Safety & Immunogenicity of Pneumococcal Vaccine 2189242A Co-administered With DTPa-HBV-IPV/Hib in Healthy Infants

NCT01204658 | Completed Phase 2 Results

• 2 other identifiers: 1139942010-019730-27
• Study Type: interventional
• Target: 576
• Locations: 4 countries
• Sites: 24

Brief Summary

This study will assess the safety, reactogenicity and immunogenicity of two formulations of GSK Biologicals' pneumococcal vaccine 2189242A given as a 3-dose primary vaccination course during the first 6 months of life followed by a booster dose at 12-15 months of age and co-administered with DTPa-HBV-IPV/Hib vaccine.

Conditions

Infections, Streptococcal

Keywords

Haemophilus influenzae; Streptococcus pneumoniae; immunogenicity; Pneumococcal vaccine; infants; safety

Outcome Measures

Primary Outcomes (3)

• Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms Related to Vaccination - Primary Phase of the Study

  Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than or equal to \[\>=\] 38 degrees Celsius \[°C\]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 (G3) Drowsiness = Drowsiness that prevented normal activity. G3 Irritability = Crying that could not be comforted/prevented normal activity. G3 Loss of appetite = Subject did not eat at all. G3 Fever = Rectal temperature higher than (\>) 40.0°C. Primary results correspond to results for occurrences of G3 fever symptoms assessed by the investigators as related to vaccination (Related G3 fever).

  Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course

• Percentage of Subjects Reporting Fever > 40.0°C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in 10PP-LD/Infanrix Hexa Group and in Synflorix/Infanrix Hexa Group

  Grade 3 fever was defined as fever by rectal measurement \> 40.0°C. Related was defined as causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-LD/Infanrix hexa (or 10PP-LD) and Synflorix/Infanrix hexa (or 10PN) groups only.

  During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses

• Percentage of Subjects Reporting Fever > 40° C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in the 10PP-HD/Infanrix Hexa Group and in the Synflorix/Infanrix Hexa Group

  Grade 3 fever was defined as fever by rectal measurement \>40.0°C. Related was defined as causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-HD/Infanrix hexa (or 10PP-HD) and Synflorix/Infanrix hexa (or 10PN) groups only.

  During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses

Secondary Outcomes (26)

• Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Primary Phase of the Study

  At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

• Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Booster Phase of the Study

  At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

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

  At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

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

  At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

• Antibody Concentrations Against Pneumococcal Serotypes - Primary Phase of the Study

  At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

Study Arms (4)

10PP-LD/Infanrix hexa Group

EXPERIMENTAL

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of the GSK 2189242A (or 10PP) vaccine combined with low doses (LD) of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD) co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of the 10PP and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for the 10PP vaccine and on the right side for Infanrix hexa™.

Biological: Pneumococcal vaccine GSK 2189242A (LD formulation 1); Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

10PP-HD/Infanrix hexa Group

EXPERIMENTAL

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of the GSK 2189242A (or 10PP) vaccine combined with high doses (HD) of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD), co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of the 10PP and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for the 10PP vaccine and on the right side for Infanrix hexa™.

Biological: Pneumococcal vaccine GSK 2189242A (HD formulation 2); Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

Synflorix/Infanrix hexa Group

ACTIVE COMPARATOR

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of Synflorix™ vaccine, co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of Synflorix™ and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for Synflorix™ and on the right side for Infanrix hexa™.

Biological: Synflorix; Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

Prevnar 13/Infanrix hexa Group

ACTIVE COMPARATOR

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of Prevnar 13™ vaccine, co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of Prevnar 13™ and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for Prevnar 13™ and on the right side for Infanrix hexa™.

Biological: Prevenar 13; Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

Interventions

Pneumococcal vaccine GSK 2189242A (LD formulation 1) BIOLOGICAL

Intramuscular injection

Also known as: GSK 2189242A; 10PP-LD

10PP-LD/Infanrix hexa Group

Pneumococcal vaccine GSK 2189242A (HD formulation 2) BIOLOGICAL

Intramuscular injection

Also known as: GSK 2189242A; 10PP-HD

10PP-HD/Infanrix hexa Group

Synflorix BIOLOGICAL

Intramuscular injection

Synflorix/Infanrix hexa Group

Prevenar 13 BIOLOGICAL

Intramuscular injection

Prevnar 13/Infanrix hexa Group

Infanrix Hexa (DTPa-HBV-IPV/Hib) BIOLOGICAL

Intramuscular injection

10PP-HD/Infanrix hexa Group; 10PP-LD/Infanrix hexa Group; Prevnar 13/Infanrix hexa Group; Synflorix/Infanrix hexa Group

Eligibility Criteria

• Age: 6 Weeks - 14 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) (LAR) can and will comply with the requirements of the protocol
• Male or female between, and including, 6 and 14 weeks (42-104 days) of age at the time of the first vaccination.
• 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 36 to 42 weeks inclusive.

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 not foreseen by the study protocol during the study period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the exception of licensed flu 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 since birth.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• A family history of congenital or hereditary immunodeficiency.
• Major congenital defects or any chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease and/or fever at the time of enrolment.
• Fever is defined as temperature \>= 38.0°C on rectal setting or \>= 37.5°C on oral or axillary setting.
• 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 primary epoch and during the period starting three months before booster vaccination and ending one month after the booster vaccination.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (24)

GSK Investigational Site

Benešov, 256 01, Czechia

Location

GSK Investigational Site

Brno, 613 00, Czechia

Location

GSK Investigational Site

Děčín, 405 01, 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

Náchod, 547 01, Czechia

Location

GSK Investigational Site

Ostrov, 363 01, Czechia

Location

GSK Investigational Site

Pardubice, 532 03, Czechia

Location

GSK Investigational Site

Prague, 1600, Czechia

Location

GSK Investigational Site

Schwäbisch Hall, Baden-Wurttemberg, 74523, Germany

Location

GSK Investigational Site

Tuttlingen, Baden-Wurttemberg, 78532, Germany

Location

GSK Investigational Site

Detmold, North Rhine-Westphalia, 32756, Germany

Location

GSK Investigational Site

Frankenthal, Rhineland-Palatinate, 67227, Germany

Location

GSK Investigational Site

Berlin, 13055, Germany

Location

GSK Investigational Site

Dębica, 39-200, Poland

Location

GSK Investigational Site

Krakow, 31-503, Poland

Location

GSK Investigational Site

Poznan, 61-709, Poland

Location

GSK Investigational Site

Siemianowice Śląskie, 41-103, Poland

Location

GSK Investigational Site

Warsaw, 01-184, Poland

Location

GSK Investigational Site

Wroclaw, 50345, Poland

Location

GSK Investigational Site

Örebro, SE-702 11, Sweden

Location

GSK Investigational Site

Östersund, SE-831 83, Sweden

Location

GSK Investigational Site

Umeå, SE-901 85, Sweden

Location

Related Publications (1)

• Prymula R, Szenborn L, Silfverdal SA, Wysocki J, Albrecht P, Traskine M, Gardev A, Song Y, Borys D. Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: Results from a randomized phase II study in infants. Vaccine. 2017 Aug 16;35(35 Pt B):4603-4611. doi: 10.1016/j.vaccine.2017.07.008. Epub 2017 Jul 17.

  PMID: 28729019 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 17, 2010
• Study Start: September 27, 2010
• Primary Completion: November 3, 2011
• Study Completion: October 1, 2012
• Last Updated: May 29, 2019
• Results First Posted: September 28, 2016

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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 (10); DE (5); PL (6); SE (3)