Clinical trial NCT02447432: A Study to Compare the Immunogenicity of GSK Biologicals' 10Pn-PD-DiT 4-dose Presentation to the Licensed 1-dose Synflorix™ (10Pn-PD-DiT) Vaccine When Co-administered With DTPw-combination Vaccine in Healthy Infants
Official title: Study to Compare Immunogenicity of GSK Biologicals' 10Pn-PD-DiT 4-dose Presentation to the Licensed Synflorix™ (10Pn-PD-DiT) Vaccine When Co-administered With DTPw-combination Vaccine in Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Invasive disease by Streptococcus pneumoniae (S. pneumoniae) (including sepsis, meningitis, pneumonia, bacteraemia and acute otitis media)
Infants
Multidose
Haemophilus influenzae
Streptococcus pneumoniae
Preservative
Safety
Pneumonia
Immunogenicity
Pneumococcal conjugate vaccine
Acute otitis media caused by non-typeable Haemophilus influenzae (NTHi).
Respiratory tract infections
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-05-18
Enrollment: 320
Sex: ALL
Minimum age (years): 42
Maximum age (years): 76
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary aim of the study is to demonstrate that an investigational 4-dose presentation of the 10Pn-PD-DiT vaccine with preservative is non-inferior to the licensed presentation of Synflorix (preservative-free) in terms of immune responses to the 10 vaccine pneumococcal serotypes (primary objective) and to the vaccine-related pneumococcal serotype 19A (first secondary objective), after administration of a 3-dose primary vaccination course at 6, 10 and 18 weeks of age co-administered with the first 2 doses of DTPw-HBV/Hib vaccine given at 6, 10 and 14 weeks of age (according to the Expanded Program on Immunization (EPI) schedule).

In addition, the study will also assess the safety, reactogenicity, immunogenicity and antibody persistence (approximately 7 months following primary vaccination) of the 4-dose presentation of the 10Pn-PD-DiT vaccine given as primary vaccination schedule at 6, 10 and 18 weeks of age followed by a booster dose at 38 weeks.

This study also aims at assessing the safety, reactogenicity and immunogenicity of the 4-dose presentation of the 10Pn-PD-DiT vaccine when given as a booster dose at approximately 9 months of age.


Eligibility criteria: Inclusion Criteria:

* Subjects for whom, in the opinion of the investigator, the parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol (e.g., return for vaccination and follow-up visits).
* A male or female between, and including 6-10 weeks (42-76 days) of age at the time of the first vaccination.
* Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the subject. For all subjects, the consent form should be countersigned by a witness.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Born full-term (i.e., after a gestation period from 37 to 42 weeks).

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product (drug or vaccine) 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 (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. Inhaled and topical steroids are allowed.
* Planned administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab).
* Administration or planned administration of a vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of study vaccines and ending 30 days after with the following exceptions:
* 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 vaccine/product
* Previous vaccination against diphtheria, tetanus, pertussis, H. influenzae type b and/or S. pneumoniae.
* History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, and H. influenzae type b disease.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Family history of congenital or hereditary immunodeficiency.
* Major congenital defects or serious chronic illness.
* History of any neurological disorders or seizures.
* Acute disease and/or fever at the time of enrolment.
* Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C on rectal route. The preferred route for recording temperature in this study will be axillary.
* Subjects with a minor illness without fever may, be enrolled at the discretion of the investigator.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period (Hepatitis B immunoglobulins at birth are allowed).
* Any medical condition which might interfere with the assessment of the study objectives in the opinion of the investigator.

Primary outcomes:
measure: Antibody Concentrations Against Pneumococcal Serotypes (Epoch 001)
timeFrame: At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine
Secondary outcomes:
measure: Antibody Concentrations Against Pneumococcal Serotypes (Epoch 002)
timeFrame: At Month 8 and Month 9, e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes (Epoch 001)
timeFrame: At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes (Epoch 002)
timeFrame: At study Month 8 and Month 9, e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
measure: Concentrations of Antibodies Against Protein D (Anti-PD) (Epoch 001)
timeFrame: At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Concentrations of Antibodies Against Protein D (Anti-PD) (Epoch 002)
timeFrame: At study Month 9, e.g.: at one month post booster vaccination with pneumococcal vaccine
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms (Epoch 001)
timeFrame: Within the 4-day (Days 0-3) post-vaccination period following each primary dose of 10Pn-PD-DiTvaccine
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms (Epoch 002)
timeFrame: Within the 4-day (Days 0-3) period after booster vaccination
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination(Epoch 001)
timeFrame: Within the 4-day (Days 0-3) post-vaccination period following each primary dose of 10Pn-PD-DiTvaccine
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination (Epoch 002)
timeFrame: Within the 4-day (Days 0-3) period after booster vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) (Epoch 001)
timeFrame: Within the 31-day (Days 0-30) period post primary vaccination, across doses
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) (Epoch 002)
timeFrame: Within the 31-day (Days 0-30) period post booster vaccination
measure: Number of Subjects With Any Serious Adverse Events (SAEs) (Epoch 001)
timeFrame: From Month 0 to Month 4
measure: Number of Subjects With Any Serious Adverse Events (SAEs) During the Entire Duration of the Study
timeFrame: From Day 0 to Month 9
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Zaman K, Zaman SF, Zaman F, Aziz A, Faisal SB, Traskine M, Habib MA, Ruiz-Guinazu J, Borys D. Immunologic non-inferiority and safety of the investigational pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) 4-dose vial presentation compared to the licensed PHiD-CV 1-dose vial presentation in infants: A phase III randomized study. Vaccine. 2018 Jan 29;36(5):698-706. doi: 10.1016/j.vaccine.2017.12.034. Epub 2017 Dec 23.