Clinical trial NCT01545375: Evaluation of a Vaccine for Reducing Ear and Lung Infections in Children
Official title: Study to Determine Protective Efficacy Against Otitis Media and Assess Safety of an Investigational Pneumococcal Vaccine 2189242A in Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Streptococcal
Keywords: nasopharyngeal carriage
safety
immunogenicity
US
Pneumococcal vaccine
efficacy
Streptococcus pneumoniae
infants
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-03-06
Enrollment: 1806
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s) including latex.
* Major congenital defects or serious chronic illness.
* History of any neurological disorders or seizures.
* Acute disease and/or fever at the time of enrollment.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
* Any medical or social condition which might interfere with the assessment of the study objectives in the opinion of the investigator.

For infants in the Immuno/reacto subgroup only:

• Previous vaccination against H. influenzae type b.

Primary outcomes:
measure: Time to Occurrence of Any Acute Otitis Media (AOM) Diagnosed and Verified Against American Academic of Pediatrics (AAP) Criteria
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
Secondary outcomes:
measure: Time to Occurrence of Any Episodes of AOM Diagnosed by Healthcare-provider
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: Time to Occurrence of Any Clinical Acute Otitis Media (AOM) Diagnosed and Verified Against Modified American Academic of Pediatrics (AAP) Criteria
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: Number of Subjects With Any Recurrent Healthcare Provider Diagnosed Acute Otitis Media (AOM)
timeFrame: From the administration of dose 1 up to Month 22
measure: Time to Occurrence of Any Draining Acute Otitis Media (AOM)
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: Time to Occurrence of Any Draining Pneumococcal Acute Otitis Media (AOM)
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: Number of Subjects With Any Acute Otitis Media (AOM) With Temporally Related Carriage
timeFrame: From the administration of dose 1 up to Month 22
measure: Time to Occurrence of Medically Attended Acute Lower Respiratory Tract Infection (ALRI)
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: Time to Occurrence of Medically Attended ALRI With Fever Documented at the Visit or History of Fever Within 3 Days Preceding a Given Episode
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: 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.
timeFrame: Any time from 2 weeks after the administration of dose 3 up to Month 22
measure: Number of Subjects With S. Pneumoniae (Any and Serotype Specific) in the Nasopharynx - Carriage Sub-cohort
timeFrame: 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)
measure: Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (Ply) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Immuno/Reacto Sub-cohort
timeFrame: 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
measure: Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid (Ply) Haemolysis Activity, or Hem-Ply Antibodies
timeFrame: 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
measure: Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Immuno/Reacto Sub-cohort
timeFrame: 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)]
measure: Antibody Concentrations Against Vaccine Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F
timeFrame: 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)]
measure: Antibody Concentrations Against Vaccine-related Serotypes 6C
timeFrame: 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)]
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes
timeFrame: One month post-dose 3 [PIII(Month 5)] and one month post-booster dose [Post-booster(Month 11)]
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C
timeFrame: One month post-dose 3 [PIII(Month 5)] and one month post-booster dose [Post-booster(Month 11)]
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Primary Vaccination - Immuno/Reacto Sub-cohort
timeFrame: Within the 4-day (Days 0-3) post-primary vaccination period following each dose
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Booster Vaccination - Immuno/Reacto Sub-cohort
timeFrame: Within the 4-day (Days 0-3) post-booster vaccination period
measure: 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
timeFrame: Within the 4-day (Days 0-3) post-primary vaccination period following each dose
measure: 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
timeFrame: Within the 4-day (Days 0-3) post-booster vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) After Primary Vaccination - Immuno/Reacto Sub-cohort
timeFrame: Within the 31-day (Days 0-30) period post primary vaccination, across doses
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) After Booster Vaccination - Immuno/Reacto Sub-cohort
timeFrame: Within the 31-day (Days 0-30) period post booster vaccination
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: From Day 0 to Month 22
Other outcomes:
Locations:
city: Chinle
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fort Defiance
country: United States
facility: GSK Investigational Site
state: Arizona
city: Whiteriver
country: United States
facility: GSK Investigational Site
state: Arizona
city: Gallup
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Shiprock
country: United States
facility: GSK Investigational Site
state: New Mexico
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hammitt LL, Campbell JC, Borys D, Weatherholtz RC, Reid R, Goklish N, Moulton LH, Traskine M, Song Y, Swinnen K, Santosham M, O'Brien KL. Efficacy, safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: A phase IIb randomized study. Vaccine. 2019 Dec 3;37(51):7482-7492. doi: 10.1016/j.vaccine.2019.09.076. Epub 2019 Oct 16.