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

Meningococcal Disease Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01000311
• Other study ID #: V59_33
• Status: Completed
• Phase: Phase 3
• First received: October 22, 2009
• Last updated: April 3, 2014
• Start date: November 2009
• Est. completion date: November 2011

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 529
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Days to 89 Days

Eligibility

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

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Meningococcal Disease
• Meningococcal Infections

Intervention

Biological:
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	1 Murdoch Childrens Research Institute C/- School of Population Health The University of Melbourne	Carlton	Victoria
Australia	2 Royal Children's Hospital Herston Road	Herston	Queensland
Australia	3 Sydney Children's Hospital Strasser Lab. Level 3 High Street	Randwick	New South Wales
Canada	20 Medicor Research Inc 359 Riverside Suite 200	Sudbury	Ontario
United States	7 Amarillo Children's Clinical Research #17 Care Circle	Amarillo	Texas
United States	29 Kentucky Pediatric/Adult Research 201 South 5th Street	Bardstown	Kentucky
United States	37 Alabama Clinical Therapeutics LLC 52 Medical Park East Drive Suite 203	Birmingham	Alabama
United States	9 San Fernando Valley Research Associates 7111 Winnetka Avenue Suite 14	Canoga Park	California
United States	21 CAMC Health Education and Research Institute 3100 McCorkle Ave. S.E. Suite 806	Charleston	West Virginia
United States	31 Senders Pediatrics 2054 South Green Road	Cleveland	Ohio
United States	16 Westside Medical 1477 North 2000 West	Clinton	Utah
United States	5 Dayton Clinical Research 1100 Salem Ave.	Dayton	Ohio
United States	15 Northwest Arkansas Pediatric Clinic 3383 N. Mana Court Suite 101	Fayetteville	Arkansas
United States	17 Edinger Medical Group Research Center 9900 Talbert Avenue Suite 204	Fountain Valley	California
United States	27 Ark-La-Tex Children's Clinic 1025 Highway 80 E	Haughton	Louisiana
United States	46 Pediatric Healthcare of Northwest Houston P.A. 12015 Louetta Road Suite 100	Houston	Texas
United States	14 Ohio Pediatrics Research Association 7371 Brandt Pike Suite C	Huber Heights	Ohio
United States	6 Children's Clinic of Jonesboro AR 800 South Church Street Suite 400 and 204	Jonesboro	Arkansas
United States	25 Center for Pharmaceutical Research 1010 Carondelet Drive Suite 426	Kansas City	Missouri
United States	22 Ohio Pediatrics Research Association 1775 Delco Park Drive	Kettering	Ohio
United States	10 Holston Medical Group 105 W. Stone Drive Suite 3B	Kingsport	Tennessee
United States	42 Wee Care Pediatrics 934 S. Main Street Suite 8	Layton	Utah
United States	43 Wee Care Pediatrics 1580 W. Antelope Drive Suite 100	Layton	Utah
United States	23 Focus Research Group 201 Signature Place	Lebanon	Tennessee
United States	24 University Of Louisville 555 South Floyd Street	Louisville	Kentucky
United States	26 University Of Louisville 230 East Broadway	Louisville	Kentucky
United States	4 Nassim McMonigle Mescia and Associates 5512 Bardstown Road Suite 2	Louisville	Kentucky
United States	40 Brownsboro Park Pediatrics 5512 Bardstown Road Suite 2	Louisville	Kentucky
United States	28 Madera Family Medical Group 1111 West 4th Street	Madera	California
United States	8 Pharmax Research Clinic 7200 NW 7th Street Suite 350	Miami	Florida
United States	35 Southwestern Medical Clinic P.C. 2002 S 11th Street	Niles	Michigan
United States	38 Center for Clinical Trials LLC 16660 Paramount Blvd Suite 301	Paramount	California
United States	33 Primary Physicians Research Inc. 1580 McLaughlin Run Road	Pittsburgh	Pennsylvania
United States	34 Primary Physicians Research Inc. 1580 McLaughlin Run Road	Pittsburgh	Pennsylvania
United States	19 Pediatric Care 1675 North Freedom Blvd Building 3	Provo	Utah
United States	36 Dominion Medical Associates 304 East Leigh Street	Richmond	Virginia
United States	44 Wee Care Pediatrics 5991 S. 3500 W Suite 100 Rock Run Plaza	Roy	Utah
United States	13 Willis Knighton Physician Network- Portico Pediatrics 7847 Youree Drive	Shreveport	Louisiana
United States	18 Copperview Medical Center 3556 West 9800 South	South Jordan	Utah
United States	30 Kentucky Pediatric/Adult Research 102 West Depot Street	Springfield	Kentucky
United States	39 Dixie Pediatrics 1240 E 100 S Suite 14	St. George	Utah
United States	41 Wee Care Pediatrics 1792 W. 1700 S. Suite 102	Syracuse	Utah
United States	12 Pediatric Healthcare of Northwest Houston P.A. 13406 Medical Complex Drive Suite 200	Tomball	Texas
United States	47 Cotton O'Neil Clinical Research Center 6725 SW 29th Street	Topeka	Kansas
United States	48 Cotton O'Neil Clinical Research Center 4100 SW 15th Street	Topeka	Kansas
United States	45 Oklahoma State University Physicians 635 W 11th St	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes