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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01000311




Registration number
NCT01000311
Ethics application status
Date submitted
22/10/2009
Date registered
23/10/2009
Date last updated
21/04/2014

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
V59_33
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Meningococcal Disease 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MenACWY-CRM
Other interventions - DTaP-IPV/Hib
Other interventions - HBV
Other interventions - PCV
Other interventions - MMR

Experimental: MenACWY-CRM + Routine Vaccines - 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.

Experimental: Routine Vaccines - 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.


Other interventions: MenACWY-CRM
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.

Other interventions: DTaP-IPV/Hib
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.

Other interventions: HBV
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.

Other interventions: PCV
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.

Other interventions: MMR
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.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and one month after fourth-dose of MenACWY-CRM
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and one month after fourth-dose of MenACWY-CRM
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline and one month after third infant dose of MenACWY-CRM
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline and one month after third infant dose of MenACWY-CRM
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
One month after third dose of routine infant series vaccination
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
One month after third dose of routine infant series vaccination
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
One month after PCV toddler vaccination
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
One month after PCV toddler vaccination
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline and Six months after third infant dose of MenACWY-CRM
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline and Six months after third infant dose of MenACWY-CRM
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
One month after MenACWY-CRM toddler vaccination
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
From day 1 to 18 months

Eligibility
Key inclusion criteria
1. Two month-old infants, born after a full-term pregnancy with an estimated gestational
age =37 weeks and a birth weight =2.5 kg.

2. Documented written informed consent provided by the parent/legal representative after
the nature of the study had been explained.

3. Parent/legal representative was available for all visits scheduled in the study.

4. Subjects were in good health as determined by:

1. medical history

2. physical assessment

3. clinical judgment of the investigator
Minimum age
55 Days
Maximum age
89 Days
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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.

2. 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).

3. 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.

4. Subjects who had a history of anaphylactic shock, asthma, urticaria or other allergic
reaction after previous vaccinations or known hypersensitivity to any vaccine
component.

5. 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.

6. Subjects who had any serious acute or chronic disease, neurological disease including
seizures, congenital defects, or cytogenic disorders (e.g., Down syndrome).

7. Subjects who had a known or suspected autoimmune disease or persistent
impairment/alteration of immune function.

8. Subjects who had a suspected or known HIV infection or were born to a mother known to
be HIV positive.

9. Subjects who had ever received blood, blood products and/or plasma derivatives or any
parenteral immunoglobulin preparation (including Hepatitis B immune globulin).

10. Subjects who had a known bleeding diathesis, or any condition that may be associated
with a prolonged bleeding time.

11. Subjects who with their parents/legal representatives were planning to leave the area
of the study site before the end of the study period.

12. Subjects who had any condition which, in the opinion of the investigator, might
interfere with the evaluation of the study objectives.

13. 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.

14. Subjects who were relatives of site research staff working on this study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
3 Sydney Children's Hospital Strasser Lab. Level 3 High Street - Randwick
Recruitment hospital [2] 0 0
2 Royal Children's Hospital Herston Road - Herston
Recruitment hospital [3] 0 0
1 Murdoch Childrens Research Institute C/- School of Population Health The University of Melbourne - Carlton
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3010 - Carlton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
West Virginia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Vaccines
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01000311
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications