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

NCT01444781 | Completed Phase 3 Results DMC

• 2 other identifiers: A3L27U1111-1112-8473
• Study Type: interventional
• Target: 1,106
• Locations: 1 country
• Sites: 1

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.

Conditions

Diphtheria; Tetanus; Whooping Cough; Hepatitis B; Poliomyelitis

Keywords

Diphtheria; Tetanus; Whooping Cough; Hepatitis B; Poliomyelitis; Pediatric combined vaccine; Invasive Hib infections

Outcome Measures

Primary Outcomes (4)

• 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

  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

  Day 140 (Primary series) and Day 0 (Pre-booster)

• 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

  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.

  Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination

• 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

  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.

  Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination

• 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

  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.

  Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination

Secondary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Study Group 1

EXPERIMENTAL

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™

Biological: DTaP-IPV-Hep B-PRP~T combined vaccine + Pneumococcal polysaccharide

Study Group 2

ACTIVE COMPARATOR

Participants previously primed with DTaP-IPV-Hep B-PRP\~T, will receive one dose of Infanrix hexa™ vaccine + one dose of Prevenar™

Biological: DTaP-Hep B-IPV // Hib Vaccine + Pneumococcal polysaccharide

Study Group 3

EXPERIMENTAL

Participants previously primed with Infanrix hexa™ will receive one dose of DTaP-IPV-Hep B-PRP\~T + one dose of Prevenar™.

Biological: DTaP-IPV-Hep B-PRP~T + Pneumococcal polysaccharide vaccine

Interventions

DTaP-IPV-Hep B-PRP~T combined vaccine + Pneumococcal polysaccharide BIOLOGICAL

0.5 mL, Intramuscular each into the right and left deltoid muscle

Also known as: DTaP-IPV-Hep B-PRP~T vaccine, Prevenar™

Study Group 1

DTaP-Hep B-IPV // Hib Vaccine + Pneumococcal polysaccharide BIOLOGICAL

0.5 mL, Intramuscular each into the right and left deltoid muscle

Also known as: Infanrix hexa™, Prevenar™

Study Group 2

DTaP-IPV-Hep B-PRP~T + Pneumococcal polysaccharide vaccine BIOLOGICAL

0.5 mL (each), Intramuscular each into the right and left deltoid muscle

Also known as: DTaP-IPV-Hep B-PRP~T combined vaccine, Prevenar™

Study Group 3

Eligibility Criteria

• Age: 12 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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™).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (2)

Unknown Facility

Cali, Colombia

Location

Unknown Facility

San José, Costa Rica

Location

Related Links

• Related Info

MeSH Terms

Conditions

Diphtheria; Tetanus; Whooping Cough; Hepatitis B; Poliomyelitis

Interventions

Heptavalent Pneumococcal Conjugate Vaccine; HibTITER protein, Haemophilus influenzae; diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Clostridium Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined

Results Point of Contact

• Title: Medical Director
• Organization: Sanofi Pasteur Inc.

RegistryContactUs@sanofipasteur.com

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: October 3, 2011
• Study Start: September 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 16, 2014
• Results First Posted: July 16, 2014

Record last verified: 2014-07

Locations

CO (1)