Safety and Immunogenicity Evaluation After One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants and Toddlers

Study Overview
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Brief Summary
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The primary immunogenicity objective is to assess and compare the immunogenicity of one dose of MenACWY to one dose of Menjugate given to healthy toddlers at 12 months of age as measured by the percentage of subjects with serum bactericidal titers directed against N. meningitidis serogroup C ≥ 1:8 obtained in the serum bactericidal assay using human complement (hSBA).

Official Title
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A Phase 3, Open-Label, Randomized, Multi-Center Study to Evaluate the Safety and Immunogenicity After One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine Administered to Healthy Infants and Toddlers

Conditions
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Meningococcal Meningitis

Intervention / Treatment
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* Biological: MenACWY-CRM197 (two doses)
* Biological: MenC
* Biological: PCV7
* Biological: DTPa-IPV-HepB-Hib
* Biological: MenACWY-CRM197 (one dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants 6 to 8 months old inclusive, who were born after full term pregnancy and previously received three doses of both Prevenar and Infanrix-hexa vaccines at least 30 days before study entry Exclusion Criteria: who previously received any meningococcal vaccine; who have had a previous confirmed or suspected disease caused by N. meningitidis, C. diphtheriae, C. tetani, Poliovirus, Hepatitis B, Hib, Pneumococcus or B. pertussis; who have had household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis (serogroups A, C, W135, or Y), B. pertussis, Hib, C. diphtheriae, Polio, or pneumococcal infection at any time since birth; Subjects with any serious, acute or chronic progressive disease

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 8 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: MenACWY-CRM197 (2 doses) + Concomitant Vaccines<br>Infants received two doses of MenACWY-CRM197 at 6 to 8 and 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months. | Biological: MenACWY-CRM197 (two doses)<br>* Two 0.5mL doses of MenACWY conjugate vaccine (MenACWY-CRM197) was administered by intramuscular injection.<br>Biological: PCV7<br>* One 0.5mL dose of Pneumococcal 7-valent Conjugate Vaccine (PCV7) was administered by intramuscular injection.<br>Biological: DTPa-IPV-HepB-Hib<br>* One 0.5mL dose of Combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b (DTPa-IPV-HepB-Hib) vaccine was administered by intramuscular injection.<br>|
| Experimental: MenACWY-CRM197 (1 dose) + Concomitant Vaccines<br>Infants received one dose of MenACWY-CRM197 at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age. | Biological: PCV7<br>* One 0.5mL dose of Pneumococcal 7-valent Conjugate Vaccine (PCV7) was administered by intramuscular injection.<br>Biological: DTPa-IPV-HepB-Hib<br>* One 0.5mL dose of Combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b (DTPa-IPV-HepB-Hib) vaccine was administered by intramuscular injection.<br>Biological: MenACWY-CRM197 (one dose)<br>* One 0.5mL dose of MenACWY conjugate vaccine (MenACWY-CRM197) was administered by intramuscular injection.<br>|
| Active Comparator: MenC (1 dose) + Concomitant Vaccines<br>Infants received one dose of MenC vaccine at 12 months of age and concomitant dose of PCV7 (Pneumococcal 7-valent Conjugate Vaccine) and DTPa-IPV-HepB-Hib (Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b) at 12 months of age. | Biological: MenC<br>* One 0.5mL dose of MenC vaccine was administered by intramuscular injection.<br>Biological: PCV7<br>* One 0.5mL dose of Pneumococcal 7-valent Conjugate Vaccine (PCV7) was administered by intramuscular injection.<br>Biological: DTPa-IPV-HepB-Hib<br>* One 0.5mL dose of Combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type b (DTPa-IPV-HepB-Hib) vaccine was administered by intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Serum Bactericidal Titer ≥ 1:8 Against N.Meningitidis Serogroup C | Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was measured using serum bactericidal assay with human complement (hSBA) titer ≥ 1:8 against N.meningitidis serogroup C. | 1 month postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:4 Against N.Meningitidis Serogroup C | Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentage of subjects with serum bactericidal activity using human complement (hSBA) titers ≥ 1:4 against N. meningitidis serogroup C. | 1 month postvaccination | 
| Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, C, W, Y | Immunogenicity of two doses of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month postvaccination was assessed and compared as percentages of subjects with serum bactericidal titer with human complement (hSBA) ≥ 1:8, ≥ 1:4 against N.meningitidis Serogroup C. Immunogenicity of two doses of MenACWY-CRM197 vaccine one month postvaccination was assessed as percentages of subjects with serum bactericidal titer with human complement (hSBA) ≥ 1:8, ≥ 1:4 against N.meningitidis Serogroup A, W, Y. | 1 month postvaccination. | 
| Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, W, Y | Immunogenicity for one dose of MenACWY was assessed as percentages of subjects with serum bactericidal titer with human complement (hSBA) ≥ 1:8 and titer ≥ 1:4 by serogroups A, W, Y. Serogroup C is not shown here as it is shown in other outcome measures. | 1 month postvaccination. | 
| Human Serum Bactericidal Activity Geometric Mean Titers After One Dose of MenACWY-CRM197 and MenC Against N.Meningitidis Serogroup C | Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed with geometric mean titer (GMT) of serum bactericidal assay with human complement (hSBA) against N. meningitidis serogroup C. | 1 month postvaccination | 
| Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y | Immunogenicity of one dose of MenACWY-CRM197 one month postvaccination was assessed with GMT of serum bactericidal assay with hSBA against Serogroups A, W, Y. | 1 month postvaccination | 
| Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, C, W, Y | The immunogenicity of two doses of MenACWY-CRM197, to a single dose of MenC was assessed and compared as measured by human Serum Bactericidal Activity Geometric Mean Titers directed against N. meningitidis serogroup C. The immunogenicity of two doses of MenACWY-CRM197, to a single dose of MenC was assessed as measured by human Serum Bactericidal Activity Geometric Mean Titers directed against N. meningitidis serogroups A, W, Y. | 1 month postvaccination | 
| Percentages of Subjects With Seroresponse Rates After One Dose of DTPa-IPV-HepB-Hib (Concomitant Vaccine) | The immunogenicity of one dose of MenC to one dose of DTPa-IPV-HepB-Hib concomitant vacccine was assessed. For Pertussis antigens, Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN), the seroresponse in initially seronegative subjects (pre-vaccination antibody concentration < LLQ) is defined as post-vaccination antibody concentration >= LLQ; in initially seropositive subjects (pre-vaccination antibody concentration >=LLQ) seroresponse is defined as at least two fold increase of the pre-vaccination antibody concentration. Diptheria and Tetanus: primary endpoint ELISA (Enzyme-linked immunosorbent assay) >=0.1 (international unit -IU) IU/mL and the secondary endpoint is ELISA>=1.0 IU/mL. Polio type 1, 2 and 3: bNT (neutralization test) with >=1:8. HepB (HBV): primary endpoint ELISA >=10mU/mL. PRP-T: primary endpoint ≥ 0.15 mcg/mL and ≥ 1.00 mcg/mL. | 1 month postvaccination | 
| Percentages of Subjects With Seroresponse Rates After One Dose of PCV7 (Concomitant Vaccine) | To compare the immunogenicity of PCV7 (Pneumococcal 7-valent Conjugate)Vaccine when given concomitantly with one dose or two doses of MenACWY-CRM197 or with MenC to infants at 12 months of age. Seroresponse for PCV7 (PnC 4, PnC 6B, PnC 9V, PnC 14, PnC 18C, PnC 19F, PnC 23F) is defined as: a subject with primary endpoint ELISA ≥ 0.35 mcg/mL and secondary endpoint ELISA ≥ 1.0 mcg/mL. | 1 month postvaccination | 
| Persistence of Immune Response Measured as Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 and Titer ≥ 1:4 Against N. Meningitidis Serogroup C | Persistence of immune response to either one or two doses of MenACWY-CRM197 or one dose of MenC as measured by serum bactericidal assay with human complement (hSBA) titers ≥ 1:8, and titers ≥ 1:4 directed against N.meningitidis serogroup C (only for subjects enrolled in Australia). | 1 month postvaccination and 6-18 months postvaccination. | 
| Persistence of Immune Response Measured as Percentages of Subjects With Human Serum Bactericidal Titer ≥ 1:8 ,and Titer ≥ 1:4 Against N. Meningitidis Serogroups A, W, Y | Persistence of immune response to either one or two doses of MenACWY-CRM197 or one dose of MenC as measured by serum bactericidal assay with human complement (hSBA) titer ≥ 1:8 and titer ≥ 1:4 directed against N. meningitidis serogroups A, W and Y (only for subjects enrolled in Australia). | 1 month postvaccination 6-18 months postvaccination | 
| Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C | Persistence of immunogenicity of either one or two doses of MenACWY or one dose of MenC as measured by human serum bactericidal activity geometric mean titers directed against N.meningitidis serogroup C (only for subjects enrolled in Australia). | 1 month postvaccination and 6-18 months postvaccination. | 
| Persistence of Human Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroups A, W, Y | Immunogenicity of two doses of MenACWY to one dose of MenACWY as measured by hSBA GMTs directed against N.meningitidis serogroups A, W, Y (only for subjects enrolled in Australia). | 6-18 months postvaccination. | 
| Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128 and Four Fold Rise Against N.Meningitidis Serogroup C | Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup C. Immunogenicity of two doses of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup C. | 1 month postvaccination. | 
| Percentages of Subjects With Rabbit Serum Bactericidal ≥ 1:8, ≥ 1:128, and Four Fold Rise Against N.Meningitidis Serogroup A, W, Y | Immunogenicity of one dose of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup A, W, Y. Immunogenicity of two doses of MenACWY-CRM197 vaccine to one dose of MenC vaccine one month post vaccination was assessed as percentages of subjects with serum bactericidal titer with rabbit complement (rSBA) ≥ 1:8, ≥ 1:128, and four fold rise in titer against N.meningitidis Serogroup A, W, Y. | 1 month postvaccination. | 
| Rabbit Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup C | Immunogenicity of one dose of MenACWY-CRM197 to one dose of MenC vaccine at 12 months of age was assessed with geometric mean titer (GMT) of serum bactericidal assay with rabbit complement (rSBA) against Serogroup C. Immunogenicity of two doses of MenACWY-CRM197 to one dose of MenC vaccine at 6 to 8 and 12 months of age was assessed with geometric mean titer (GMT) of serum bactericidal assay with rabbit complement (rSBA) against Serogroup C. | 1 month postvaccination. | 
| Rabbit Serum Bactericidal Activity Geometric Mean Titers Against N.Meningitidis Serogroup A, W, Y | Immunogenicity of one dose of MenACWY-CRM197 to one dose of MenC vaccine at 12 months of age was assessed with GMT of SBA with rabbit complement (rSBA) against Serogroup A, W, Y. Immunogenicity of two doses of MenACWY-CRM197 to one dose of MenC vaccine at 6 to 8 and 12 months of age was assessed with geometric mean titer (GMT) of serum bactericidal assay with rabbit complement (rSBA) against Serogroup A, W, Y. | 1 month postvaccination. | 
| Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 to Day 7 Postvaccination), After Any Vaccination | Safety was assessed as the number of subjects who reported solicited local reactions from day 1 to day 7 postvaccination for all the three vaccination groups. safety was assessed as the number of subjects who reported solicited systemic reactions from day 1 to day 7 Following the Month 12 vaccination in all three vaccination groups | From day 1 to day 7 postvaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal, ACWY, Conjugate Vaccine, Meningitis, Toddlers, Infants, Concomitant Vaccination