Clinical trial NCT03621670: Safety and Immunogenicity of GSK Meningococcal Group B Vaccine and 13-valent Pneumococcal Vaccine Administered Concomitantly With Routine Infant Vaccines to Healthy Infants
Official title: Safety and Immunogenicity of GSK Meningococcal Group B Vaccine and 13-valent Pneumococcal Vaccine Administered Concomitantly With Routine Infant Vaccines to Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Meningococcal
Keywords: Meningitis
Immune response
Sufficiency
Neisseria meningitides
Bexsero
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2018-08-08
Enrollment: 1196
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety and immunogenicity of Bexsero (meningococcal group B vaccine-rMenB+OMV NZ) in North American infants 6 weeks through 12 weeks of age, when administered concomitantly with Pneumococcal conjugate vaccine (PCV 13) and other recommended routine infant vaccines(RIV).

Detailed description: This study will be divided into 3 timepoints:

* Epoch 1- Primary- From Day 1 to Day 301
* Epoch 2-Secondary-From Day 301 to Day 331
* Epoch 3-Safety follow up -From Day 331 to study end (Day 481 or Day 661). For subjects who have not yet reached the 6-month safety follow-up after the last dose at the time protocol amendment 7 takes effect, Visit 7 will take place on Day 481.

In addition to receiving the study vaccines, infants will also receive non-study vaccines such as Diphtheria, tetanus toxoids and acellular pertussis adsorbed vaccine (DTPa, Infanrix) and Haemophilus influenzae type b Conjugate Vaccine (Hib, Hiberix), to ease the disruption to the standard infant vaccine schedule caused by participating in this study.

Eligibility criteria: Inclusion Criteria:

All subjects must satisfy all the following criteria at study entry:

* Subjects' parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the eDiary, return for follow-up visits).
* Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
* A male or female between, and including, 42 and 84 days of age (i.e., 6 through 12 weeks) at the time of the 1st vaccination.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Born full-term (i.e. after a gestation period of ≥ 38 weeks).

Exclusion Criteria:

If any exclusion criterion applies, the subject must not be included in the study:

• Child in care

Each subject must not have:

* Progressive, unstable or uncontrolled clinical conditions.
* Hypersensitivity, including allergy to any component of vaccines, medicinal product or medical equipment whose use is foreseen in this study.
* Hypersensitivity to latex.
* Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
* Abnormal function of the immune system resulting from:

  * Clinical conditions.
  * Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days from birth.
  * Administration of antineoplastic and immunomodulating agents or radiotherapy for any duration from birth.
  * Autoimmune disorders (including, but not limited to: blood, endocrine, hepatic, muscular, nervous system or skin autoimmune disorders; lupus erythematosus and associated conditions; rheumatoid arthritis and associated conditions; scleroderma and associated disorders) or immunodeficiency syndromes (including, but not limited to: acquired immunodeficiency syndromes and primary immunodeficiency syndromes).
* Received immunoglobulins or any blood products from birth.
* Received an investigational or non-registered medicinal product from birth.
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
* Neuroinflammatory disorders (including but not limited to: demyelinating disorders, encephalitis or myelitis of any origin), congenital and peripartum neurological conditions, encephalopathies, seizures (including all subtypes such as: absence seizures, generalised tonic-clonic seizures, partial complex seizures, partial simple seizures or febrile convulsions).
* Congenital or peripartum disorders resulting in a chronic condition (including but not limited to: chromosomal abnormalities, cerebral palsy, metabolism or synthesis disorders, cardiac disorders).
* Study personnel as an immediate family or household member.
* Current or previous, confirmed or suspected disease caused by N. meningitidis
* Household contact with and/or intimate exposure from birth to an individual with laboratory confirmed N. meningitidis and/or Streptococcus pneumoniae infection or colonization.
* Previous administration of meningococcal B or pneumococcal vaccine at any time prior to informed consent.
* Received a dose of DTPa-HBV-IPV, HRV, MMR, VV and/or Hib at any time prior to informed consent. Receipt of one dose of HBV up to 4 weeks prior to informed con-sent is allowed.
* Serious chronic illness.
* Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS).

Primary outcomes:
measure: Percentages of subjects with solicited local (administration site event) and systemic Adverse Events (AEs)
timeFrame: During the 7-day follow-up period after the 1st vaccination
measure: Percentages of subjects with solicited local (administration site event) and systemic AEs
timeFrame: During the 7-day follow-up period after the 2nd vaccination
measure: Percentages of subjects with solicited local (administration site event) and systemic AEs
timeFrame: During the 7-day follow-up period after the 3rd vaccination
measure: Percentages of subjects with solicited local (administration site event) and systemic AEs
timeFrame: During the 7-day follow-up period after the 4th vaccination
measure: Percentages of subjects with solicited systemic AEs
timeFrame: During the 30-day (Day 1 - Day 30) follow-up period after the 4th vaccination
measure: Percentages of subjects with all unsolicited AEs
timeFrame: During the 30-day follow-up period after the 1st vaccination
measure: Percentages of subjects with all unsolicited AEs
timeFrame: During the 30-day follow-up period after the 2nd vaccination
measure: Percentages of subjects with all unsolicited AEs
timeFrame: During the 30-day follow-up period after the 3rd vaccination
measure: Percentages of subjects with all unsolicited AEs
timeFrame: During the 30-day follow-up period after the 4th vaccination
measure: Percentages of subjects with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs
timeFrame: Throughout the study period [Day 1 up to study end (Day 481 or Day 661)]
measure: Percentages of subjects with human serum bactericidal assay (hSBA) antibody titers ≥ Lower Limit of Quantitation (LLOQ) for each of the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with hSBA antibody titers ≥LLOQ for all strains combined (M14459, 96217, NZ98/254 and M13520)
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) for each of the test strains
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: Percentages of subjects with hSBA titers ≥ 8 (for strains M14459, NZ98/254, M13520) and ≥16 (for strain 96217) for all strains combined (composite endpoint)
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: Antibody Geometric Mean Concentrations (GMC) using electrochemiluminescence (ECL) assay for each of the 13 PCV13 antigens
timeFrame: At 1 month after the 3rd vaccination (Day 151)
Secondary outcomes:
measure: Antibody GMCs using ECL for each of the 13 PCV13 serotypes
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: Percentages of subjects with serum pneumococcal anti-capsular polysaccharide IgG ≥0.35 μg/mL
timeFrame: At one month after the 3rd vaccination (Day 151) and one month after 4th vaccination (Day 331)
measure: GMCs against 3 pertussis antigens (pertussis toxin [PT], pertactin [PRN], filamentous hemagglutinin [FHA])
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with antibodies concentrations against hepatitis B surface antigen (AntiHBsAg) ≥10 mIU/mL
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥0.1 IU/mL
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with anti-polyribosyl-ribitol phosphate (PRP) concentration ≥0.15 µg/mL and ≥1 µg/mL
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: GMCs for anti-Varicella (VV) antibodies
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: GMCs for anti-measles antibodies
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: GMCs for anti-mumps antibodies
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: GMCs for anti-rubella antibodies
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: Percentages of subjects with hSBA antibody titers ≥5 and ≥8 and ≥16 for each of the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with hSBA antibody titers ≥5 and ≥8 for each of the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 6 months after the 3rd vaccination (Day 301)
measure: Percentages of subjects with hSBA antibody titers ≥5 for each of the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: hSBA Geometric Mean Titers for the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 1 month after the 3rd vaccination (Day 151) and 6 months after 3rd vaccination (Day 301) and 1 month after 4th vaccination (Day 331)
measure: Percentages of subjects with hSBA antibody titers ≥LLOQ for each of the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 6 months after the 3rd vaccination (Day 301) and 1 month after 4th vaccination (Day 331)
measure: hSBA Geometric Mean Ratios (GMR) of GMTs over pre 4th vaccination for the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 1 month after the 4th vaccination (Day 331) versus pre-4th vaccination (Day 301)
measure: Percentages of subjects with 4-fold rise in hSBA titers (from pre-4th vaccination) for each of the M14459, 96217, NZ98/254 and M13520 test strains
timeFrame: At 1 month after the 4th vaccination (Day 331)
measure: Percentages of subjects with anti-HBs antibody concentrations ≥100 mIU/mL
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: GMCs for Anti-HBsAg antibodies
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥1 IU/mL
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: GMCs for anti-diphtheria and anti-tetanus antibodies
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects with anti-polio type 1, 2 and 3 neutralization antibody titers ≥8
timeFrame: At 1 month after the 3rd vaccination (Day 151)
measure: Percentages of subjects showing seroresponse for anti-Varicella (VV), anti-measles virus, anti-mumps virus and anti-rubella virus antibodies
timeFrame: At 1 month after the 4th vaccination (Day 331)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Fayetteville
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facility: GSK Investigational Site
state: Arkansas
city: Jonesboro
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facility: GSK Investigational Site
state: Arkansas
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city: Baltimore
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city: Fall River
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city: Bingham Farms
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state: Michigan
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city: Liverpool
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state: New York
city: Syracuse
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state: New York
city: Boone
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Fairfield
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facility: GSK Investigational Site
state: Ohio
city: South Euclid
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state: Ohio
city: Hermitage
country: United States
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state: Pennsylvania
city: Pittsburgh
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facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
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facility: GSK Investigational Site
state: South Carolina
city: Charleston
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state: South Carolina
city: Sioux Falls
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facility: GSK Investigational Site
state: South Dakota
city: Clarksville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Beaumont
country: United States
facility: GSK Investigational Site
state: Texas
city: Bryan
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
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state: Texas
city: San Antonio
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state: Texas
city: Layton
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state: Utah
city: Orem
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state: Utah
city: Provo
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state: Utah
city: Salt Lake City
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state: Utah
city: Syracuse
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city: Richmond
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state: Virginia
city: Tacoma
country: United States
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state: Washington
city: Marshfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Edinburg
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: