Study of the DTaP-IPV-Hep B-PRP~T Combined Vaccine Following a Primary Series of DTacP IPV-HepB-PRP-T or Infanrix Hexa™

Phase 3

Completed

• Conditions: Hepatitis B; Diphtheria; Pertussis; Tetanus; Poliomyelitis; Haemophilus Influenzae Type B Infection
• Interventions: Biological: DTaP-IPV-Hep B-PRP~T vaccine (Batch 2); Biological: DTaP-IPV-Hep B-PRP~T vaccine (Batch 1); Biological: DTaP-IPV-Hep B-PRP~T vaccine (Batch 3); Biological: Infanrix Hexa™

• Registration Number: NCT00654901
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

This is a follow-up of Study A3L11 (NCT00404651).

Immunogenicity

* To describe the antibody persistence following a primary series vaccination of either DTaP-IPV-Hep B-PRP\~T or Infanrix hexa™.

* To describe the immunogenicity of a booster dose of DTaP-IPV-HepB-PRP\~T in a subset of subjects.

Safety

- To describe the safety profile after a booster dose of DTacP-IPV-HepB-PRP\~T.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2008-04-03
• Study First Submitted QC: 2008-04-03
• Study First Posted: 2008-04-09
• Primary Completion: 2009-05
• Study Completion: 2009-07
• Results First Submitted: 2013-05-06
• Results First Submitted QC: 2013-05-06
• Results First Posted: 2013-06-26
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-08
• Last Update Posted: 2016-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 881

Inclusion Criteria

• Toddlers previously included in Study A3L11 (NCT00404651) who completed the three-dose primary series vaccination of either DTaP-IPV-HepB-PRP-T or Infanrix hexa™ at 2, 4 and 6 months of age
• Toddlers of 15 to 18 months (456 to 578 days) of age, inclusive
• Informed Consent Form signed by at least one parent or legal representative and two mandatory witnesses
• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria

• Participation in another clinical trial in the 4 weeks preceding the booster vaccination.
• Planned participation in another clinical trial during the present trial period.
• Congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroid therapy.
• Systemic hypersensitivity to any of the vaccine components or history of a life threatening reaction to a vaccine containing the same substances.
• Chronic illness at a stage that could interfere with trial conduct or completion.
• Blood or blood-derived products received in the last 3 months.
• Any vaccination in the 4 weeks preceding the booster vaccination.
• Any vaccination planned until the next visit.
• History of documented pertussis, tetanus, diphtheria, polio, Haemophilus influenzae type b or hepatitis B (HB) infection(s) (confirmed either clinically, serologically or microbiologically).
• Administration of a vaccine against pertussis, tetanus, diphtheria, polio, Hib, and/or hepatitis B infection(s) since the end of participation in Study A3L11.
• Coagulopathy, thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination.
• Known maternal history of human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbsAg) or Hepatitis C seropositivity.
• Subjects with any related serious adverse event that occurred following the three-dose primary series administration of the investigational vaccine or of the reference vaccine in Study A3L11.
• History of seizures.
• Febrile (temperature ≥38.0°C) or acute illness on the day of inclusion
• Known contraindication to further vaccination with a pertussis vaccine, i.e.: Encephalopathy; Temperature >40.0°C within 48 hours following a vaccine injection, not due to another identifiable cause during the primary series; Inconsolable crying that occurred for >3 hours within 48 hours following vaccine injection during the primary series; Hypotonic hyporesponsive episode within 48 hours following vaccine injection during the primary series; Seizures with or without fever within 3 days following vaccine injection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DTaP-IPV-Hep B-PRP~T Batch 2	DTaP-IPV-Hep B-PRP~T vaccine (Batch 2)	Participants had received 3 primary doses of Batch 1 of Diphtheria (D), Tetanus (T), Pertussis (acellular, component \[aP\]), Hepatitis B (Hep B, \[recombinant DNA\]) and poliomyelitis (Inactivated \[IPV\]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP\~T) in Study A3L11 (NCT00404651) and will receive a booster dose of (DTaP-IPV-Hep B-PRP\~T) at Day 0 in the present study.
DTaP-IPV-Hep B-PRP~T Batch 1	DTaP-IPV-Hep B-PRP~T vaccine (Batch 1)	Participants had received 3 primary doses of Batch 1 of Diphtheria (D), Tetanus (T), Pertussis (acellular, component \[aP\]), Hepatitis B (Hep B, \[recombinant DNA\]) and poliomyelitis (Inactivated \[IPV\]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP\~T) in Study A3L11 (NCT00404651); and will receive a booster dose of (DTaP-IPV-Hep B-PRP\~T) at Day 0 in the present study.
DTaP-IPV-Hep B-PRP~T Batch 3	DTaP-IPV-Hep B-PRP~T vaccine (Batch 3)	Participants had received 3 primary doses of Batch 1 of Diphtheria (D), Tetanus (T), Pertussis (acellular, component \[aP\]), Hepatitis B (Hep B, \[recombinant DNA\]) and poliomyelitis (Inactivated \[IPV\]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP\~T) in Study A3L11 (NCT00404651) and will receive a booster dose of (DTaP-IPV-Hep B-PRP\~T) at Day 0 in the present study.
Infanrix Hexa™	Infanrix Hexa™	Participants had received 3 primary doses of Diphtheria (D), Tetanus (T), Pertussis (acellular, component \[aP\]), Hepatitis B (Hep B, \[recombinant DNA\]) and poliomyelitis (Inactivated \[IPV\]), (Infanrix Hexa™) plus Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed in Study A3L11 (NCT00404651) and received a booster dose of (DTaP-IPV-Hep B-PRP\~T) at Day 0 in the present study.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Antibody Persistence Before and Immunogenicity Response After Booster Vaccination With DTaP-IPV-Hep B-PRP~T Vaccine	Day 0 (pre-booster) and Day 30 (one month post-booster)	Antibody persistence and immunogenicity response: Level 1: ≥ 10 mIU/mL for hepatitis B (Hep B), ≥ 0.15 µg/mL for Haemophilus influenzae type b (PRP), and ≥ 0.01 IU/mL for diphtheria (D) and tetanus (T). Level 2: ≥ 100 mIU/mL (Hep B), ≥ 1.0 µg/mL (PRP), and ≥ 0.1 IU/mL (D and T) Level 3, ≥ 1.0 IU/mL (D and T). Anti-polio titers were defined as ≥ 8 (1.dil), and pertussis toxoid (PT) and filamentous hemagglutinin (FHA) by a 4 fold increase from Day 0.
Geometric Mean Titers of Antibodies Before and After Booster Vaccination With DTaP-IPV-Hep B-PRP~T	Day 0 (pre-booster) and Day 30 (one month post-booster)	Antibody titers were measured for hepatitis B (Hep B) by enhanced chemiluminescence detection, for Haemophilus influenzae type b (PRP) by Farr type radioimmunoassay, for diphtheria by toxin neutralization test, and for tetanus by enzyme linked immunosorbent assay (ELISA). Antibody titers were measured for poliovirus types 1, 2, and 3 by neutralization assay. Antibody titers were measured for pertussis toxoid (PT) and filamentous hemagglutinin (FHA) by ELISA.
Number of Participants With Solicited Injection Site or Systemic Reactions After Vaccination With DTaP-IPV-Hep B-PRP~T Vaccine	Days 0 up to 7 after any injection	Solicited Injection Site Reactions: Pain, Erythema, Swelling, Extensive Swelling of Vaccinated Limb. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability.; Grade 3 reactions were defined as: Pain, cries when injected limb is moved or movement of injected limb reduced; Erythema and swelling, ≥ 5cm; Extensive swelling of limb; Pyrexia, ≥ 39.6ºC; Vomiting ≥ 6 episodes/24 hours or requiring parenteral hydration; Somnolence, sleeping most of time or difficult to wake up; Anorexia, refuses ≥ feeds or most feeds; Irritability, inconsolable.