Immunogenicity and Safety of Two Formulations of GSK Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants

Infections, Streptococcal Clinical Trial

Official title:

Immunogenicity and Safety Study of Two Formulations of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01616459
• Other study ID #: 116485
• Secondary ID: 2011-005743-27
• Status: Completed
• Phase: Phase 2
• Start date: July 11, 2012
• Est. completion date: January 22, 2014

Study information

• Verified date: July 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the immunogenicity, reactogenicity and safety of two formulations of GSK Biologicals' pneumococcal vaccine (2830929A and 2830930A) administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine will be co-administered in infants with the pneumococcal study vaccines.

Description:

The purpose of this study is to assess the immunogenicity of the two formulations of GSK Biologicals' pneumococcal vaccine 2830929A (11-valent vaccine or 11Pn vaccine) and 2830930A (12-valent vaccine or 12Pn vaccine), when administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life, when compared to immune responses to the licensed vaccines Synflorix™ and Prevnar 13™, and to assess the reactogenicity and safety of these two same investigational formulations when administered according to this schedule. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa™) vaccine will be co-administered in infants with the pneumococcal study vaccines.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 953
• Est. completion date: January 22, 2014
• Est. primary completion date: April 25, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 12 Weeks

Eligibility

Inclusion Criteria:

• Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LARs) can and will comply with the requirements of the protocol.

• A male or female between, and including 6 to 12 weeks (42-90 days) of age at the time of the first vaccination. In addition, the first pneumococcal and DTPa-HBV-IPV/Hib vaccination should be given in accordance with the official national recommendations for the immunisation schedule of infants.

• Written informed consent obtained from the parents/LAR(s) of the subject.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Born after a gestation period of at least 36 weeks.

Exclusion Criteria:

• 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 containing diphtheria toxoid, tetanus toxoid (except MenC-TT in Spain) or CRM197 and not foreseen by the study protocol during any time of the study period, or of any other vaccines not foreseen by the protocol in the period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the following exceptions:

• Licensed influenza vaccines are always allowed, even if concomitantly administered with the study vaccines.

• Licensed rotavirus vaccines are allowed if administered at least 7 days before or after each dose of study of vaccines.

• Licensed MenC-TT vaccine is allowed in Spain and should be concomitantly administered with the study vaccine at around 2, 4 and 12-15 months of age.

• In case an emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is organised by the public health authorities, outside the routine immunization program, that vaccine can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental recommendations.

• 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 .

• 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).

• Major congenital defects or serious chronic illness, including Kawasaki's syndrome.

• History of any neurological disorders or seizures, including conditions such as hypotensive-hyporesponsive episodes, encephalopathy and any convulsions (afebrile and febrile).

• Acute disease and/or fever at the time of enrolment.

• Administration of immunoglobulins and/or any blood products since birth or planned administration during study period.

• Previous vaccination against diphtheria, tetanus, pertussis, polio, H. influenzae type b.

• Previous vaccination against S. pneumoniae.

• History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, H. influenzae type b disease.

• Any medical condition which might interfere with the assessment of the study objectives in the opinion of the investigator.

Related Conditions & MeSH terms

• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• Pneumococcal conjugate vaccine GSK2830929A
Intramuscular injection
• Pneumococcal conjugate vaccine GSK2830930A
Intramuscular injection
• Synflorix™
Intramuscular injection
• Prevnar 13™
Intramuscular injection
• Infanrix hexa™
Intramuscular injection

Locations

Country	Name	City	State
Czechia	GSK Investigational Site	Benesov
Czechia	GSK Investigational Site	Decin
Czechia	GSK Investigational Site	Domazlice
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Kladno
Czechia	GSK Investigational Site	Liberec
Czechia	GSK Investigational Site	Lipnik nad Becvou
Czechia	GSK Investigational Site	Nachod
Czechia	GSK Investigational Site	Ostrava - Poruba
Czechia	GSK Investigational Site	Ostrov
Czechia	GSK Investigational Site	Pardubice
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Praha 6
Germany	GSK Investigational Site	Berchtesgaden	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Detmold	Nordrhein-Westfalen
Germany	GSK Investigational Site	Flensburg	Schleswig-Holstein
Germany	GSK Investigational Site	Frankenthal	Rheinland-Pfalz
Germany	GSK Investigational Site	Kehl	Baden-Wuerttemberg
Germany	GSK Investigational Site	Kirchheim	Bayern
Germany	GSK Investigational Site	Kleve-Materborn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Loehne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Olching	Bayern
Germany	GSK Investigational Site	Schwaebisch-Hall	Baden-Wuerttemberg
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Trier	Rheinland-Pfalz
Germany	GSK Investigational Site	Wanzleben	Sachsen-Anhalt
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Olesnica
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Trzebnica
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Spain	GSK Investigational Site	Almería
Spain	GSK Investigational Site	Antequera/Málaga
Spain	GSK Investigational Site	Burgos
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valladolid

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Czechia,  Germany,  Poland,  Spain, 

References & Publications (1)

Carmona Martinez A, Prymula R, Miranda Valdivieso M, Otero Reigada MDC, Merino Arribas JM, Brzostek J, Szenborn L, Ruzkova R, Horn MR, Jackowska T, Centeno-Malfaz F, Traskine M, Dobbelaere K, Borys D. Immunogenicity and safety of 11- and 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccines (11vPHiD-CV, 12vPHiD-CV) in infants: Results from a phase II, randomised, multicentre study. Vaccine. 2019 Jan 3;37(1):176-186. doi: 10.1016/j.vaccine.2018.07.023. Epub 2018 Jul 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody Concentrations Against Pneumococcal Serotypes During the Primary Phase of the Study	Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (=) 0.05 µg/mL. Primary outcome results correspond to antibody concentrations for all serotypes presented at the exception of those for the antibodies against the cross-reactive pneumococcal serotype 3 (ANTI-3).	At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Primary	Percentage (%) of Subjects (Synflorix and 11Pn Groups) With Antibody Concentration = 0.2 µg/mL for Pneumococcal Serotypes	N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations = 0.2 µg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).	1 month post-dose 3 (primary phase)
Primary	Percentage (%) of Subjects (Prevnar13 and 11Pn Groups) With Antibody Concentration = 0.2 µg/mL for Anti-19A Pneumococcal Serotype	N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations = 0.2 µg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 19A (ANTI-19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).	1 month post-dose 3 (primary phase)
Primary	Percentage (%) of Subjects (Synflorix and 12Pn Groups) With Antibody Concentration = 0.2 µg/mL for Pneumococcal Serotypes	N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations = 0.2 µg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).	1 month post-dose 3 (primary phase)
Primary	Percentage (%) of Subjects (Prevnar13 and 12Pn Groups) With Antibody Concentration = 0.2 µg/mL for Anti-6A and 19A Pneumococcal Serotypes	N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations = 0.2 µg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 6A and 19A (ANTI-6A and 19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).	1 month post-dose 3 (primary phase)
Secondary	Antibody Concentrations Against Pneumococcal Serotypes During the Booster Phase of the Study	Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (=) 0.05 µg/mL. Analysis of concentrations of antibodies against the cross-reactive pneumococcal serotype 6C (ANTI-6C) will not be performed due to unavailability of a specific qualified assay.	At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
Secondary	Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Primary Phase of the Study	Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (=) 8. Testing for opsonophagocytic activity against the cross-reactive pneumococcal serotype 6C will not be performed due to unavailability of a specific qualified assay.	At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Secondary	Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Booster Phase of the Study	Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (=) 8. Testing for opsonophagocytic activity against the cross-reactive pneumococcal serotype 6C will not be performed due to unavailability of a specific qualified assay.	At study Month 11, e.g.: at one month post booster vaccination with pneumococcal vaccine
Secondary	Concentrations of Antibodies Against Protein D (Anti-PD) During the Primary Phase of the Study	Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The cut-off of the assay was an anti-PD antibody concentration higher than or equal to (=) 100 EL.U/mL.	At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Secondary	Concentrations of Antibodies Against Protein D (Anti-PD) During the Booster Phase of the Study	Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The cut-off of the assay was an anti-PD antibody concentration higher than or equal to (=) 100 EL.U/mL.	At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Primary Phase	Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm).	Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Booster Phase of the Study	Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm).	Within the 4-day (Days 0-3) period after booster vaccination
Secondary	Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Primary Phase of the Study	Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [=] 38.0 degrees Celsius [°C]),. Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C.	Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).
Secondary	Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Booster Phase of the Study	Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [=] 38.0 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C.	Within the 4-day (Days 0-3) period after booster vaccination
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Primary Phase of the Study	An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.	Within the 31-day (Days 0-30) period post primary vaccination, across doses
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Booster Phase of the Study	An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.	Within the 31-day (Days 0-30) period post booster vaccination
Secondary	Number of Subjects With Any Serious Adverse Events (SAEs)During the Primary Phase of the Study	A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.	From Month 0 to Month 3
Secondary	Number of Subjects With Any Serious Adverse Events (SAEs) During the Entire Duration of the Study	A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.	From Day 0 to Month 11
Secondary	Antibody Concentrations Against Pneumococcal Serotype 6A During the Booster Phase of the Study	Antibodies assessed for this outcome measure was that against the cross-reactive pneumococcal serotype 6A (ANTI-6A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (=) 0.05 µg/mL.	At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
Secondary	Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Primary Phase of the Study	Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 19A (OPA-19A). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (=) serotype-specific Lower Limit of Quantification (143).	At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Secondary	Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Booster Phase of the Study	Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 19A (OPA-19A). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (=) serotype-specific Lower Limit of Quantification (143).	At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine
Secondary	Antibody Concentrations Against Pneumococcal Serotype 6C During the Primary Phase of the Study.	No analysis was performed on Enzyme-Linked ImmunoSorbent Assay (ELISA) testing for antibody concentrations against vaccine serotype 6C as no specific qualified/validated assay was available.	At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Secondary	Antibody Concentrations Against Pneumococcal Serotype 6C During the Booster Phase of the Study.	No analysis was performed on Enzyme-Linked ImmunoSorbent Assay (ELISA) testing for antibody concentrations against vaccine serotype 6C as no specific qualified/validated assay was available.	At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
Secondary	Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Primary Phase of the Study	No analysis was performed on opsonophagocytic activity for antibody titers against vaccine serotype 6C as no specific qualified/validated assay was available.	At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Secondary	Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Booster Phase of the Study	No analysis was performed on opsonophagocytic activity for antibody titers against vaccine serotype 6C as no specific qualified/validated assay was available.	At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine