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

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

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.

Study Overview

• Status: Completed
• Conditions: Measles; Pertussis; Tetanus; Diphtheria; Polio
• Intervention / Treatment: Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Measles, Mumps, Rubella + Varicella Virus; Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis + Poliovirus + MMR + Varicella Virus

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 3372
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
    • Birmingham, Alabama, United States, 35205
    • Birmingham, Alabama, United States, 35244
    • Pinson, Alabama, United States, 35126
    • Trussville, Alabama, United States, 35173
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Scottsdale, Arizona, United States, 85258
    • Scottsdale, Arizona, United States, 85255
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
    • Little Rock, Arkansas, United States, 72205
  • California
    • La Puente, California, United States, 91744
    • Paramount, California, United States, 90723
    • Roseville, California, United States, 95661
    • Santa Clara, California, United States, 95051
    • West Covina, California, United States, 91790
  • Colorado
    • Longmont, Colorado, United States, 80501
    • Thornton, Colorado, United States, 80233
  • Florida
    • St. Petersburg, Florida, United States, 33713
  • Georgia
    • Marietta, Georgia, United States, 30062
    • Woodstock, Georgia, United States, 30189
  • Indiana
    • Indianapolis, Indiana, United States, 46256
    • New Albany, Indiana, United States, 47150
  • Kansas
    • Overland Park, Kansas, United States, 66213
    • Topeka, Kansas, United States, 66604
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
    • Louisville, Kentucky, United States, 40202
    • Louisville, Kentucky, United States, 40207
    • Nicholasville, Kentucky, United States, 40356
    • Owensboro, Kentucky, United States, 42303
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
    • Haughton, Louisiana, United States, 71037
  • Maryland
    • Annapolis, Maryland, United States, 21401
  • Massachusetts
    • Frederick, Massachusetts, United States, 21702
    • Woburn, Massachusetts, United States, 01801
  • Missouri
    • Bridgeton, Missouri, United States, 63044
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
    • Boys Town, Nebraska, United States, 68010
    • Lincoln, Nebraska, United States, 68504
    • Lincoln, Nebraska, United States, 68516
    • Omaha, Nebraska, United States, 68198
  • New York
    • Brooklyn, New York, United States, 11201
  • North Dakota
    • Fargo, North Dakota, United States, 58104
  • Ohio
    • Cincinnati, Ohio, United States, 45245
    • Fairfield, Ohio, United States, 45014
    • Youngstown, Ohio, United States, 44505
  • Oklahoma
    • Midwest City, Oklahoma, United States, 73110
  • Oregon
    • Gresham, Oregon, United States, 97030
  • Pennsylvania
    • Collegeville, Pennsylvania, United States, 19426
    • Pittsburgh, Pennsylvania, United States, 15241
    • Scranton, Pennsylvania, United States, 18510
  • Tennessee
    • Bristol, Tennessee, United States, 37620
  • Texas
    • Austin, Texas, United States, 78745
    • Dallas, Texas, United States, 75230
    • Houston, Texas, United States, 77025
    • San Antonio, Texas, United States, 78229
  • Utah
    • Clinton, Utah, United States, 84015
    • Layton, Utah, United States, 84041
    • Murray, Utah, United States, 84107
    • Orem, Utah, United States, 84057
    • Roy, Utah, United States, 84067
    • Springville, Utah, United States, 84663
    • Syracuse, Utah, United States, 84075
  • Virginia
    • Burke, Virginia, United States, 22015
    • Charlottesville, Virginia, United States, 22903
    • Charlottesville, Virginia, United States, 22902
    • Charlottesville, Virginia, United States, 22911
    • Midlothian, Virginia, United States, 23113
    • Vienna, Virginia, United States, 22180
  • Washington
    • Spokane, Washington, United States, 99202
    • Spokane, Washington, United States, 99218
  • West Virginia
    • Huntington, West Virginia, United States, 25701

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group 1; Participants will receive concomitantly a dose of DTap-IPV, a dose of M-M-R®II, and a dose of VARIVAX® vaccine on Day 0	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®); Other Names: VARIVAX®; DTap-IPV; M-M-R®II
Experimental: Study Group 2; Participants will receive concomitantly a dose of DAPTACEL®, a dose of IPOL®, a dose of M-M-R®II, and a dose of VARIVAX® vaccines on Day 0	Biological: 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®; Other Names: VARIVAX®; M-M-R®II; DAPTACEL®; IPOL®
Experimental: Study Group 3; Participants will receive concomitantly a dose of DTap-IPV with or without a dose of M-M-R®II and a dose of VARIVAX® on Day 0	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®); Other Names: VARIVAX®; DTap-IPV; M-M-R®II
Experimental: Study Group 4; Participants will receive concomitantly a dose of DAPTACEL® vaccine, a dose of IPOL® vaccine with or without a dose of M-M-R®II and a dose of VARIVAX® vaccines on Day 0	Biological: 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®; Other Names: VARIVAX®; M-M-R®II; DAPTACEL®; IPOL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 (<LLOQ), achieving a post-vaccination level ≥4X LLOQ, or pre-vaccination antibody concentrations ≥LLOQ but <4X LLOQ, achieving a 4-fold rise rate of post-vaccination, or a pre-vaccination antibody concentration ≥4X LLOQ, achieving a 2-fold response.	Day 0 (pre-vaccination) and Day 28 post-vaccination
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Smith MJ, Jordanov E, Sheng X, Tsang PH. Safety and Immunogenicity of DTaP5-IPV Compared With DTaP5 Plus IPV as the Fifth Dose in Children 4-6 Years of Age. Pediatr Infect Dis J. 2017 Mar;36(3):319-325. doi: 10.1097/INF.0000000000001427.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: April 29, 2011
• First Posted (Estimate): May 2, 2011

Study Record Updates

• Last Update Posted (Estimate): June 3, 2015
• Last Update Submitted That Met QC Criteria: May 28, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Pertussis; Diphtheria; Tetanus; DTap-IPV; DAPTACEL®; VARIVAX®
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neurologic Manifestations; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Neuromuscular Manifestations; Actinomycetales Infections; Clostridium Infections; Hypocalcemia; Calcium Metabolism Disorders; Corynebacterium Infections; Whooping Cough; Tetanus; Diphtheria; Tetany
• Other Study ID Numbers: M5I02; U1111-1116-4842 (Other Identifier: WHO)