Safety & Immunogenicity of 1 Dose of GSK134612 in Children 12-14 Months and 3-5 Years Old

Infections, Meningococcal Clinical Trial

Official title:

Evaluate the Immunogenicity, Reactogenicity, Safety of 4 Different Formulations of GSK Biologicals' Conjugate Vaccine (MenACWY) vs 1 Dose of MenC-CRM197 or Mencevax™ ACWY in Children Aged 12-14 Months & 3-5 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00196976
• Other study ID #: 103533
• Secondary ID: 103534
• Status: Completed
• Phase: Phase 2
• Start date: March 24, 2005
• Est. completion date: March 3, 2006

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of one dose of four different formulations of the MenACWY conjugate vaccine when given to healthy children aged 12-14 months and 3-5 years. The selection of the best formulation will be based on data obtained up to one month after the vaccine dose.

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

Description:

The study will enrol subjects of 12 to 14 months of age and subjects of 3 to 5 years of age. 3 formulations of GSK's MenACWY conjugate vaccine will be administered in a double-blind manner, while the 4th one will be single-blinded. Administration of the candidate vaccine or the active controls (MenC-CRM197 or Mencevax™ ACWY) will be done in an open manner. The study will be conducted in two stages: The primary vaccination phase (Study Stage 1) of the study will include all subjects; the second (booster/persistence) phase of the study (Study Stage 2) will include subjects in the active control groups and in the group which was primed with the selected MenACWY formulation.

The study will be conducted in a double-blind manner for groups receiving formulations A, B, C and in single blind manner with respect to the group receiving formulation D. The control vaccines will be administered in an open manner with respect to the investigational vaccination regimens.

Each group will have one blood sample prior to and one blood sample one month after the first vaccine dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 461
• Est. completion date: March 3, 2006
• Est. primary completion date: March 1, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 60 Months

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 12 and 14 months or 3 and 5 years of age at the time of the first vaccination.

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

• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

• Previously completed routine childhood vaccinations to the best of his/her parents'/guardians' knowledge. For pertussis vaccination, the children aged 12-14 months should have been vaccinated with an acellular pertussis vaccine.

Exclusion criteria:

• 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) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the first dose of vaccine and up to one month after administration of each study vaccine dose with the exception of oral polio vaccine (OPV).

• Previous vaccination against meningococcal serogroup A, C, W-135 or Y disease.

• Administration of a H. influenzae type b, diphtheria or tetanus vaccine within 3 months before the first dose of vaccine.

• For subjects aged 12-14 months at enrolment:

• For Austria: DTPa-HBV-IPV/Hib booster vaccination in the second year of life:

these booster vaccines will be given at Visit 2.

• For Greece: DTPa-IPV/Hib booster vaccination in the second year of life: these booster vaccines will be given at Visit 2.

• History of meningococcal serogroup A, C, W-135 or Y disease.

• Known exposure to meningococcal serogroup A, C, W-135 or Y disease within the previous year.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.

• A family history of congenital or hereditary immunodeficiency.

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

• Major congenital defects or serious chronic illness.

• History of any neurologic disorders or seizures.

• Acute disease at the time of enrolment.

• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

Related Conditions & MeSH terms

• Infections, Meningococcal
• Meningococcal Infections

Intervention

Biological:
• Conjugated meningococcal ACWY-TT (vaccine)
One intramuscular dose during the primary vaccination
• DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
One intramuscular dose during the primary vaccination study in subjects of 12-24 months of age, in Greece only
• DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
One intramuscular dose during the primary vaccination study in subjects of 12-24 months of age, in Austria only
• Meningitec™
One intramuscular dose during the primary vaccination study in subjects of 12-24 months of age
• Mencevax™ACWY
One subcutaneous dose during the primary vaccination study in subjects of 3-5 years of age (Group E) and intramuscular administration of 1/5 dose during the booster vaccination study in subjects of 12-14 months of age (Groups A and E)

Locations

Country	Name	City	State
Austria	GSK Investigational Site	Eferding
Austria	GSK Investigational Site	Graz
Austria	GSK Investigational Site	Salzburg
Austria	GSK Investigational Site	Vienna
Austria	GSK Investigational Site	Villach
Austria	GSK Investigational Site	Wels
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion, Crete
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Komotini
Greece	GSK Investigational Site	Koufalia
Greece	GSK Investigational Site	Markopoulo
Greece	GSK Investigational Site	N. Efkarpia, Thessaloniki
Greece	GSK Investigational Site	Nea Makri
Greece	GSK Investigational Site	Rio/Patras
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Tripolis

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Austria,  Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With an Immune Response to Different Meningococcal Serogroups	A responder to serum bactericidal assay meningococcal serogroups A, C, W and Y, using rabbit complement (rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY) was defined as follows: -for initially seronegative subjects (antibody titers < 1:8 for rSBA-Men), a subject achieving a post-vaccination rSBA-Men antibody titer of = 1:32; - for initially seropositive subjects (antibody titers = 1:8 for rSBA-Men), a subject having a = 4-fold increase in rSBA-Men antibody titer from pre to post vaccination.	One month after the first vaccine dose (Month 1)
Secondary	Number of Seroprotected Subjects Against Different Meningococcal Serogroups	A seroprotected subject against meningococcal serogroups rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY assessed, was defined as having antibody titers greater than or equal to (=) 1:8.	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Number of Seropositive Subjects for Different Anti-meningococcal Serogroups	A seropositive subject for meningococcal serogroups rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-Y assessed, was defined as having antibody titers greater than or equal to (=) 1:128.	Prior to (Month 0) and one month after (Month 1) after the first vaccine dose
Secondary	Antibody Titers Against Different Meningococcal Serogroups	Antibody titers against meningococcal serogroups A, C, W-135 and Y (MenA, MenC, MenW-135 and MenY) have been assessed, using rabbit complement and expressed as geometric mean titers (GMTs).	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Number of Seropositive Subjects for Different Anti-meningococcal Polysaccharides	A seropositive subject for meningococcal polysaccharide A (PSA), C (PSC), W-135 (PSW-135) and Y (PSY) assessed, was defined as having antibody (anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY) concentrations greater than or equal to (=) the cut-off value of 0.3 micrograms per milliliter (µg/mL). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA).	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Number of Seroprotected Subjects Against Different Meningococcal Polysaccharides	A seroprotected subject for meningococcal polysaccharide A (PSA), C (PSC), W-135 (PSW-135) and Y (PSY) assessed, was defined as having antibody (anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY) concentrations greater than or equal to (=) the value of 2.0 micrograms per milliliter (µg/mL). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA).	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Antibody Concentrations Against Different Meningococcal Polysaccharides	The meningococcal polysaccharides assessed included polysaccharide A (anti-PSA), polysaccharide B (anti-PSB), polysaccharide W-135 (anti-PSW-135) and polysaccharide Y (anti-PSY). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Number of Seropositive Subjects for Anti-tetanus (Anti-T)	A seropositive subject for anti-tetanus was defined as having antibody concentrations greater than or equal to (=) the cut-off value of 0.1 international units per milliliter (IU/mL). Antibody titers were determined by enzyme-linked immunosorbent assay (ELISA).	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Antibody Concentrations Against Tetanus (Anti-T)	Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) method, presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL).	Prior to (Month 0) and one month after (Month 1) the first vaccine dose
Secondary	Number of Toddlers With Any Solicited Local Symptoms	The toddlers subgroup received 2 primary vaccine doses, as follows: first dose of a meningococcal vaccine and second dose of a diphtheria, tetanus and acellular pertusis-containing vaccine. Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.	During the 8-day (Days 0-7) post-vaccination period after each primary vaccine dose
Secondary	Number of Children With Any Solicited Local Symptoms	The children subgroup received one dose of the meningococcal vaccine. Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.	During the 8-day (Days 0-7) post-vaccination period after each primary vaccine dose
Secondary	Number of Toddlers With Any Solicited General Symptoms	The toddlers subgroup received 2 primary vaccine doses, as follows: first dose of a meningococcal vaccine and second dose of a diphtheria, tetanus and acellular pertusis-containing vaccine. Assessed solicited general symptoms included drowsiness, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = incidence of a particular symptom regardless of intensity or relationship to vaccination.	During the 8-day (Days 0-7) post-vaccination period after each primary vaccine dose
Secondary	Number of Children With Any Solicited General Symptoms	The children subgroup received one primary meningococcal vaccine dose. Assessed solicited general symptoms included drowsiness, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = incidence of a particular symptom regardless of intensity or relationship to vaccination.	During the 8-day (Days 0-7) post-vaccination period after each primary vaccine dose
Secondary	Number of Seroprotected Subjects Against Different Meningococcal Serogroups	A seroprotected subject against meningococcal serogroups rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY assessed, was defined as having antibody titers greater than or equal to (=) 1:8.	At one month (M1) and 12 months (M12) post-primary vaccination
Secondary	Number of Seropositive Subjects for Different Anti-meningococcal Serogroups	A seropositive subject for meningococcal serogroups rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-Y assessed, was defined as having antibody titers greater than or equal to (=) 1:128.	At one month (M1) and 12 months (M12) post-primary vaccination
Secondary	Antibody Titers Against Different Meningococcal Serogroups	Antibody titers against meningococcal serogroups A, C, W-135 and Y (MenA, MenC, MenW-135 and MenY) have been assessed, using rabbit complement and expressed as geometric mean titers (GMTs).	At one month (M1) and 12 months (M12) post-primary vaccination
Secondary	Number of Seropositive Subjects for Different Anti-meningococcal Polysaccharides	A seropositive subject for meningococcal polysaccharide A (PSA), C (PSC), W-135 (PSW-135) and Y (PSY) assessed, was defined as having antibody (anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY) concentrations greater than or equal to (=) the cut-off value of 0.3 micrograms per milliliter (µg/mL). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA).	At one month (M1) and 12 months (M12) post-primary vaccination
Secondary	Number of Seroprotected Subjects Against Different Meningococcal Polysaccharides	A seroprotected subject for meningococcal polysaccharide A (PSA), C (PSC), W-135 (PSW-135) and Y (PSY) assessed, was defined as having antibody (anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY) concentrations greater than or equal to (=) the value of 2.0 micrograms per milliliter (µg/mL). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA).	At one month (M1) and 12 months (M12) post primary vaccination
Secondary	Antibody Concentrations Against Different Meningococcal Polysaccharides	The meningococcal polysaccharides assessed included polysaccharide A (anti-PSA), polysaccharide B (anti-PSB), polysaccharide W-135 (anti-PSW-135) and polysaccharide Y (anti-PSY). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).	At one month (M1) and 12 months (M12) post-primary vaccination
Secondary	Number of Seropositive and Seroprotected Subjects Against Different Meningococcal Serogroups	A seropositive subject for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY was defined as a vaccinated subject with antibody titers greater than or equal to (=) 1:128, while for a seroprotected subject, titers were =1:8.	Before (PRE= at Month 12) and one month after (at Month 13) booster vaccination
Secondary	Antibody Titers Against Different Meningococcal Serogroups	Antibody titers against meningococcal serogroups A, C, W-135 and Y (MenA, MenC, MenW-135 and MenY) have been assessed, using rabbit complement and expressed as geometric mean titers (GMTs).	Before (PRE= at Month 12) and one month after (at Month 13) booster vaccination
Secondary	Number of Seropositive and Seroprotected Subjects Against Different Meningococcal Polysaccharides	A seropositive subject for anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY was defined as a vaccinated subject with antibody concentrations greater than or equal to (=) 0.3 micrograms per milliliter (µg/mL), while for a seroprotected subject, antibody concentrations were = 2.0 µg/mL.	Before (PRE= at Month 12) and one month after (at Month 13) booster vaccination
Secondary	Antibody Concentrations Against Different Meningococcal Polysaccharides	The meningococcal polysaccharides assessed included polysaccharide A (anti-PSA), polysaccharide B (anti-PSB), polysaccharide W-135 (anti-PSW-135) and polysaccharide Y (anti-PSY). Antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL).	Before (PRE= at Month 12) and one month after (at Month 13) booster vaccination
Secondary	Number of Subjects With Any Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.	During the 8-day (Days 0-7) post-vaccination period following booster dose
Secondary	Number of Subjects With Any Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, fever [defined as rectal temperature equal to or above 38.0 degrees Celsius (°C)], irritability and loss of appetite. Any = incidence of a particular symptom regardless of intensity or relationship to vaccination.	During the 8-day (Days 0-7) post-vaccination period following booster dose
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs) After the Primary Vaccination	An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	Within 31 days (Days 0-30) after the primary meningococcal vaccination
Secondary	Number of Subjects With Any Unsolicited AEs During the Primary Vaccination	An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	Within 31 days (Days 0-30) post-vaccination with diphteria, tetanus and acellular pertusis-containing vaccine, during the primary vaccination
Secondary	Number of Subjects With Any Unsolicited AEs	An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	Within 31 days (Days 0-30) after the booster vaccination
Secondary	Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the primary vaccination study (from Month 0 up to Month 2)
Secondary	Number of Subjects With SAEs	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	Since the last study contact in the primary study up to the end of the booster study (from Month 2 up to Month 13)

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