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

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

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.

Study Overview

• Status: Completed
• Conditions: Meningococcal Disease
• Intervention / Treatment: Biological: MenACWY-CRM; Biological: DTaP-IPV/Hib; Biological: HBV; Biological: PCV; Biological: MMR

• Study Type: Interventional
• Enrollment (Actual): 529
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • 3 Sydney Children's Hospital Strasser Lab. Level 3 High Street
  • Queensland
    • Herston, Queensland, Australia, 4029
      • 2 Royal Children's Hospital Herston Road
  • Victoria
    • Carlton, Victoria, Australia, 3010
      • 1 Murdoch Childrens Research Institute C/- School of Population Health The University of Melbourne
• Canada
  • Ontario
    • Sudbury, Ontario, Canada, P3E 1H5
      • 20 Medicor Research Inc 359 Riverside Suite 200
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • 37 Alabama Clinical Therapeutics LLC 52 Medical Park East Drive Suite 203
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • 15 Northwest Arkansas Pediatric Clinic 3383 N. Mana Court Suite 101
    • Jonesboro, Arkansas, United States, 72401
      • 6 Children's Clinic of Jonesboro AR 800 South Church Street Suite 400 and 204
  • California
    • Canoga Park, California, United States, 91306
      • 9 San Fernando Valley Research Associates 7111 Winnetka Avenue Suite 14
    • Fountain Valley, California, United States, 92708-5153
      • 17 Edinger Medical Group Research Center 9900 Talbert Avenue Suite 204
    • Madera, California, United States, 93637
      • 28 Madera Family Medical Group 1111 West 4th Street
    • Paramount, California, United States, 90723
      • 38 Center for Clinical Trials LLC 16660 Paramount Blvd Suite 301
  • Florida
    • Miami, Florida, United States, 33126
      • 8 Pharmax Research Clinic 7200 NW 7th Street Suite 350
  • Kansas
    • Topeka, Kansas, United States, 66604
      • 48 Cotton O'Neil Clinical Research Center 4100 SW 15th Street
    • Topeka, Kansas, United States, 66614
      • 47 Cotton O'Neil Clinical Research Center 6725 SW 29th Street
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • 29 Kentucky Pediatric/Adult Research 201 South 5th Street
    • Louisville, Kentucky, United States, 40291
      • 4 Nassim McMonigle Mescia and Associates 5512 Bardstown Road Suite 2
    • Louisville, Kentucky, United States, 40291
      • 40 Brownsboro Park Pediatrics 5512 Bardstown Road Suite 2
    • Louisville, Kentucky, United States, 40402
      • 24 University Of Louisville 555 South Floyd Street
    • Louisville, Kentucky, United States, 40402
      • 26 University Of Louisville 230 East Broadway
    • Springfield, Kentucky, United States, 40069
      • 30 Kentucky Pediatric/Adult Research 102 West Depot Street
  • Louisiana
    • Haughton, Louisiana, United States, 71037
      • 27 Ark-La-Tex Children's Clinic 1025 Highway 80 E
    • Shreveport, Louisiana, United States, 71105
      • 13 Willis Knighton Physician Network- Portico Pediatrics 7847 Youree Drive
  • Michigan
    • Niles, Michigan, United States, 49120
      • 35 Southwestern Medical Clinic P.C. 2002 S 11th Street
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • 25 Center for Pharmaceutical Research 1010 Carondelet Drive Suite 426
  • Ohio
    • Cleveland, Ohio, United States, 44121-4243
      • 31 Senders Pediatrics 2054 South Green Road
    • Dayton, Ohio, United States, 45406
      • 5 Dayton Clinical Research 1100 Salem Ave.
    • Huber Heights, Ohio, United States, 45424
      • 14 Ohio Pediatrics Research Association 7371 Brandt Pike Suite C
    • Kettering, Ohio, United States, 45420
      • 22 Ohio Pediatrics Research Association 1775 Delco Park Drive
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74127
      • 45 Oklahoma State University Physicians 635 W 11th St
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • 33 Primary Physicians Research Inc. 1580 McLaughlin Run Road
    • Pittsburgh, Pennsylvania, United States, 15241
      • 34 Primary Physicians Research Inc. 1580 McLaughlin Run Road
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • 10 Holston Medical Group 105 W. Stone Drive Suite 3B
    • Lebanon, Tennessee, United States, 37087
      • 23 Focus Research Group 201 Signature Place
  • Texas
    • Amarillo, Texas, United States, 79124
      • 7 Amarillo Children's Clinical Research #17 Care Circle
    • Houston, Texas, United States, 77070
      • 46 Pediatric Healthcare of Northwest Houston P.A. 12015 Louetta Road Suite 100
    • Tomball, Texas, United States, 77375
      • 12 Pediatric Healthcare of Northwest Houston P.A. 13406 Medical Complex Drive Suite 200
  • Utah
    • Clinton, Utah, United States, 84015
      • 16 Westside Medical 1477 North 2000 West
    • Layton, Utah, United States, 84041
      • 42 Wee Care Pediatrics 934 S. Main Street Suite 8
    • Layton, Utah, United States, 84041
      • 43 Wee Care Pediatrics 1580 W. Antelope Drive Suite 100
    • Provo, Utah, United States, 84604
      • 19 Pediatric Care 1675 North Freedom Blvd Building 3
    • Roy, Utah, United States, 84067
      • 44 Wee Care Pediatrics 5991 S. 3500 W Suite 100 Rock Run Plaza
    • South Jordan, Utah, United States, 84095
      • 18 Copperview Medical Center 3556 West 9800 South
    • St. George, Utah, United States, 84790
      • 39 Dixie Pediatrics 1240 E 100 S Suite 14
    • Syracuse, Utah, United States, 84075
      • 41 Wee Care Pediatrics 1792 W. 1700 S. Suite 102
  • Virginia
    • Richmond, Virginia, United States, 23219
      • 36 Dominion Medical Associates 304 East Leigh Street
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • 21 CAMC Health Education and Research Institute 3100 McCorkle Ave. S.E. Suite 806

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.; Biological: 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 Names: Combined diphtheria, tetanus toxoid, acellular pertussis and inactivated polio vaccine containing Haemophilus influenzae type B vaccine; Pentacel; Biological: 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 Names: Hepatitis B virus vaccine; Engerix-B; Biological: 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 Names: Heptavalent Streptococcus pneumonia vaccine; Prevnar (PCV-7); Prevnar 13 (PCV-13); Biological: 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.; Other Names: Measles, mumps, and rubella vaccine; M-M-R II
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.	Biological: 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 Names: Combined diphtheria, tetanus toxoid, acellular pertussis and inactivated polio vaccine containing Haemophilus influenzae type B vaccine; Pentacel; Biological: 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 Names: Hepatitis B virus vaccine; Engerix-B; Biological: 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 Names: Heptavalent Streptococcus pneumonia vaccine; Prevnar (PCV-7); Prevnar 13 (PCV-13); Biological: 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.; Other Names: Measles, mumps, and rubella vaccine; M-M-R II

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: October 22, 2009
• First Submitted That Met QC Criteria: October 22, 2009
• First Posted (Estimate): October 23, 2009

Study Record Updates

• Last Update Posted (Estimate): April 21, 2014
• Last Update Submitted That Met QC Criteria: April 3, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: MenACWY; MenACWY conjugate vaccine in infants; Meningococcal vaccine in infants
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V59_33