Study to Evaluate the Safety and Immunogenicity of a 10-valent Pneumococcal Conjugate Vaccine in Preterm Infants

Infections, Streptococcal Clinical Trial

Official title:

Study to Assess the Safety and Immunogenicity of GSK Biologicals 10-valent Pneumococcal Conjugate Vaccine When Co-administered With DTPa-HBV-IPV/Hib (Infanrix-Hexa) Vaccine in Preterm Infants as a 3-dose Primary Immunization Course During the First 6 Months of Life.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00390910
• Other study ID #: 107737
• Status: Completed
• Phase: Phase 3
• Start date: October 1, 2006
• Est. completion date: May 2, 2008

Study information

• Verified date: May 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the safety, reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals´ 10-valent pneumococcal conjugate vaccine when co-administered with diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated polio virus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine in preterm infants as a 3-dose primary immunization course during the first 6 months of life.

This protocol posting deals with objectives & outcome measures of the primary study. The objectives & outcome measures of the Booster study are presented in a separate protocol posting (NCT number = 00609492)

Description:

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 286
• Est. completion date: May 2, 2008
• Est. primary completion date: July 2, 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Weeks to 16 Weeks

Eligibility

Inclusion Criteria:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol

• A male or female between, and including, 8-16 weeks (56-118 days) of age at the time of the first vaccination.

• Written informed consent obtained from the parent or guardian of the subject.

• Born after a gestation period of >27 weeks (at least 189 days).

• If full term born, healthy subjects as established by medical history and clinical examination before entering into the study

• If premature, medically stable condition (not requiring significant medical support or ongoing management for debilitating disease and having demonstrated a clinical course of sustained recovery).

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccines, or planned use during the study period

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs from birth to the first vaccine dose.

• Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting from one month before the first dose of vaccines and up to Visit 6.

• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, Neisseria meningitidis and/or Streptococcus pneumoniae with the exception of vaccines where the first dose can be given within the first two weeks of life according to the national recommendations

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

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.

• History of any neurologic disorders or seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past).

• Acute disease at the time of enrolment.

• 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 serious chronic illness.

• Administration of immunoglobulins, with the exception of monoclonal antibodies against RSV, and/or any blood products within one month preceding the first dose of study vaccines or planned administration during the active phase of the study.

Related Conditions & MeSH terms

• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection, 3 doses
• Infanrix hexa
Intramuscular injection, 3 doses

Locations

Country	Name	City	State
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Rio/Patras
Greece	GSK Investigational Site	Thessaloniki
Spain	GSK Investigational Site	Burgos
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Móstoles/Madrid

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Greece,  Spain, 

References & Publications (3)

Omeñaca F, Merino JM, Tejedor JC, Constantopoulos A, Papaevangelou V, Kafetzis D, Tsirka A, Athanassiadou F, Anagnostakou M, François N, Borys D, Schuerman L. Immunization of preterm infants with 10-valent pneumococcal conjugate vaccine. Pediatrics. 2011 Aug;128(2):e290-8. doi: 10.1542/peds.2010-1184. Epub 2011 Jul 4. — View Citation

Omeneca F et al. Immunogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) following primary and booster vaccination in preterm-born children. Abstract presented at Excellence In Paediatrics. Florence, Italy, 3-6 December 2009.

Omeneca F et al. Vaccination of pre-term infants with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHID-CV). Abstract presented at the 27th annual ESPID meeting, Brussels, Belgium, 9-13 June 2009.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off	Fever was measured as rectal temperature. Assessment of occurrences of fever > 39.0 °C was performed post doses 1, 2 and 3 of Synflorix or Infanrix hexa vaccine.	Within 4 days (Days 0-3) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed included pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (>) 30 millimeters (mm). "Any" was defined as incidence of the specified symptom regardless of intensity.	Within 4 days (Days 0-3) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4)
Secondary	Number of Subjects With Any and Grade 3 Solicited General Symptoms	Solicited general symptoms assessed included drowsiness, fever (defined as rectal temperature = 38.0°C), irritability, and loss of appetite. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. "Any" was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination.	Within 4 days (Days 0-3) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4)
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs)	An AE is 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. "Any" was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	Within 31 days (Days 0-30) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4)
Secondary	Number of Subjects With Any Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity.	Throughout the active phase of the study (from the first vaccine administration (Month 0) up to 1 month after the third vaccine administration (Month5).
Secondary	Number of Subjects With Any Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity.	Throughout the entire study period starting from the first vaccine dose administration (Month 0) up to the end of the 6-month safety follow-up (ESFU- Month 10).
Secondary	Number of Subjects With Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Greater Than or Equal to (=) the Cut-off	The cut-off for the assay was = 0.20 microgram per mililiter (µg/ mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F = the Cut-off	The cut-off for the assay was = 0.05 microgram per mililiter (µg/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations = 0.05 microgram per milliliter (µg/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F = the Cut-off	The cut-off for the assay was = 8	One month after the 3rd vaccine dose (Month 5)
Secondary	Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F = 8.	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A = the Cut-off	The cut-off for the assay was = 0.05 microgram per milliliter (µg/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A	Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations = 0.05 microgram per milliliter (µg/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A = the Cut-off	The cut-off for the assay was = 8.	One month after the 3rd vaccine dose (Month 5)
Secondary	Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A	Seropositivity status was defined as opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A = 8.	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Concentrations of Antibodies Against Protein D (Anti-PD) = the Cut-off	The cut-off for the assay was = 100 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Concentrations of Antibodies Against Protein D (Anti-PD)	Seropositivity status was defined as anti-PD antibody concentrations = 100 ELISA units per milliliter ( EL.U/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Anti-diphtheria (Anti DT) and Anti-tetanus Toxoids (Anti TT) Antibody Concentrations = the Cut-off	The cut-off for the assay was = 0.1 international units per milliliter (IU/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Antibody Concentrations for Anti-diphtheria and Tetanus Toxoids = the Cut-off	Seroprotection status was defined as anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations = 0.1 IU/mL	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration = the Cut-off	The cut-off for the assay was = 0.15 microgram per milliliter (µg/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration = the Cut-off	The cut-off for the assay was = 1.0 microgram per milliliter (µg/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations = th Cut-off	Seroprotection status was defined as anti-PRP antibody concentrations = 0.15 µg/mL and = 1.0 µg/mL	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations = the Cut-off	The cut-off for the assay was = 5 ELISA unit per milliliter (EL.U/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Antibody Concentration for Anti-pertussis Toxoid (Anti-PT) , Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)	Seropositivity status was defined as anti-PT, anti-FHA, anti-PRN antibody concentrations = 5 EL.U/mL.	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations = the Cut-off.	The cut-off for the assay was = 10 milli-international units per milliliter (mIU/mL).	One month after the 3rd vaccine dose (Month 5)
Secondary	Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	Seroprotection status was defined as Anti-HBs antibody concentrations = 10 mIU/mL	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Titres	The cut-off for the assay was = 8.	One month after the 3rd vaccine dose (Month 5)
Secondary	Antibody Titers for Polio Type 1, 2 and 3 = the Cut-off	Seroprotection status was defined as Anti-polio type 1, Anti-polio type 2 and Anti-polio type 3 antibody titers = 8.	One month after the 3rd vaccine dose (Month 5)
Secondary	Number of Subjects With Vaccine Response to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)	Vaccine response to PT, FHA and PRN was defined as appearance of antibodies in subjects who are initially seronegative (S-), or at least maintenance of pre-vaccination antibody concentrations in those who are initially seropositive (S+). For the SYNFLORIX™ + INFANRIX™ HEXA GROUP I, no subjects presented initial seropositivity for PT and PRN antigens.	One month after the 3rd vaccine dose (Month 5)

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