanus, or pertussis infection, confirmed either clinically, serologically, or microbiologically

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

• Laboratory-confirmed thrombocytopenia, contraindicating intramuscular vaccination

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

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

• Identified as employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the investigator.

Study Design

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

Related Conditions & MeSH terms

• Diphtheria
• Measles
• Pertussis
• Polio
• Tetanus
• Whooping Cough

Intervention

Biological:
• Diphtheria and Tetanus Toxoids and Acellular Pertussis + Measles, Mumps, Rubella + Varicella Virus
0.5 mL, Intramuscular (DTap-IPV); Subcutaneous (M-M-R®II and VARIVAX®)
• Diphtheria and Tetanus Toxoids and Acellular Pertussis + Poliovirus + MMR + Varicella Virus
0.5 mL, Intramuscular (IM) DAPTACEL®; Subcutaneous (SC) MMR®II and VARIVAX®; IM or SC IPOL®
• Diphtheria and Tetanus Toxoids and Acellular Pertussis + Measles, Mumps, Rubella + Varicella Virus
0.5 mL, Intramuscular (DTap-IPV); Subcutaneous (M-M-R®II and VARIVAX®)
• Diphtheria and Tetanus Toxoids and Acellular Pertussis + Poliovirus + MMR + Varicella Virus
0.5 mL, Intramuscular (IM) DAPTACEL®; Subcutaneous (SC) MMR®II and VARIVAX®; IM or SC IPOL®

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	Number of Participants With Seroprotection Against the Tetanus and Diphtheria Antigens Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Anti-Tetanus antibodies were measured by ELISA. Anti diphtheria antibodies were measured by a toxin neutralization test. Seroprotection for anti-tetanus and anti-diphtheria was defined as antibody concentrations =0.1 IU/ml and =1.0 IU/ml.	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Other	Number of Participants With Seroprotection Against the Polio Antigens Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Anti-Poliovirus types 1, 2, and 3 titers were measured by neutralization assay. Seroprotection for anti-polio types was defined as antibody titers =1:8 dilution.	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Other	Number of Participants With Booster Response to the Polio Antigens Following Vaccination With Inactivated Poliovirus (IPV) Vaccine as a 4th or 5th Dose	Anti-Poliovirus types 1, 2, and 3 titers were measured by neutralization assay. Four-fold rise in booster responses between groups was defined as post/pre-vaccination =4.	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Other	Summary of Anti-Polio Geometric Mean Titers in Participants That Received Inactivated Poliovirus (IPV) Vaccine as a 4th and 5th Dose	Anti-Poliovirus types 1, 2, and 3 titers were measured by neutralization assay.	Day 0 (pre-booster vaccination) and Day 28 post-booster vaccination	No
Other	Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Solicited injection-site: Pain, Erythema, Swelling, Extensive Swelling of Vaccinated Limb, Change in Limb Circumference. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 injection-site: Pain, Incapacitating, unable to perform usual activities; Erythema, Swelling, =50 mm; Change in limb circumference >50 mm increase over pre-vaccination measurement; Extensive limb swelling (ELS) was considered severe. Grade 3 systemic reactions: Fever =39.0°C; Headache, Malaise, and Myalgia Significant, prevents daily activity.	Day 0 up to Day 28 post-final vaccination	No
Primary	Number of Participants With Booster Response to the Pertussis Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Booster responses to pertussis antigens [pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM)] were measured by enzyme-linked immunosorbent assay (ELISA). Booster responses were defined as participants with either a pre-vaccination antibody concentration less than lower limit of quantitation (	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Primary	Geometric Mean Concentrations of the Pertussis Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Geometric mean concentrations to pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae types 2 and 3 [FIM]) were measured by enzyme-linked immunosorbent assay (ELISA).	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Primary	Number of Participants With Booster Response to Tetanus and Diphtheria Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Anti-Diphtheria antibodies were measured by a toxin neutralization test. Booster responses were defined as participants with a pre-vaccination antibody concentration <0.1 IU/ml, achieving a post-vaccination level =0.4 IU/ml, or a pre-vaccination antibody concentration =0.1 IU/ml but <2.0 IU/ml, achieving a 4-fold rise rate post-vaccination, or a pre-vaccination antibody concentration =2.0 IU/ml, achieving a 2-fold response.	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Primary	Geometric Mean Concentrations of the Tetanus and Diphtheria Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Geometric mean concentrations to anti-tetanus and anti-diphtheria were measured by enzyme-linked immunosorbent assay (ELISA).	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Primary	Number of Participants With Booster Response to Polio Antigens Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Anti-poliovirus types 1, 2, and 3 titers were measured by neutralization assay. Booster responses were defined as participants with a pre-vaccination antibody concentration <1:8 dil, achieving a post-vaccination level =1:8 dil, or a pre-vaccination antibody concentration =1:8 dil, achieving a 4-fold response.	Day 0 (pre-vaccination) and Day 28 post-vaccination	No
Primary	Geometric Mean Concentrations of Polio Antibodies Before and Following Vaccination With Either DTaP-IPV or DAPTACEL® + IPOL® Vaccine	Geometric mean concentrations to anti-polio were measured by enzyme-linked immunosorbent assay (ELISA).	Day 0 (pre-vaccination) and Day 28 post-vaccination	No

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