Study of the Booster Effect of DTaP-IPV-Hep B-PRP~T Combined Vaccine or Infanrix Hexa™ and Prevenar™ in Healthy Infants

Phase 3

Completed

• Conditions: Hepatitis B; Poliomyelitis; Diphtheria; Tetanus; Whooping Cough
• Interventions: Biological: DTaP-IPV-Hep B-PRP~T combined vaccine + Pneumococcal polysaccharide; Biological: DTaP-Hep B-IPV // Hib Vaccine + Pneumococcal polysaccharide; Biological: DTaP-IPV-Hep B-PRP~T + Pneumococcal polysaccharide vaccine

• Registration Number: NCT01444781
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

This is a follow-up of the primary series vaccination schedule in Study A3L24 (NCT01177722). The objectives are:

* To describe the antibody persistence to any antigen contained in the investigational DTaP-IPV-Hep B-PRP-T vaccine and Infanrix hexa™ prior to the booster dose

* To describe the safety and immunogenicity of the booster dose of either DTaP-IPV-Hep B-PRP-T or Infanrix hexa™ vaccine.

* To describe the immunogenicity of a booster dose of Prevenar™ given at 12 to 24 months.

Detailed Description

All participants who completed trial A3L24 (NCT01177722) will be recruited to participate in this trial. Those who received DTaP-IPV-Hep B-PRP-T combined vaccine will be randomized to receive either a booster dose of DTaP-IPV-Hep B-PRP-T or Infanrix hexa™ vaccine.

Those who received Infanrix hexa™ will receive a booster dose of DTaP-IPV-Hep B-PRP-T combined vaccine. All participants will receive a booster dose of Prevenar™ concomitantly.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2011-09-29
• Study First Submitted QC: 2011-09-30
• Study First Posted: 2011-10-03
• Primary Completion: 2013-04
• Study Completion: 2013-10
• Results First Submitted: 2014-06-12
• Status Verified: 2014-07
• Results First Submitted QC: 2014-07-14
• Last Update Submitted: 2014-07-14
• Results First Posted: 2014-07-16
• Last Update Posted: 2014-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1106

Inclusion Criteria

• Aged 12 to 24 months on the day of inclusion.
• Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness(es) if required by local regulations).
• Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures.
• Toddlers previously included in Study A3L24 who completed the three-dose primary series vaccination of either DTaP-IPV-Hep B-PRP~T or Infanrix hexa™ at 2,4 and 6 months of age according to protocol (both concomitantly administered with Prevenar™ and Rotarix™).

Exclusion Criteria

• Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the booster vaccinations.
• Planned participation in another clinical trial during the present trial period.
• Receipt of any vaccine in the 4 weeks preceding the booster vaccinations, except in case of pandemic influenza vaccination, which may be received at least two weeks before the study vaccines.
• Planned receipt of any vaccine in the 4 weeks following the trial vaccinations.
• Previous booster vaccination against pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b, hepatitis B and pneumococcal infection(s) with either the trial vaccine or another vaccine.
• Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response.
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 3 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• Laboratory-confirmed or clinical suspicion of personal or maternal seropositivity for Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C, as reported by the parent/guardian.
• History of pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b, hepatitis B and pneumococcal infection(s), confirmed either clinically, serologically, or microbiologically.
• At high risk for opportunistic infection during the trial.
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances.
• History of contraindication to receipt of pertussis-containing vaccine.
• Laboratory-confirmed or clinical suspicion of thrombocytopenia contraindicating Intramuscular vaccination.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
• History of seizures .
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
• Receipt of oral or injected antibiotic therapy within 72 hours prior to the first blood draw
• Febrile illness (temperature ≥ 38.0°C) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Group 1	DTaP-IPV-Hep B-PRP~T combined vaccine + Pneumococcal polysaccharide	Participants previously primed with DTaP-IPV-Hep B-PRP\~T, will receive one dose of DTaP-IPV-Hep B-PRP\~T vaccine + one dose of Prevenar™
Study Group 2	DTaP-Hep B-IPV // Hib Vaccine + Pneumococcal polysaccharide	Participants previously primed with DTaP-IPV-Hep B-PRP\~T, will receive one dose of Infanrix hexa™ vaccine + one dose of Prevenar™
Study Group 3	DTaP-IPV-Hep B-PRP~T + Pneumococcal polysaccharide vaccine	Participants previously primed with Infanrix hexa™ will receive one dose of DTaP-IPV-Hep B-PRP\~T + one dose of Prevenar™.

Primary Outcome Measures

Name	Time	Method
Summary of Diphtheria and Tetanus Post Primary Series Antibodies, Persistence and Booster Response Following Vaccination With Either DTaP-IPV Hep B-PRP T Vaccine or Infanrix Hexa Vaccine	Day 140 (Primary series) and Day 0 (Pre-booster)	Anti-Diphtheria (D) antibodies were measured by a toxin neutralization test. Anti-Tetanus (T) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Antibody persistence for anti-Diphtheria and anti-Tetanus antibodies was defined as titers ≥0.01 IU/mL and ≥0.1 IU/mL before the booster dose at Day 0. Booster response to Diphtheria and Tetanus was defined as antibody titers ≥0.01 IU/mL and ≥0.1 IU/mL at Day 30 post-booster vaccination.; Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers
Summary of Pertussis and Filamentous Haemagglutinin Post Primary Series Antibodies, Persistence and Booster Response Following Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine	Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination	Anti-Pertussis toxin (PT) and anti-Filamentous haemagglutinin (FHA) antibodies were measured by ELISA. Antibody persistence for anti-PT and anti-FHA was defined as titers ≥ lower limit of quantitation (LLOQ) before the booster dose at Day 0. Booster responses for PT and FHA at Day 30 were defined as: pre-vaccination antibody concentrations \< LLOQ and post-vaccination levels ≥ 4 x LLOQ, pre-vaccination antibody concentrations ≥ LLOQ but \< 4 x LLOQ and post/pre vaccination ≥ 4, and pre-vaccination antibody concentrations ≥ 4 x LLOQ and post/pre-vaccination ≥ 2.; Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers.
Summary of Polio Antibodies Post Primary Series, Persistence and Booster Response Following Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine	Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination	Anti-Poliovirus types 1, 2, and 3 antibodies were measured by neutralization assay. Antibody persistence for anti-Poliovirus 1, 2, and 3 was defined as antibody titers ≥8 (1/dil) before the booster dose at Day 0. Booster response to Poliovirus 1, 2, and 3 was defined as antibody titers ≥8 (1/dil) at Day 30.; Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers.
Summary of Hepatitis B and Haemophilus Influenzae Type B Post Primary Series Antibodies; Antibody Persistence, and Booster Response Following Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine	Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination	Anti-Hepatitis B antibodies were measured by the commercially available VITROS ECi/ECiQ Immunodiagnostic System. Anti-Haemophilus influenza type b capsular polyribosyl ribitol phosphate (PRP) antibodies were measured using a Farr type radioimmunoassay that used radiolabeled PRP (3H PRP) in the presence of 36Cl (volume marker). Anti-Hepatitis antibody titers ≥ 10 mIU/mL and ≥ 100 mIU/mL at Day 0 confirmed antibody persistence and booster response at Day 30. Anti-PRP antibody titers ≥ 0.15 µg/ml and ≥ 1.0 µg/ml at Day 0 confirmed antibody persistence and booster response at Day 30.; Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers.

Secondary Outcome Measures

Name	Time	Method
Summary of Immune Response Against Serotypes in the Prevenar Vaccine After Booster Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine	Day 30 after final booster vaccination	Anti-Streptococcus pneumococcal type specific antibody (anti-Pn PS) was measured by ELISA. Booster response to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F was defined as antibody titers ≥0.35 µg/mL at Day 30.
Summary of Geometric Mean Titers to Prevenar Vaccine Antibodies After Booster Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine	Day 30 after final booster vaccination	Anti-Streptococcus pneumococcal type specific antibody (anti-Pn PS) was measured by ELISA.
Summary of Booster Response to Vaccine Antigens Before and After Booster Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine By Age Strata	Day 0 (pre-vaccination) and Day 30 after final booster vaccination	Anti-PT and anti-FHA antibodies were measured by ELISA.
Summary of Geometric Mean Titers to Vaccine Antigens After Booster Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine by Age Strata	Day 30 after final booster vaccination	Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-FHA antibodies were measured by ELISA. Anti-Poliovirus types 1, 2, and 3 were measured by neutralization assay.
Number of Participants Reporting a Solicited Injection Site or Systemic Reactions Following Booster Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine	Day 0 up to Day 7 after final booster vaccination	Solicited injection site: Pain, Erythema, Swelling, and Extensive swelling of vaccinated limb; Solicited systemic reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, and Irritability. Grade 3 Injection site: Pain, Cries if limb is moved or reduced movement; Erythema and Swelling, ≥5 cm; Extensive swelling of limb, Severe. Grade 3 Systemic reactions: Pyrexia (Temperature) \>39.5˚C; Vomiting, ≥ 6 times per 24 hours or needing parenteral nutrition; Crying, \>3 hours; Somnolence, Sleeping often or difficulty waking; Anorexia, refuses ≥3 meals; and Irritability, Inconsolable.
Number of Participants Reporting a Solicited Injection Site Following Booster Vaccination With Prevenar Vaccine	Day 0 up to Day 7 after final booster vaccination	Solicited injection site: Pain, Erythema, Swelling, and Extensive swelling of vaccinated limb. Grade 3 Injection site: Pain, cries if limb is moved or reduced movement; Erythema and Swelling, ≥5 cm; and Extensive swelling of limb, Severe.
Summary of Geometric Mean Titers to Vaccine Antibodies Post Primary Vaccination Series; Before and After Booster Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine or Infanrix Hexa Vaccine.	Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination	Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-Tetanus, anti-PT, and anti-FHA antibodies were measured by ELISA. Anti-Poliovirus types 1, 2, and 3 were measured by neutralization assay. Anti-Hepatitis B antibodies were measured by the commercially available VITROS ECi/ECiQ Immunodiagnostic System. Anti-PRP antibodies were measured using a Farr type radioimmunoassay that used radiolabeled PRP (3H PRP) in the presence of 36Cl (volume marker).; Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers.