Meningococcal Disease, Meningococcal Meningitis
Conditions
Keywords
Meningococcal disease, vaccines, toddlers, prevention, Meningitis
Brief summary
The study was to evaluate the safety and and immune response of each of three lots of Novartis Meningococcal C Conjugate Vaccine (MenC-CRM Liquid) when administered to Healthy Toddlers.
Interventions
BIOLOGICALMenC-CRM LIQ
One dose of MenC-CRM vaccine, liquid formulation
BIOLOGICALMenC-CRM ROS
One dose of MenC-CRM vaccine, lyophilized formulation produced with drug substance manufactured at Rosia, Italy.
BIOLOGICALMenC-CRM EMV
One dose of MenC-CRM vaccine, lyophilized formulation produced with drug substance manufactured at Emeryville, USA.
Sponsors
Novartis Vaccines
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 23 Months
Healthy volunteers
Yes
Inclusion criteria
1. Healthy 12 - 23 (inclusive) month-old male or female toddlers. 2. A parent/legal guardian was given written informed consent after the nature of the study has been explained. 3. Available for both the visits scheduled in the study. 4. In good health as determined by medical history, physical examination and clinical judgment of the investigator.
Exclusion criteria
1. History of any meningococcal vaccine administration. 2. Previous known or suspected disease caused by N. meningitidis. 3. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection or colonization. 4. History of severe allergic reaction after previous vaccinations, allergy to Latex, or hypersensitivity to any component of the vaccine. 5. Significant acute or chronic infection within the previous 7 days or axillary temperature ≥38.0°C within the previous 3 days. 6. Individuals who have received antibiotics within 6 days before vaccination. 7. Known or suspected autoimmune disease or impairment/alteration of the immune system resulting from (for example): * Receipt of any immunosuppressive therapy at any time since birth. * Receipt of any immunostimulants at any time since birth. * Receipt of any systemic corticosteroids or chronic use of inhaled high-potency corticosteroids since birth (use of topical corticosteroids administered in limited areas of the body \[for example, eczema on knees or face or elbows\] is allowed). * Immune deficiency disorder, or known HIV infection. 8. History of seizure, any progressive neurological disease or Guillain Barré Syndrome (exception: one self-limited non-medicated febrile seizure is acceptable). 9. Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 10. Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks. 11. Taken any antipyretic medication in the previous 6 hours. 12. Received any other vaccines within 30 days prior to enrollment or intent to receive any other vaccine during the study (Exception: Inactivated influenza vaccine may be administered up to 15 days prior to study immunization and no less than 15 days after study immunization). 13. Toddler's parent(s) or legal guardian(s) are not able to comprehend and to follow all required study procedures for the whole period of the study. 14. Participation in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study during this study. 15. Family members or household members of site research staff. 16. History or any illness/condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study. 17. Any serious chronic or progressive disease according to judgment of the investigator (neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | 1 month postvaccination (day 29) | Immunogenicity was measured by human serum bactericidal activity (hSBA) geometric mean titers (GMTs)against N meningitidis type C, at day 29 after a single vaccination when administered to toddlers to assess the equivalence of MenC-CRM LIQ to MenC-CRM EMV and MenC-CRM ROS to MenC-CRM EMV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean hSBA Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | 1 month postvaccination (day 29) | Immunogenicity was measured by hSBA GMTs against N meningitidis type C, approximately 28 days (at day 29) after a single vaccination when administered to toddlers to assess the equivalence of MenC-CRM LIQ to MenC-CRM ROS. |
| Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | From day 1 through day 7 | Safety was assessed as the number of subjects who reported solicited local and systemic adverse events following a single injection with either MenC-CRM LIQ or MenC-CRM ROS or MenC-CRM EMV. Safety was also assessed in subjects who mistakenly received MenC-CRM EMV instead of MenC-CRM ROS. |
Countries
Poland
Participant flow
Recruitment details
Subjects were enrolled at eleven sites in Poland.
Pre-assignment details
All enrolled subjects were included in the trial. Data from the group MenC-CRM ROS\_EMV was not included in the primary and secondary analyses as these subjects were initially enrolled in group MenC-CRM ROS, but wrongly vaccinated with MenC-CRM EMV.
Participants by arm
| Arm | Count |
|---|---|
| MenC-CRM LIQ Subjects received 1 injection of MenC-CRM vaccine, liquid formulation. | 299 |
| MenC-CRM ROS Subjects received 1 injection of MenC-CRM vaccine, lyophilized formulation produced with drug substance manufactured at Rosia, Italy. | 268 |
| MenC-CRM EMV Subjects received 1 injection of MenC-CRM vaccine, lyophilized formulation produced with drug substance manufactured at Emeryville, USA. | 306 |
| MenC-CRM ROS_EMV Subjects enrolled to receive MenC-CRM ROS, but were mistakenly administered 1 injection of MenC-CRM EMV | 119 |
| Total | 992 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | MenC-CRM LIQ | MenC-CRM ROS | MenC-CRM EMV | MenC-CRM ROS_EMV | Total |
|---|---|---|---|---|---|
| Age, Continuous | 16.4 Months STANDARD_DEVIATION 3.4 | 16.2 Months STANDARD_DEVIATION 3.2 | 16.7 Months STANDARD_DEVIATION 3.4 | 17.2 Months STANDARD_DEVIATION 3.3 | 16.5 Months STANDARD_DEVIATION 3.3 |
| Sex: Female, Male Female | 143 Participants | 131 Participants | 141 Participants | 50 Participants | 465 Participants |
| Sex: Female, Male Male | 156 Participants | 137 Participants | 165 Participants | 69 Participants | 527 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 252 / 299 | 227 / 267 | 236 / 304 | 88 / 119 |
| serious Total, serious adverse events | 0 / 299 | 3 / 267 | 2 / 304 | 1 / 119 |
Outcome results
Primary
Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination
Immunogenicity was measured by human serum bactericidal activity (hSBA) geometric mean titers (GMTs)against N meningitidis type C, at day 29 after a single vaccination when administered to toddlers to assess the equivalence of MenC-CRM LIQ to MenC-CRM EMV and MenC-CRM ROS to MenC-CRM EMV.
Time frame: 1 month postvaccination (day 29)
Population: Analysis was done on the per protocol (PP) set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenC-CRM LIQ | Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 1 | 2.1 Titers |
| MenC-CRM LIQ | Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 29 | 9.84 Titers |
| MenC-CRM ROS | Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 1 | 2.16 Titers |
| MenC-CRM ROS | Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 29 | 14 Titers |
| MenC-CRM EMV | Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 1 | 2.15 Titers |
| MenC-CRM EMV | Geometric Mean Human Serum Bactericidal Activity Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 29 | 12 Titers |
Comparison: The study would be considered a success if the two-sided 95% confidence intervals (CIs) for the hSBA GMT ratios comparing MenC-CRM LIQ to MenC-CRM EMV at 28 days after a single vaccination were both within the equivalence interval (0.5, 2.0).p-value: <0.0595% CI: [0.67, 1]ANOVA
Comparison: The study would be considered a success if the two-sided 95% confidence intervals (CIs) for the hSBA GMT ratios comparing MenC-CRM ROS to MenC-CRM EMV at 28 days after a single vaccination were both within the equivalence interval (0.5, 2.0).p-value: <0.0595% CI: [0.92, 1.41]ANOVA
Secondary
Geometric Mean hSBA Titers Against N Meningitidis Serogroup C 28 Days After Vaccination
Immunogenicity was measured by hSBA GMTs against N meningitidis type C, approximately 28 days (at day 29) after a single vaccination when administered to toddlers to assess the equivalence of MenC-CRM LIQ to MenC-CRM ROS.
Time frame: 1 month postvaccination (day 29)
Population: Analysis was done on the per protocol (PP) set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenC-CRM LIQ | Geometric Mean hSBA Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 1 | 2.1 Titers |
| MenC-CRM LIQ | Geometric Mean hSBA Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 29 | 9.84 Titers |
| MenC-CRM ROS | Geometric Mean hSBA Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 1 | 2.16 Titers |
| MenC-CRM ROS | Geometric Mean hSBA Titers Against N Meningitidis Serogroup C 28 Days After Vaccination | Day 29 | 14 Titers |
Comparison: The secondary objective was to be assessed only if both primary objectives were met. Because of this, no adjustment for multiplicity was required. MenC-CRM liquid would be declared equivalent to MenC-CRM ROS if the two-sided 95% CI for the ratio of the hSBA GMTs at approximately 28 days following vaccination was within the equivalence interval (0.5, 2.0).p-value: <0.0595% CI: [0.58, 0.89]ANOVA
Secondary
Number Of Subjects Reporting Solicited Local And Systemic Adverse Events
Safety was assessed as the number of subjects who reported solicited local and systemic adverse events following a single injection with either MenC-CRM LIQ or MenC-CRM ROS or MenC-CRM EMV. Safety was also assessed in subjects who mistakenly received MenC-CRM EMV instead of MenC-CRM ROS.
Time frame: From day 1 through day 7
Population: Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Diarrhea | 42 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Sleepiness | 66 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Induration | 252 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Vomiting | 9 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Local | 124 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Irritability | 101 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Systemic | 163 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Fever (≥38°C) | 20 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Erythema | 222 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Persistent Crying | 45 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Change in Eating habits | 87 Number of subjects |
| MenC-CRM LIQ | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Tenderness | 88 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Change in Eating habits | 68 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Tenderness | 64 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Vomiting | 11 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Persistent Crying | 41 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Erythema | 200 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Local | 115 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Irritability | 76 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Induration | 227 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Sleepiness | 55 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Systemic | 140 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Fever (≥38°C) | 11 Number of subjects |
| MenC-CRM ROS | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Diarrhea | 30 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Persistent Crying | 36 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Local | 148 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Tenderness | 101 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Erythema | 211 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Induration | 236 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Systemic | 155 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Change in Eating habits | 83 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Sleepiness | 56 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Vomiting | 7 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Diarrhea | 34 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Irritability | 87 Number of subjects |
| MenC-CRM EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Fever (≥38°C) | 18 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Change in Eating habits | 26 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Systemic | 60 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Any Local | 58 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Diarrhea | 17 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Induration | 88 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Erythema | 81 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Fever (≥38°C) | 13 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Irritability | 32 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Persistent Crying | 15 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Sleepiness | 24 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Injection site Tenderness | 41 Number of subjects |
| MenC-CRM ROS_EMV | Number Of Subjects Reporting Solicited Local And Systemic Adverse Events | Vomiting | 4 Number of subjects |