DTaP-IPV/Hib Vaccine Primary & Booster Vaccinations Versus Co-administration of DTaP-IPV and Hib Vaccine in Japanese Infants

Immunogenicity and Safety of the DTaP-IPV/Hib Vaccine SP0204) Given as Three-dose Primary and One-dose Booster Vaccinations Versus Co-administration of DTaP-IPV Vaccine (DD-687) and Hib Vaccine (DF-098) in Infants in Japan

Primary objective:

• To demonstrate the non-inferiority in terms of seroprotection rates (Hib antigen (PRP), Diphtheria, Tetanus, and Pertussis antigens (PT and FHA), and polio types 1, 2 and 3 antigens) of investigational arm (Group A: DTaP-IPV/Hib) versus control arm (Group B: DTaP-IPV and Hib vaccines administered at separate sites), one month after the primary vaccination (all antigens).

Secondary objectives:

• To describe immune responses against all vaccine antigens with no pre-specified hypothesis, and at all time points (pre-dose 1, post-dose 3, pre-dose 4 and post-dose 4) in the two study groups (Group A and Group B).
• To describe the safety after each dose of each vaccine in the two study groups (Group A and Group B).
• To describe immune responses against all vaccine antigens with no pre-specified hypothesis, and at all time points (pre-dose 1, post-dose 3, pre-dose 4 and post-dose 4 (Group C)

Study Overview

• Status: Completed
• Conditions: Pertussis; Tetanus; Diphtheria; Bacterial Meningitis; Poliomyelitis
• Intervention / Treatment: Biological: DTaP-IPV/Hib Combined vaccine; Biological: DTaP-IPV/Hib Combined vaccine; Biological: DTaP-IPV vaccine and Hib vaccine

Detailed Description

Participants will be enrolled in two steps (Cohort 1 and Cohort 2). Step one will enroll Cohort 1 made of 40 participants randomized in two groups with a 1:1 ratio.

After review of the local and systemic adverse events occurring during the 7 Days following the first dose administered in these subjects, 2nd vaccination of Cohort 1 participants will resume and enrollment of the participants of Cohort number 2 will start. Step two will enroll Cohort 2 made of subjects randomized in two groups with a 1:1 ratio.

A sub-study Group C will be enrolled and will receive the vaccine by intramuscular route.

• Study Type: Interventional
• Enrollment (Actual): 424
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
  • Chiba, Japan
  • Fukui, Japan
  • Fukuoka, Japan
  • Gunma, Japan
  • Hokkaido, Japan
  • Miyagi, Japan
  • Nagano, Japan
  • Osaka, Japan
  • Shizuoka, Japan
  • Tokyo, Japan
  • Yamanashi, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 2 months to 68 months inclusive (recommended 3 to 8 months for Groups A and B; 2 months for Group C) on the day of inclusion
• Informed consent form signed by the parent(s) or other legal representative
• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Fever ≥ 37.5°C (axillary temperature) on the day of inclusion
• Any serious disease whether acute or chronic
• Past or current medical history of Guillain-Barre syndrome, acute thrombocytopenic purpura or encephalopathy
• History of diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b infections
• History of a life threatening reaction to a vaccine containing the same substances of the study vaccine
• History of anaphylaxis to any of the study vaccine components
• Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis or Haemophilus influenzae type b infections with a trial vaccine or another vaccine
• Congenital or current acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroids therapy
• Participation in another clinical trial preceding the trial inclusion
• Planned participation in another clinical trial during the present trial period
• Blood or blood-derived products received in the past or current or planned administration during the trial (including immunoglobulins)
• Any vaccination with live vaccines within the past 27 days preceding the first trial vaccination
• Any vaccination with inactivated vaccines within the past 6 days preceding the first trial vaccination
• Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or HIV infection
• Subject ineligible according to the Investigator's clinical judgment
• Identified as employee 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 member (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: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (SP0204); Participants will receive DTaP-IPV/Hib vaccine administered subcutaneously	Biological: DTaP-IPV/Hib Combined vaccine; 0.5 mL, Subcutaneously. 3 times, each given 3 to 8 weeks apart; Other Names: SP0204; Biological: DTaP-IPV/Hib Combined vaccine; 0.5 mL, Intramuscularly. 3 times, each given 4 to 8 weeks apart; Other Names: SP0204
Active Comparator: Group B (control); Participants will be given a co-administration of DTaP-IPV vaccine and Hib vaccine subcutaneously	Biological: DTaP-IPV vaccine and Hib vaccine; 0.5 mL each, Subcutaneously, 3 times, each given 3 to 8 weeks apart; Other Names: DD 687; DF 098
Experimental: Group C; Participants will receive DTaP-IPV/Hib vaccine administered intramuscularly	Biological: DTaP-IPV/Hib Combined vaccine; 0.5 mL, Subcutaneously. 3 times, each given 3 to 8 weeks apart; Other Names: SP0204; Biological: DTaP-IPV/Hib Combined vaccine; 0.5 mL, Intramuscularly. 3 times, each given 4 to 8 weeks apart; Other Names: SP0204

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with anti-Diphtheria level ≥ 0.1 IU/mL post-dose 3	Anti-Diphtheria antibody titers will be assayed by neutralization test on Vero cells culture in comparison to the WHO equine antitoxin standard (seroneutralization)	21 Days post-dose 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with Seroprotection to vaccine antigens following vaccination	Seroprotection is defined as: percentage of participants with anti-Diphtheria and anti Tetanus antibody levels ≥0.01, ≥0.1 and ≥1.0 IU/mL	Day 0 (pre-vaccination ) and 21 Days post-dose 3
Geometric Mean Titer (GMT) of antibodies to vaccine antigens following vaccination	Anti-Diphtheria antibody titers will be assayed by neutralization test on Vero cells culture in comparison to the WHO equine antitoxin standard (seroneutralization)	21 Days post-dose 3
Information concerning the safety in terms of solicited injection site and systemic reactions, unsolicited adverse events, and serious adverse events post vaccination with DTaP IPV/Hib vaccine.	Solicited injection site reactions: Tenderness, Erythema, Swelling and Induration; Solicited Systemic Reactions: Fever (Temperature), Vomiting, Crying abnormal, Drowsiness, Appetite lost and Irritability.	Day 0 (post-vaccination) up to 21 days post each vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Medical Director, Sanofi K.K.

Publications and helpful links

General Publications

• Nakayama T, Vidor E, Tsuzuki D, Nishina S, Sasaki T, Ishii Y, Mizukami H, Tsuge H. Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan. J Infect Chemother. 2020 Jul;26(7):651-659. doi: 10.1016/j.jiac.2019.11.012. Epub 2020 Apr 16.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): May 28, 2016
• Study Completion (Actual): May 28, 2016

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 22, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Pertussis; Diphtheria; Tetanus; Poliomyelitis; Bacterial meningitis; DTaP-IPV/Hib Combination vaccine
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neuromuscular Diseases; Central Nervous System Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Clostridium Infections; Corynebacterium Infections; Central Nervous System Bacterial Infections; Myelitis; Whooping Cough; Tetanus; Diphtheria; Meningitis; Poliomyelitis; Meningitis, Bacterial; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: J2I02 (EFC13640); U1111-1143-9112 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org