A Study to Evaluate the Safety and Immunogenicity of 4 Doses of MenACWY Conjugate Vaccine, Administered Concomitantly With Routine Vaccines, Among Infants Aged 2 Months

Study Overview
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Brief Summary
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This Phase 3 study is designed to demonstrate the safety and immunogenicity of MenACWY and non-interference of concomitant routine vaccines by MenACWY in an infant age group.

Official Title
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A Phase 3, Randomized, Open Label, Controlled Multicenter Study to Evaluate the Safety and Immunogenicity of 4 Doses of MenACWY Conjugate Vaccine, Administered Concomitantly With Routine Vaccines, Among Infants Aged 2 Months

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: MenACWY-CRM
* Biological: DTaP-IPV/Hib
* Biological: HBV
* Biological: PCV
* Biological: MMR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Two month-old infants, born after a full-term pregnancy with an estimated gestational age ≥37 weeks and a birth weight ≥2.5 kg. Documented written informed consent provided by the parent/legal representative after the nature of the study had been explained. Parent/legal representative was available for all visits scheduled in the study. Subjects were in good health as determined by: medical history physical assessment clinical judgment of the investigator Exclusion Criteria: Subjects who previously received any meningococcal vaccines or vaccines against diphtheria, tetanus, pertussis, polio (IPV or OPV), H. influenzae type b (Hib) or pneumococcus. Exceptions: prior doses HBV vaccination (one or two doses) are permitted. Subjects who had a previous confirmed or suspected disease caused by N. meningitidis, C. diphtheriae, C. tetani, poliovirus, Hepatitis B, Hib, pneumococcus or B. pertussis (history of laboratory confirmed, or clinical condition of paroxysmal cough for a period of longer than or equal to 2 weeks associated with apnea or whooping). Subjects who had household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis, B. pertussis, Hib, C. diphtheriae, polio, or pneumococcal infection at any time since birth. Subjects who had a history of anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component. Subjects who had experienced significant acute or chronic infection within the previous 7 days or have experienced fever (temperature ≥ 38.0°C [100.4°F]) within the previous 3 days. Subjects who had any serious acute or chronic disease, neurological disease including seizures, congenital defects, or cytogenic disorders (e.g., Down syndrome). Subjects who had a known or suspected autoimmune disease or persistent impairment/alteration of immune function. Subjects who had a suspected or known HIV infection or were born to a mother known to be HIV positive. Subjects who had ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation (including Hepatitis B immune globulin). Subjects who had a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. Subjects who with their parents/legal representatives were planning to leave the area of the study site before the end of the study period. Subjects who had any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives. Subjects who received any investigational agents or vaccines since birth or who expect to receive an investigational agent or vaccine prior to the completion of the study. Subjects who were relatives of site research staff working on this study.

Ages Eligible for Study
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Minimum Age: 55 Days
Maximum Age: 89 Days

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-CRM + Routine Vaccines<br>Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months of age. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months. | Biological: MenACWY-CRM<br>* One dose (0.5 mL) of MenACWY conjugate vaccine supplied as an extemporaneous mixing just before injection of the lyophilized component (MenA) reconstituted with the liquid component (MenCWY) was administered at 2, 4, 6 and 12 months of age as IM injections in the anterolateral area of the thigh.<br>Biological: DTaP-IPV/Hib<br>* IM injections of 3 doses of 0.5 mL each of DTaP-IPV/Hib supplied in prefilled vial were administered at 2, 4 and 6 months of age in the anterolateral area of the thigh.<br>* Other names: Combined diphtheria, tetanus toxoid, acellular pertussis and inactivated polio vaccine containing Haemophilus influenzae type B vaccine; Pentacel;Biological: HBV<br>* IM injections of 3 doses of 0.5 mL each of HBV supplied in prefilled vial were administered at 2, 4 and 6 months of age in the anterolateral area of the thigh.<br>* Other names: Hepatitis B virus vaccine; Engerix-B;Biological: PCV<br>* IM injections of 4 doses of 0.5 mL each of PCV supplied in prefilled vial were administered at 2, 4, 6 and 12 months of age in the anterolateral area of the thigh.<br>* Other names: Heptavalent Streptococcus pneumonia vaccine; Prevnar (PCV-7); Prevnar 13 (PCV-13);Biological: MMR<br>* Subcutaneous (SC) injection of 1 dose of 0.5 mL of MMR obtained by extemporaneous mixing just before injection of powder and the solvent for solution was administered at 12 months of age in the anterolateral area of the thigh.<br>* Other names: Measles, mumps, and rubella vaccine; M-M-R II;|
| Experimental: Routine Vaccines<br>Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months. In addition subjects were offered a dose of MenACWY-CRM at 18 months as a benefit of participating in this study. However, blood was not drawn for immunogenicity analysis after this dose. | Biological: DTaP-IPV/Hib<br>* IM injections of 3 doses of 0.5 mL each of DTaP-IPV/Hib supplied in prefilled vial were administered at 2, 4 and 6 months of age in the anterolateral area of the thigh.<br>* Other names: Combined diphtheria, tetanus toxoid, acellular pertussis and inactivated polio vaccine containing Haemophilus influenzae type B vaccine; Pentacel;Biological: HBV<br>* IM injections of 3 doses of 0.5 mL each of HBV supplied in prefilled vial were administered at 2, 4 and 6 months of age in the anterolateral area of the thigh.<br>* Other names: Hepatitis B virus vaccine; Engerix-B;Biological: PCV<br>* IM injections of 4 doses of 0.5 mL each of PCV supplied in prefilled vial were administered at 2, 4, 6 and 12 months of age in the anterolateral area of the thigh.<br>* Other names: Heptavalent Streptococcus pneumonia vaccine; Prevnar (PCV-7); Prevnar 13 (PCV-13);Biological: MMR<br>* Subcutaneous (SC) injection of 1 dose of 0.5 mL of MMR obtained by extemporaneous mixing just before injection of powder and the solvent for solution was administered at 12 months of age in the anterolateral area of the thigh.<br>* Other names: Measles, mumps, and rubella vaccine; M-M-R II;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA Titer ≥1:8 Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM | Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 against meningococcal serogroup A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), at baseline and one month after toddler dose of MenACWY-CRM administered at 12 months of age. The immune response was considered sufficient if the lower limit of the two-sided 95% confidence intervals (CIs) for the percentage of subjects with hSBA titer ≥1:8, at one month after toddler vaccination, was greater than 85% for the serogroup C, W, or Y and greater than 80% for the serogroup A. | Baseline and one month after fourth-dose of MenACWY-CRM | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hSBA Geometric Mean Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM | Immunogenicity was measured as the hSBA geometric mean titers (GMTs) directed against meningococcal serogroup A, C, W and Y, at baseline and one month after toddler dose of MenACWY-CRM administered at 12 months of age. | Baseline and one month after fourth-dose of MenACWY-CRM | 
| Percentage of Subjects With hSBA Titers ≥1:8, and Four-Fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Three Dose Infant Series Vaccination of MenACWY-CRM | Immunogenicity was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroup A, C, W and Y, before (baseline) and one month after 3 infant doses of MenACWY-CRM administered at 2, 4 and 6 months of age. Percentage of subjects who achieved at least four-fold rise in hSBA titers against serogroup A, C, W and Y was measured one month after 3 infant doses of MenACWY-CRM. | Baseline and one month after third infant dose of MenACWY-CRM | 
| hSBA Geometric Mean Titers Against Serogroup A, C, W and Y One Month After Three Dose Infant Series Vaccination of MenACWY-CRM | Immunogenicity was measured as the hSBA GMTs directed against meningococcal serogroups A, C, W and Y before (baseline) and one month after 3 infants doses of MenACWY-CRM administered at 2, 4 and 6 months of age. | Baseline and one month after third infant dose of MenACWY-CRM | 
| Percentage of Subjects With Seroresponse to Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone | The immune seroresponse to routine concomitant vaccination was measured as the percentages of subjects with pre-specified cut-off limit of ≥0.1 IU/mL (Diphtheria and Tetanus); ≥0.15 μg/mL (Hib); ≥0.35 μg/mL (Pneumococcal antigens, PnC); and ≥10 mIU/mL (Hepatitis B), evaluated using enzyme-linked immunosorbent assay (ELISA) at one month after 3 doses of infant series vaccination administered at 2, 4 and 6 months of age. The immune response to pertussis antigens (PT, FHA, Pertactin, FIM) was measured as percentage of subjects with seroresponse (in initially seronegative infants, ≥4 times the lower limit of quantification (LLQ); in initially seropositive infants, at least 4 times prevaccination concentration) by ELISA and percentage of subjects with titer ≥1:8 (Polio types 1, 2, and 3) by neutralization test (NT) one month after 3 doses of infant series vaccination administered at 2, 4 and 6 months of age. | One month after third dose of routine infant series vaccination | 
| Geometric Mean Concentrations Of Antibodies Against Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone | The immune response was measured as the geometric mean concentrations (GMCs) of antibodies directed against diphtheria, tetanus, pertussis (PT, FHA, Pertactin, FIM), hepatitis B, Hib, polio (type 1, 2 and 3) and pneumococcal (PnC 4, 6B, 9V, 14, 18C, 19F and 23F) antigens when routine vaccines are administered concomitantly with MenACWY-CRM compared with when routine vaccines are given alone, one month after 3 doses of infant series vaccination at 2, 4 and 6 months of age. | One month after third dose of routine infant series vaccination | 
| Geometric Mean Concentrations Of Antibodies Against Pneumococcal Antigens One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone | Immunogenicity was measured as the GMCs of anti-pneumococcal antibodies against pneumococcal antigens PnC 4, 6B, 9V, 14, 18C, 19F and 23F, one month after toddler dose of PCV at 12 months of age administered concomitantly with MenACWY-CRM compared with PCV given alone. | One month after PCV toddler vaccination | 
| Percentage of Subjects With Anti-pneumococcal Antigen Antibodies ≥0.35 μg/mL One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone | The immune seroresponse was measured as the percentage of subjects with anti-pneumococcal antigen antibodies ≥0.35 μg/mL against pneumococcal antigens PnC 4, 6B, 9V, 14, 18C, 19F and 23F, one month after toddler dose of PCV at 12 months of age when administered concomitantly with MenACWY-CRM compared with PCV given alone. | One month after PCV toddler vaccination | 
| Antibody Persistence by Percentage of Subjects With hSBA Titers ≥1:8 Against Serogroup A, C, W and Y, Six Months After Third Infant Vaccination, Prior to MenACWY-CRM Toddler Vaccination | The antibody persistence was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroup A, C, W and Y, at baseline and six months after third infant dose of MenACWY-CRM administered at 6 months (12 months of age), before administration of the toddler dose of MenACWY-CRM. | Baseline and Six months after third infant dose of MenACWY-CRM | 
| Persistence of hSBA Geometric Mean Titers Against Serogroup A, C, W and Y, Six Months After Third Infant Vaccination, Prior to MenACWY-CRM Toddler Vaccination | The antibody persistence was measured as the hSBA GMTs directed against meningococcal serogroup A, C, W and Y, at baseline and six months after third infant dose of MenACWY-CRM administered at 6 months (12 months of age), before administration of the toddler dose of MenACWY-CRM. | Baseline and Six months after third infant dose of MenACWY-CRM | 
| Percentage of Subjects With Four-fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM | The immune response was measured as the percentage of subjects who achieved four-fold increase in hSBA titers against meningococcal serogroup A, C, W and Y one month after toddler dose of MenACWY-CRM administered at 12 months of age as compared to hSBA titers before the toddler vaccination. | One month after MenACWY-CRM toddler vaccination | 
| Safety of MenACWY-CRM Vaccinations When Administered Concomitantly With Routine Vaccinations | Safety of the study vaccines (MenACWY-CRM and other routine vaccines) was assessed in terms of the number of subjects who reported adverse events (AEs) and/or serious AEs per vaccine group at the following time points: entire study period, after infants vaccination (up to 7 months), between 2- and 4-months, between 4- and 6-months, between 6- and 12-months, between 7- and 12-months, 28 days after 12-month vaccination, and between 29 days after 12-month vaccination and study termination. Solicited reactions were not collected during this study. The safety analyses also included any AEs observed by study personnel within 15 minutes following vaccination. All AEs and SAEs were judged by the investigator as whether probably related, possibly related, or not related to vaccine. | From day 1 to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MenACWY conjugate vaccine in infants, Meningococcal vaccine in infants, MenACWY