Can we Reduce the Number of Vaccine Injections for Children?

Study Overview
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Brief Summary
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This open label randomised controlled study will evaluate the induction of immunity following varying schedules of vaccination with glyco-conjugate Neisseria meningitidis serogroup C (MenC) vaccines in infancy. 498 infants will be enrolled in this multi-centre trial. Participants will receive either 0, 1, or 2 priming doses of a MenC-CRM197 conjugate vaccine or 1 priming dose of a MenC-TT conjugate vaccine in the first year of life, with all groups receiving a dose of a combination Hib-MenC-TT vaccine at 12 months, as well as all other concurrent routine vaccinations. All groups will also be further divided into 2 groups to receive their routine vaccines in either consistent or alternating limbs to assess the immune response to the concurrent infant routine immunisations administered in consistent versus alternating limbs. Immune responses will be assessed at 5, 12, 12months +6 days, 13 and 24 months of age.

Official Title
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An Open Label Randomised Controlled Study to Evaluate the Induction of Immune Memory Following Infant Vaccination With a Glycoconjugate Neisseria Meningitidis Serogroup C Vaccine and to Assess the Immunological Impact of Administering Routine Infant Immunisations in Consistent Versus Alternating Limbs

Conditions
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Invasive Meningococcal Disease

Intervention / Treatment
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* Biological: Glyco-conjugate Neisseria meningitidis serogroup C (MenC) vaccine
* Biological: Routine schedule immunisations except monovalent MenC vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female infants aged 6-12 weeks at the time of the first vaccination and who were born between 37 and 42 weeks of gestation Infants who are known to be free from medical problems as determined by a medical history and clinical examination Parents or guardians who are willing for their child to participate and who would be expected to comply with the requirements of the protocol Parents/guardians who have given informed consent for their child's participation in the study Exclusion Criteria: History of invasive meningococcal C disease Previous vaccination against meningococcal serogroup C disease Planned administration/administration of vaccines, since birth, other than the study vaccines (with the exception of oral rotavirus vaccine, Hepatitis B vaccine and BCG). Receipt of investigational vaccines/drugs, other than the vaccines used in the study, within 30 days prior to receiving the first dose of the vaccines or their planned use during the study period Confirmed or suspected immunosuppressive or immunodeficient conditions, including human immunodeficiency virus (HIV) infection. A family history of congenital or hereditary immunodeficiency. Receipt of more than 2 weeks of immunosuppressants or immune modifying drugs, (e.g. prednisolone >0.5mg/kg/day) History of allergy to any component of the vaccines. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures Acute disease at the time of recruitment as defined by the presence of a moderate or severe illness with or without fever (with the exception of minor illnesses such as diarrhoea, mild upper respiratory infection without fever). In such situations enrolment should be postponed until the participant has recovered. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period Parents who plan to move out of the geographical area where the study would be conducted.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Two Dose MenC Group<br>Two doses of MenC-CRM197 priming at 3 and 4 months of age. | Biological: Glyco-conjugate Neisseria meningitidis serogroup C (MenC) vaccine<br>* In order to ensure proper intramuscular injection of the study vaccines, a 23G (0.5mm in diameter) needle of at least 1 inch (2.54 cm) length will be used. All vaccines will be administered intramuscularly. Then MenC vaccine will administered either once (at 3 months) or twice (at 3 and 4 months) depending on treatment group to either the thigh, deltoid or a combination of the two.<br>Biological: Routine schedule immunisations except monovalent MenC vaccine<br>* Routine schedule immunisations will be given according to NHS guidelines.<br>|
| Experimental: Single Dose MenC-CRM197 Group<br>One dose of MenC-CRM197 priming at 3 months of age. | Biological: Glyco-conjugate Neisseria meningitidis serogroup C (MenC) vaccine<br>* In order to ensure proper intramuscular injection of the study vaccines, a 23G (0.5mm in diameter) needle of at least 1 inch (2.54 cm) length will be used. All vaccines will be administered intramuscularly. Then MenC vaccine will administered either once (at 3 months) or twice (at 3 and 4 months) depending on treatment group to either the thigh, deltoid or a combination of the two.<br>Biological: Routine schedule immunisations except monovalent MenC vaccine<br>* Routine schedule immunisations will be given according to NHS guidelines.<br>|
| Experimental: Single Dose MenC-TT Group<br>Single dose MenC-TT priming at 3 months of age | Biological: Glyco-conjugate Neisseria meningitidis serogroup C (MenC) vaccine<br>* In order to ensure proper intramuscular injection of the study vaccines, a 23G (0.5mm in diameter) needle of at least 1 inch (2.54 cm) length will be used. All vaccines will be administered intramuscularly. Then MenC vaccine will administered either once (at 3 months) or twice (at 3 and 4 months) depending on treatment group to either the thigh, deltoid or a combination of the two.<br>Biological: Routine schedule immunisations except monovalent MenC vaccine<br>* Routine schedule immunisations will be given according to NHS guidelines.<br>|
| Experimental: Control Group<br>Zero dose MenC priming | Biological: Routine schedule immunisations except monovalent MenC vaccine<br>* Routine schedule immunisations will be given according to NHS guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titres (GMTs) of meningococcal serogroup C (MenC) specific serum bactericidal antibodies, using rabbit complement (rSBA) | To demonstrate non-inferiority of the geometric mean titres (GMTs) of meningococcal serogroup C (MenC) specific serum bactericidal antibodies, using rabbit complement (rSBA), 1 month after a 12 month dose of Hib-MenC vaccine in children receiving a single dose of MenC-CRM197vaccine at 3 months of age (single dose priming) compared with those receiving 2 doses at 3 and 4 months of age (2 dose priming). | 1 month after a 12 month dose of Hib-MenC vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meningococcal serogroup C, vaccine, conjugate