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

NCT01616459 | Completed Phase 2 Results

• 2 other identifiers: 1164852011-005743-27
• Study Type: interventional
• Target: 953
• Locations: 4 countries
• Sites: 42

Brief 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.

Conditions

Infections, Streptococcal

Keywords

Streptococcus pneumoniae; Haemophilus influenzae; Pneumococcal vaccine; Infants; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (5)

• 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

• 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)

• 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)

• 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)

• 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 Outcomes (20)

• Antibody Concentrations Against Pneumococcal Serotypes During the Booster Phase of the Study

  At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

• Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Primary Phase of the Study

  At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine

• Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Booster Phase of the Study

  At study Month 11, e.g.: at one month post booster vaccination with pneumococcal vaccine

• Concentrations of Antibodies Against Protein D (Anti-PD) During the Primary Phase of the Study

  At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine

• Concentrations of Antibodies Against Protein D (Anti-PD) During the Booster Phase of the Study

  At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

Study Arms (4)

11Pn Group

EXPERIMENTAL

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830929A, or 11Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 11Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Biological: Pneumococcal conjugate vaccine GSK2830929A; Biological: Infanrix hexa™

12Pn Group

EXPERIMENTAL

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Biological: Pneumococcal conjugate vaccine GSK2830930A; Biological: Infanrix hexa™

Synflorix Group

ACTIVE COMPARATOR

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Synflorix™ at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Synflorix™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Synflorix™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).

Biological: Synflorix™; Biological: Infanrix hexa™

Prevnar13 Group

ACTIVE COMPARATOR

Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Prevnar13™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Prevnar13™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Prevnar13™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate ).

Biological: Prevnar 13™; Biological: Infanrix hexa™

Interventions

Pneumococcal conjugate vaccine GSK2830929A BIOLOGICAL

Intramuscular injection

11Pn Group

Pneumococcal conjugate vaccine GSK2830930A BIOLOGICAL

Intramuscular injection

12Pn Group

Synflorix™ BIOLOGICAL

Intramuscular injection

Synflorix Group

Prevnar 13™ BIOLOGICAL

Intramuscular injection

Prevnar13 Group

Infanrix hexa™ BIOLOGICAL

Intramuscular injection

11Pn Group; 12Pn Group; Prevnar13 Group; Synflorix Group

Eligibility Criteria

• Age: 6 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (42)

GSK Investigational Site

Benešov, 256 01, Czechia

Location

GSK Investigational Site

Děčín, 405 01, Czechia

Location

GSK Investigational Site

Domažlice, 34401, Czechia

Location

GSK Investigational Site

Jindřichův Hradec, 37701, Czechia

Location

GSK Investigational Site

Kladno, 272 01, Czechia

Location

GSK Investigational Site

Liberec, 46015, Czechia

Location

GSK Investigational Site

Lipník nad Bečvou, 75131, Czechia

Location

GSK Investigational Site

Náchod, 547 01, Czechia

Location

GSK Investigational Site

Ostrava - Poruba, 70800, Czechia

Location

GSK Investigational Site

Ostrov, 363 01, Czechia

Location

GSK Investigational Site

Pardubice, 532 03, Czechia

Location

GSK Investigational Site

Pilsen, 305 99, Czechia

Location

GSK Investigational Site

Prague, 1600, Czechia

Location

GSK Investigational Site

Kehl, Baden-Wurttemberg, 77694, Germany

Location

GSK Investigational Site

Schwäbisch Hall, Baden-Wurttemberg, 74523, Germany

Location

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70469, Germany

Location

GSK Investigational Site

Berchtesgaden, Bavaria, 83471, Germany

Location

GSK Investigational Site

Kirchheim, Bavaria, 85551, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81241, Germany

Location

GSK Investigational Site

Olching, Bavaria, 82140, Germany

Location

GSK Investigational Site

Detmold, North Rhine-Westphalia, 32756, Germany

Location

GSK Investigational Site

Kleve-Materborn, North Rhine-Westphalia, 47533, Germany

Location

GSK Investigational Site

Löhne, North Rhine-Westphalia, 32584, Germany

Location

GSK Investigational Site

Frankenthal, Rhineland-Palatinate, 67227, Germany

Location

GSK Investigational Site

Trier, Rhineland-Palatinate, 54290, Germany

Location

GSK Investigational Site

Wanzleben, Saxony-Anhalt, 39164, Germany

Location

GSK Investigational Site

Flensburg, Schleswig-Holstein, 24937, Germany

Location

GSK Investigational Site

Berlin, 13055, Germany

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GSK Investigational Site

Berlin, 14197, Germany

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GSK Investigational Site

Dębica, 39-200, Poland

Location

GSK Investigational Site

Oleśnica, 56-400, Poland

Location

GSK Investigational Site

Siemianowice Śląskie, 41-103, Poland

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GSK Investigational Site

Torun, 87-100, Poland

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GSK Investigational Site

Trzebnica, 55-100, Poland

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GSK Investigational Site

Warsaw, 01-809, Poland

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GSK Investigational Site

Wroclaw, 50345, Poland

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GSK Investigational Site

Almería, 04009, Spain

Location

GSK Investigational Site

Antequera/Málaga, 29200, Spain

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GSK Investigational Site

Burgos, 09006, Spain

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GSK Investigational Site

Seville, 41014, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Valladolid, 47012, Spain

Location

Related 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.

  PMID: 30054160 BACKGROUND

MeSH Terms

Conditions

Streptococcal Infections; Haemophilus Infections

Interventions

PHiD-CV vaccine; 13-valent pneumococcal vaccine; diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pasteurellaceae Infections; Gram-Negative Bacterial Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2012
• First Posted: June 11, 2012
• Study Start: July 11, 2012
• Primary Completion: April 25, 2013
• Study Completion: January 22, 2014
• Last Updated: July 16, 2019
• Results First Posted: June 16, 2014

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months

Locations

CZ (13); ES (6); PL (7); DE (16)