Study to Determine Protective Efficacy Against Otitis Media and Assess Safety of an Investigational Pneumococcal Vaccine 2189242A in Healthy Infants
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Infections, Streptococcal
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1806
- Locations
- 1
- Primary Endpoint
- Time to Occurrence of Any Acute Otitis Media (AOM) Diagnosed and Verified Against American Academic of Pediatrics (AAP) Criteria
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to 1) demonstrate the protective efficacy against acute otitis media (AOM), 2) assess safety of the GlaxoSmithKline (GSK) Biologicals' pneumococcal vaccine GSK2189242A in Native American infants aged less than 24 months, living in the southwestern US, in and around the Navajo and White Mountain Apache reservations, and 3) evaluate the impact on acute lower respiratory tract infections (ALRI) up to the second year of life.
Detailed Description
The study will also evaluate the impact of the pneumococcal vaccine GSK2189242A on nasopharyngeal carriage in a subgroup of children called Carriage subgroup. Immunogenicity and reactogenicity of the pneumococcal vaccine GSK2189242A will be evaluated in another subgroup of children called Immuno/reacto subgroup. Protocol Posting has been updated following Protocol Amendment 3, April 2012, leading to the addition of a secondary outcome measure. Protocol Posting has been updated following Protocol Amendment 7, March 2017, to add serological testing for antibodies against the Hib polysaccharide PRP on samples collected 12 months following booster dose (Month 22) in the Immuno/reacto sub-cohort, in order to evaluate the long term persistence of immune responses to co-administered PedvaxHIB vaccine.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject who the investigator believes that their parent(s)/Legally Authorized Representative(s) (LARs) can and will comply with the requirements of the protocol.
- •A male or female American Indian infant between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
- •Voluntary, written informed consent obtained from the parents/LAR(s) of the subject. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by a witness.
- •Healthy subject as established by medical history and clinical examination before entering into the study.
- •Born after a gestation period of more than 35 6/7 weeks.
Exclusion Criteria
- •For all infants:
- •Child in care.
- •Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- •Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
- •Planned administration/administration of a vaccine not foreseen by the study protocol starting from 30 days before each dose and ending 30 days after each dose of study vaccines, with the exception of licensed inactivated influenza vaccines and recommended pediatric vaccines.
- •Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
- •Previous vaccination against S. pneumoniae.
- •Obstruction or anomalies of the nasopharyngeal space.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- •Family history of congenital or hereditary immunodeficiency.
Outcomes
Primary Outcomes
Time to Occurrence of Any Acute Otitis Media (AOM) Diagnosed and Verified Against American Academic of Pediatrics (AAP) Criteria
Time Frame: Any time from 2 weeks after the administration of dose 3 up to Month 22
Time to occurrence of any episode of AOM is expressed in terms of rate: Person-year rate = number of episodes (n)/sum of follow-up expressed in years (T\[year)\]). Definition of clinical AOM diagnosed and verified against AAP criteria required meeting three criteria based on the guidelines from the AAP \[AAP, 2004\], as per the judgment of a treating physician or equivalent licensed medical professional: A history of acute (recent, usually abrupt) onset of signs and symptoms of middle-ear inflammation and middle-ear effusion (MEE).AND The presence of MEE indicated by any of the following: a) Bulging of tympanic membrane; b) Limited or absent mobility of tympanic membrane; c) Air-fluid level behind tympanic membrane; d) Otorrhea AND Signs or symptoms of middle-ear inflammation as indicated by either: a) Distinct erythema of tympanic membrane or b) Distinct otalgia (discomfort clearly referable to the ear\[s\] that resulted in interference with or precluded normal activity or sleep).
Secondary Outcomes
- Number of Subjects With Any Recurrent Healthcare Provider Diagnosed Acute Otitis Media (AOM)(From the administration of dose 1 up to Month 22)
- Number of Subjects With Any Acute Otitis Media (AOM) With Temporally Related Carriage(From the administration of dose 1 up to Month 22)
- Time to Occurrence of Any Draining Pneumococcal Acute Otitis Media (AOM)(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Time to Occurrence of Any Medically Attended Healthcare-provider-diagnosed ALRI With Fever Documented at the Visit or History of Fever Within 3 Days Preceding a Given Episode.(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Immuno/Reacto Sub-cohort(1 month post-dose 3 [PIII(Month 5)], prior to booster dose [PIII(Month 10)], 1 month post-booster dose [Post-booster(Month 11)], 12 months post-booster dose [Post-booster(Month 22)])
- Number of Subjects With Any Unsolicited Adverse Events (AEs) After Booster Vaccination - Immuno/Reacto Sub-cohort(Within the 31-day (Days 0-30) period post booster vaccination)
- Time to Occurrence of Any Episodes of AOM Diagnosed by Healthcare-provider(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Time to Occurrence of Any Clinical Acute Otitis Media (AOM) Diagnosed and Verified Against Modified American Academic of Pediatrics (AAP) Criteria(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Time to Occurrence of Any Draining Acute Otitis Media (AOM)(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Time to Occurrence of Medically Attended ALRI With Fever Documented at the Visit or History of Fever Within 3 Days Preceding a Given Episode(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Number of Subjects With S. Pneumoniae (Any and Serotype Specific) in the Nasopharynx - Carriage Sub-cohort(At 7 months of age (Month 5), 12-15 months of age (Month 10),18-22 months of age (Month 16) and 24-27 months of age (Month 22))
- Antibody Concentrations Against Vaccine-related Serotypes 6C(One month post-dose 3 [PIII(Month 5)], prior to booster dose [PIII(Month 10)] and one month post-booster dose [Post-booster(Month 11)])
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Primary Vaccination - Immuno/Reacto Sub-cohort(Within the 4-day (Days 0-3) post-primary vaccination period following each dose)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Booster Vaccination - Immuno/Reacto Sub-cohort(Within the 4-day (Days 0-3) post-booster vaccination period)
- Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (Ply) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Immuno/Reacto Sub-cohort(One month post-dose 3 [PIII(Month 5)], prior to booster dose [PIII(Month 10)] and one and twelve months post-booster dose [Post-booster(Month 11) and Post-booster(Month 22)], respectively)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes(One month post-dose 3 [PIII(Month 5)] and one month post-booster dose [Post-booster(Month 11)])
- Time to Occurrence of Medically Attended Acute Lower Respiratory Tract Infection (ALRI)(Any time from 2 weeks after the administration of dose 3 up to Month 22)
- Antibody Concentrations Against Vaccine Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F(One month post-dose 3 [PIII(Month 5)], prior to booster dose [PIII(Month 10)] and one month post-booster dose [Post-booster(Month 11)])
- Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid (Ply) Haemolysis Activity, or Hem-Ply Antibodies(One month post-dose 3 [PIII(Month 5)], prior to booster dose [PIII(Month 10)] and one and twelve months post-booster dose [Post-booster(Month 11) and Post-booster(Month 22)], respectively)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C(One month post-dose 3 [PIII(Month 5)] and one month post-booster dose [Post-booster(Month 11)])
- Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, After Primary Vaccination - Immuno/Reacto Sub-cohort(Within the 4-day (Days 0-3) post-primary vaccination period following each dose)
- Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, After Booster Vaccination - Immuno/Reacto Sub-cohort(Within the 4-day (Days 0-3) post-booster vaccination period)
- Number of Subjects With Any Unsolicited Adverse Events (AEs) After Primary Vaccination - Immuno/Reacto Sub-cohort(Within the 31-day (Days 0-30) period post primary vaccination, across doses)
- Number of Subjects With Any Serious Adverse Events (SAEs)(From Day 0 to Month 22)