Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants

Study Overview
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Brief Summary
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The primary objective of this phase 3b study is to evaluate the safety and tolerability of Novartis MenACWY conjugate vaccine when administered with routine infant vaccinations to healthy infants

Official Title
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A Phase 3b, Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants

Conditions
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Meningitis, Meningococcal Infection

Intervention / Treatment
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* Biological: MenACWY-CRM197
* Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine
* Biological: Hib (Haemophilus influenza b) Vaccine
* Biological: IPV (Inactivated Polio Vaccine) Vaccine
* Biological: Pneumococcal conjugate Vaccine
* Biological: MMR (Measles, Mumps, and Rubella) Vaccine
* Biological: Varicella Vaccine
* Biological: Hepatitis A Virus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy 2-month-old infants (aged 55 - 89 days); babies must have been born after a full-term pregnancy with an estimated gestation age ≥37 weeks and a birth weight ≥2.5 kg for whom a parent/legal representative has given written informed consent after the nature of the study has been explained; who are available for all visits scheduled in the study; who are in good health as determined by medical history and physical assessment. Exclusion Criteria: who previously received any meningococcal vaccine or D, T, P, IPV or OPV, H influenzae type b (Hib) or Pneumococcus; prior doses of BCG (one) and/or HBV (two) are permitted who have 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); 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; who have a history of anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component; who have experienced significant acute or chronic infection within the previous 7 days or have experienced fever (axillary temperature ≥ 38.0°C [100.4°F]) within the previous 3 days; who have any present or suspected serious acute (e.g. leukemia, lymphomas), or chronic disease (e.g., with signs of cardiac disease, renal failure, severe malnutrition, or insulin dependent diabetes), or progressive neurological disease, or a genetic anomaly/known cytogenic disorders (e.g., Down's syndrome); who have a known or suspected autoimmune disease or persistent impairment/alteration of immune function resulting from (for example): receipt of any immunosuppressive therapy at any time since birth receipt of immunostimulants at any time since birth receipt of any systemic corticosteroid since birth; who have a suspected or known HIV infection or HIV related disease; who have ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation; who have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time; who have any history of seizure; who with their parents/legal representatives are planning to leave the area of the study site before the end of the study period; who have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives; who have 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. who are 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-CRM197 + Routine Vaccines (Non-Detailed)<br>Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR: 12 months. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Non-Detailed - infants who only provided SAEs (Serious Adverse Events) and medically attended AEs (Adverse Events). | Biological: MenACWY-CRM197<br>* Four 0.5mL vaccinations of MenACWY-CRM197 conjugate vaccine was administered by intramuscular injection at 2, 4, 6 and 12 months of age.<br>Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine<br>* Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.<br>Biological: Hib (Haemophilus influenza b) Vaccine<br>* Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.<br>Biological: IPV (Inactivated Polio Vaccine) Vaccine<br>* Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.<br>Biological: Pneumococcal conjugate Vaccine<br>* Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.<br>Biological: MMR (Measles, Mumps, and Rubella) Vaccine<br>* One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.<br>|
| Active Comparator: Routine Vaccines (Non-Detailed)<br>Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR: 12 months. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Non-Detailed - subjects who only provided SAEs and medically attended AEs. | Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine<br>* Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.<br>Biological: Hib (Haemophilus influenza b) Vaccine<br>* Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.<br>Biological: IPV (Inactivated Polio Vaccine) Vaccine<br>* Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.<br>Biological: Pneumococcal conjugate Vaccine<br>* Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.<br>Biological: MMR (Measles, Mumps, and Rubella) Vaccine<br>* One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.<br>|
| Experimental: MenACWY-CRM197 + Routine Vaccines (Detailed)<br>Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs. | Biological: MenACWY-CRM197<br>* Four 0.5mL vaccinations of MenACWY-CRM197 conjugate vaccine was administered by intramuscular injection at 2, 4, 6 and 12 months of age.<br>Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine<br>* Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.<br>Biological: Hib (Haemophilus influenza b) Vaccine<br>* Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.<br>Biological: IPV (Inactivated Polio Vaccine) Vaccine<br>* Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.<br>Biological: Pneumococcal conjugate Vaccine<br>* Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.<br>Biological: MMR (Measles, Mumps, and Rubella) Vaccine<br>* One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.<br>Biological: Varicella Vaccine<br>* One vaccination of Varicella vaccine was administered at 12 months of age.<br>Biological: Hepatitis A Virus<br>* One vaccination of Hepatitis A Virus vaccine was administered at 12 months of age.<br>|
| Active Comparator: Routine Vaccines (Detailed)<br>Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs. | Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine<br>* Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.<br>Biological: Hib (Haemophilus influenza b) Vaccine<br>* Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.<br>Biological: IPV (Inactivated Polio Vaccine) Vaccine<br>* Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.<br>Biological: Pneumococcal conjugate Vaccine<br>* Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.<br>Biological: MMR (Measles, Mumps, and Rubella) Vaccine<br>* One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.<br>Biological: Varicella Vaccine<br>* One vaccination of Varicella vaccine was administered at 12 months of age.<br>Biological: Hepatitis A Virus<br>* One vaccination of Hepatitis A Virus vaccine was administered at 12 months of age.<br>|
| Experimental: MenACWY-CRM197 + Routine Vaccines (All)<br>Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. All (Detailed and Non-Detailed subjects): Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs; Non-Detailed - subjects who only provided SAEs and medically attended AEs. | Biological: MenACWY-CRM197<br>* Four 0.5mL vaccinations of MenACWY-CRM197 conjugate vaccine was administered by intramuscular injection at 2, 4, 6 and 12 months of age.<br>Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine<br>* Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.<br>Biological: Hib (Haemophilus influenza b) Vaccine<br>* Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.<br>Biological: IPV (Inactivated Polio Vaccine) Vaccine<br>* Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.<br>Biological: Pneumococcal conjugate Vaccine<br>* Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.<br>Biological: MMR (Measles, Mumps, and Rubella) Vaccine<br>* One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.<br>Biological: Varicella Vaccine<br>* One vaccination of Varicella vaccine was administered at 12 months of age.<br>Biological: Hepatitis A Virus<br>* One vaccination of Hepatitis A Virus vaccine was administered at 12 months of age.<br>|
| Active Comparator: Routine Vaccines (All)<br>Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. All (Detailed and Non-Detailed subjects): Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs; Non-Detailed - subjects who only provided SAEs and medically attended AEs. | Biological: DTaP (Diptheria, Tetanus, Pertussis) Vaccine<br>* Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.<br>Biological: Hib (Haemophilus influenza b) Vaccine<br>* Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.<br>Biological: IPV (Inactivated Polio Vaccine) Vaccine<br>* Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.<br>Biological: Pneumococcal conjugate Vaccine<br>* Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.<br>Biological: MMR (Measles, Mumps, and Rubella) Vaccine<br>* One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.<br>Biological: Varicella Vaccine<br>* One vaccination of Varicella vaccine was administered at 12 months of age.<br>Biological: Hepatitis A Virus<br>* One vaccination of Hepatitis A Virus vaccine was administered at 12 months of age.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination | To compare the percentages of subjects who reported at least one severe systemic reaction after any vaccination of MenACWY-CRM197 (detailed) plus routine vaccines (detailed) group to that observed in the routine vaccines alone (detailed) group administered at 2, 4, 6, and 12 months of age. Detailed - infants who provided reactogenicity and all Adverse Events (AEs) for 7 days, Serious Adverse Events (SAEs) and medically attended AEs. | 15 minutes to Day 7 after any vaccination administered at 2, 4, 6 and 12 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period | To compare the percentages of subjects presenting at least one serious adverse event (SAE) through 6 months post-final dose in subjects who received MenACWY-CRM197 vaccine concomitantly with routine vaccinations to the percentages of subjects who received routine vaccinations alone. | Day 1 (2 months of age) to 18 months of age | 
| Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | To compare the percentage of subjects who reported local and systemic solicited adverse events from day 1 to day 7 after each vaccination with MenACWY-CRM197 given concomitantly with routine vaccinations to the routine vaccinations alone group. | 15 minutes to Day 7 | 
| Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Safety data with medically attended events were collected throughout the study in the non-detailed safety groups and from Day 8 onwards for the detailed safety groups. | Day 1 (2 months of age) to 18 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, infants, healthy, meningitis, meningococcal