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

Meningitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00806195
• Other study ID #: V59P23
• Status: Completed
• Phase: Phase 3
• First received: December 9, 2008
• Last updated: May 13, 2013
• Start date: December 2008
• Est. completion date: November 2011

Study information

• Verified date: May 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7744
• Est. completion date: November 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Days to 89 Days

Eligibility

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):

1. receipt of any immunosuppressive therapy at any time since birth

2. receipt of immunostimulants at any time since birth

3. 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.

Study Design

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

Related Conditions & MeSH terms

• Meningitis
• Meningococcal Infection
• Meningococcal Infections

Intervention

Biological:
• MenACWY-CRM197
Four 0.5mL vaccinations of MenACWY-CRM197 conjugate vaccine was administered by intramuscular injection at 2, 4, 6 and 12 months of age.
• DTaP (Diptheria, Tetanus, Pertussis) Vaccine
Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.
• Hib (Haemophilus influenza b) Vaccine
Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.
• IPV (Inactivated Polio Vaccine) Vaccine
Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.
• Pneumococcal conjugate Vaccine
Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.
• MMR (Measles, Mumps, and Rubella) Vaccine
One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.
• Varicella Vaccine
One vaccination of Varicella vaccine was administered at 12 months of age.
• Hepatitis A Virus
One vaccination of Hepatitis A Virus vaccine was administered at 12 months of age.

Locations

Country	Name	City	State
China	304 Department of Pediatrics, Chang Gung Children's Hospital 12F, L Building, #5, Fu-Shin St.	Kweishan, Taoyuan 333	Taiwan
China	301 Department of Pediatrics, National Taiwan University Hospital, 15F,Children's Hospital, No. 8 Chung Shan S. Rd,	Taipei	Taiwan
China	302 Department of Pediatrics, Mackay Memorial Hospital No. 92, Sec. 2, ChangShan Road,	Taipei	Taiwan
China	303 Department of Pediatrics, Taiwan Adventist Hospital 424, Sec 2, Pa-Te Road,	Taipei	Taiwan
Costa Rica	401 Clínica Pediátrica Calle 20 Ave 0 y 2 Costado Oeste del Hospital Nacional de Niños - segundo piso,	San José
Costa Rica	402 Centro Integral Medico 25 m Oeste e la Junta de Protección Social,	San José
Costa Rica	404 Instituto de Atención Pediátrica (IAP) Del Restaurante La Bastilla, 50m Sur, Paseo Colón	San José
Costa Rica	403 Centro Médico San Vicente 125m Este de la entrada Principal de Emergencia del Hospital	San Vicente de Paul, Heredia
Guatemala	503 Clínica para Niños 6a Avenida 6-63 Zona 10, Edificio Sixtino, Oficina 305, Tercer Nivel,	Guatemala City	Guatemala CP01010
Guatemala	504 Clínica Periférica El Amparo II, 38 Calle 31-89, Zona 7 Colonia El Amparo II,	Guatemala City	Guatemala. CP 01007
Guatemala	506 Health Center 4ª Avenida 16-72 Zona 10,	Guatemala City	Guatemala CP01010
Guatemala	508 Unidad de Crecimiento y Desarrollo, Clínica del Niño Sano, Hospital Roosevelt 6ª Avenida 3-10 Zona 11, Ingreso Principal Hospital Roosevelt	Guatemala City	Guatemala CP. 01011
Guatemala	501 Hospital Infantil de Infectología y Rehabilitación 9ª. Avenida 7-01 Zona 11 Colonia Roosevelt,	Guatemala City,
Guatemala	502 Clínica Privada 6a Avenida 3-22 Zona 10, Centro Médico II, Ofic. 601	Guatemala City,	Guatemala CP01010
Guatemala	507 Clínica Médica Privada Edificio Multimédica, 2 calle 25-19 Zona 15	Vista Hermosa I	Guatemala CP 01015
Panama	601 Hospital Materno Infantil José Domingo De Obaldía, Centro para la Investigación y Desarrollo de Estudios Clínicos Vía Panamericana, San Pablo viejo, David,	Chiriquí
Panama	602 Centro Pediátrico América, Consultorio América Segundo Piso Consultorio No. 223, Vía España, Carrasquilla, Frente al Hospital de Especialidades Pediátricas	Ciudad de Panamá
Panama	603 Policentro Luis H. Moreno, Parque Lefevre	Via Cincuentenario
Peru	704 Hospital Nacional Docente Madre Niño San Bartolomé Av. Alfonso Ugarte 825,	Cercado de Lima	Lima 01
Peru	701 Instituto de Investigación Nutricional - Anexo Huáscar, SJL Manzana 122, Lote 21, Grupo 15	Huascar, San Juan de Lurigancho	Lima 36
Peru	708 Hospital Nacional Guillermo Almenara Irigoyen Av. Grau No. 800, La Victoria, Lima 13	Lima
Peru	703 Hospital María Auxiliadora Av. Miguel Iglesias 968, San Juan de Miraflores,	Lima 29
Peru	705 Hospital Nacional Cayetano Heredia Av. Honorio Delgado No. 262, Urbanización Ingeniería, San Martín de Porres	Lima 31
United States	97 Children's Hospital Medical Center of Akron One Perkins Square	Akron	Ohio
United States	64 Amarillo Childrens Clinical Research #17 Care Circle	Amarillo	Texas
United States	95 Heartland Research Associates 510 West Radio Lane	Arkansas City	Kansas
United States	120 Akron Children's Hospital Pediatrics 62 Conservatory Drive, #A	Barberton	Ohio
United States	51 Kentucky Pediatric/Adult Research 201 S. 5th Street	Bardstown	Kentucky
United States	83 The Portland Clinic LLP 15950 SW Millikan Lane Research Dept.	Beaverton	Oregon
United States	55 Central Arkansas Pediatric Clinic Pediatric 2301 Springhill Road Suite 200	Benton	Arkansas
United States	6 Alabama Clinical Therapeutics 806 St. Vincent's Drive, Ste 615	Birmingham	Alabama
United States	22 Roslindale Pediatric Assoc, P.C 1153 Centre St Suite 31	Boston	Massachusetts
United States	75 Pediatric Care 1596 S. 500 W., 1st Floor	Bountiful	Utah
United States	80 Craig A. Spiegel, M.D 12255 DePaul Drive Sutie 380	Bridgeton	Missouri
United States	173 Maimonides Medical Center 948 48th Street 1st Floor	Brooklyn	New York
United States	179 Associated Pharmaceutical Research Center, Inc 8615 Knott Avenue Suite 5	Buena Park	California
United States	160 San Fernando Valley Research Associates, Inc. 7111 Winnetka Ave. #14	Canoga Park	California
United States	56 Cary Pediatrics 1001 Crescent Green Dr.	Cary	North Carolina
United States	41 Palmetto Pediatrics, PA Pediatrics 2781 Tricom Street	Charleston	South Carolina
United States	85 Pediatric Research of Charlottesville, LLC 1011 East Jefferson St. Suite 3	Charlottesville	Virginia
United States	36 Dr. Senders and Associates, Pediatrics 2054 South Green Road	Cleveland	Ohio
United States	162 North Georgia Clinical Research Center 1575 Chattanooga Avenue Suite 1	Dalton	Georgia
United States	79 Dayton Clinical Research 1100 Salem Ave	Dayton	Ohio
United States	Northern Illinois Research Associates 625 E. Bethany Ste. 3	Dekalb	Illinois
United States	157 Universal Biopharma Research Institute Inc./Alta Family Health Clinic 888 N. Alta Ave.	Dinuba	California
United States	43 Alabama Clinical Therapeutics, LLC 364 Honeysuckle Rd	Dothan	Alabama
United States	1 Premier Health Research Center, LLC 11525 Brookshire Ave Suite 400	Downey	California
United States	103 Durham Pediatrics 2609 North Duke Street, Suite 1000	Durham	North Carolina
United States	104 Regional Pediatrics 4022 Freedom Lake Drive	Durham	North Carolina
United States	13 Duke Health Center 4020 N. Roxboro Road	Durham	North Carolina
United States	113 Children's Health Care-West 4671 West Lake Road	Erie	Pennsylvania
United States	37 Pediatric Associates of Fairfield, Inc. 5900 Boymel Drive	Fairfield	Ohio
United States	23 Pediatric Associates of Fall River 829 South Main Street	Fall River	Massachusetts
United States	87 Innovis Health 1702 South University Drive Suite 1	Fargo	North Dakota
United States	21 Northwest Arkansas Pediatric Clinic 3383 N. MANA Court Suite 101	Fayetteville	Arkansas
United States	30 Sparks Pediatric Clinic 1501 S. Waldron Road Suite 100	Fort Smith	Arkansas
United States	19 University of North Texas Health Science Center 3500 Camp Bowie Blvd	Fort Worth	Texas
United States	68 Sierra Medical Research 5150 N. Sixth, Suite 156	Fresno	California
United States	175 Sealy Center for Vaccine Development, Clinical Trials 301 University Blvd. Children's Hospital Room 3.270F L#20412	Galveston	Texas
United States	82 Dixie Pediatrics 1240 E 100 S STE 14 St.	George	Utah
United States	109 UPMC/Community Medicine Inc. 90 Shenango Street	Greenville	Pennsylvania
United States	7 Cyn3rgy Research 24850 SE Stark Street Suite 180	Gresham	Oregon
United States	107 Pennridge Pediatric Associates 270 Main Street	Harleysville,	Pennsylvania
United States	132 Kaiser Permanente Pediatric - Mapunapuna 2828 Paa Street, 2nd Floor	Honolulu	Hawaii
United States	96 West Houston Clinical Research Service 2026 Wirt Road	Houston	Texas
United States	4 Ohio Pediatrics, INC 7371 Brandt Pike Suite C	Huber Heights	Ohio
United States	14 The Children's Clinic of Jonesboro 800 S. Church Suite 400	Jonesboro	Arkansas
United States	102 Ohio Pediatrics, INC 1775 Delco Park Drive	Kettering	Ohio
United States	71 Holston Medical Group 105 W. Stone Dr. Suite 2A	Kingsport	Tennessee
United States	72 Holston Medical Group 2033 Meadowview Lane	Kingsport	Tennessee
United States	129 Citrus Vally Family Practice 1400 Hacienda Blvd	La Puente	California
United States	99 Altamonte Pediatric Associates 101 N Country Club Rd.	Lake Mary	Florida
United States	69 Clinical Research Center of Nevada 1012 East Sahara Avenue	Las Vegas	Nevada
United States	115 Wee Care(Layton) 1580 West Antelope Drive	Layton	Utah
United States	116 Wee Care(Kaysville) 934 South Main Street, Suite 8	Layton	Utah
United States	165 Focus Research Group 201 Signature Place Suite C	Lebanon	Tennessee
United States	84 Michael W. Simon M.D. 185 Pasadena Drive Suite 220	Lexington	Kentucky
United States	170 Little Rock Children's Clinic P.A. 9600 Lile Dr., Ste 360	Little Rock	Arkansas
United States	3 Arkansas Pediatric Clinic 500 S. University Suite 200	Little Rock	Arkansas
United States	70 Summer Pediatrics 4811 Buckley Road	Liverpool	New York
United States	114 Loma Linda University Health 11175 Campus Street Coleman Pavillion A-1120	Loma Linda	California
United States	59 Loma Linda University Health 11175 Campus Street Coleman Pavillion A-1120	Loma Linda	California
United States	153 Health Care Partners Medical Group Health Care Partners Medical Group 4401 Atlantic Ave.	Long Beach	California
United States	94 Health Care Partners Medical Group 1025 W. Olympic Blvd.	Los Angeles	California
United States	106 University Child Health Specialists 230 East Broadway	Louisville	Kentucky
United States	24 Bluegrass Clinical Research, Inc 5512 Bardstown Road Suite 2	Louisville	Kentucky
United States	76 Bluegrass Clinical Research, Inc 5512 Bardstown Road Suite2	Louisville	Kentucky
United States	67 Madera Family Medical Group 1111 West 4th Street	Madera	California
United States	11 Pediatrics and Adolescent Medicine, PA 2155 Post Oak Tritt Road Suite 100	Marietta	Georgia
United States	158 Huguenot Pediatrics, PC 1407 Huguenot Rd.	Midlothian	Virginia
United States	16 Winthrop University Hospital Department of Pediatrics 120 Mineola Blvd Suite 210	Mineola	New York
United States	181 Jean Brown Research 164 East 5900 South Suite A-112	Murray	Utah
United States	52 Heritage Medical Associates 2325 Crestmoor Road	Nashville	Tennessee
United States	92 Heartland Research Associates LLC 700 Medical Center Dr. Suite 210	Newton	Kansas
United States	168 Southwestern Medical Clinic 2002 South 11th Street	Niles	Michigan
United States	126 North Andover Pediatrics Associates 800 Turnpike Street	North Andover	Massachusetts
United States	29 Norwich Pediatric Group 92 New London Turnpike	Norwich	Connecticut
United States	121 Kaiser Permanente (Oakland) 3505 Broadway 6th floor	Oakland	California
United States	63 Kaiser Permanente Vaccine Study Center One Kaiser Plaza 16th Floor	Oakland	California
United States	42 Children's Hospital of Orange County 455 S. Main Street	Orange	California
United States	60 Orlando Health Pediatric Faculty Practice 32 West Sturtevant St, MP-141	Orlando	Florida
United States	15 University of Louisville 571 South Floyd Suite 321 L	Ouisville	Kentucky
United States	34 Pediatric Partners Pediatrics 3401 PGA Blvd Ste 300	Palm Beach Gardens	Florida
United States	12 Center For Clinical Trials, LLC. 16660 Paramount Blvd Suite 301	Paramount	California
United States	110 Pediatric Alliance Southwestern - Squirrel Hill 4070 Beechwood Blvd	Pittsburgh	Pennsylvania
United States	112 Pediatric Alliance, Southwestern 850 Clairton Blvd	Pittsburgh	Pennsylvania
United States	118 Pediatric Alliance, PC Arcadia Division 9000 Perry Highway Suite 120	Pittsburgh	Pennsylvania
United States	5 Primary Physicians Research, Inc 1580 McLaughlin Run Road	Pittsburgh	Pennsylvania
United States	122 Kaiser Permanente (Pleasanton) 7601 Stoneridge Drive, MOB North 2nd Floor	Pleasanton	California
United States	74 Utah Valley Pediatrics North University 7407 North Cedar St.	Provo	Utah
United States	48 Capitol Pediatrics and Adolescent Center 3801 Computer Drive Suite 200	Raleigh	North Carolina
United States	91 Triangle Medical Research 5816 Creedmoor Rd. Suite 104	Raleigh	North Carolina
United States	46 Virginia Commonwealth University 1001 East Marshall Street P008	Richmond	Virginia
United States	117 Wee Care(Roy) 5991 South 3500 West, Suite 100	Roy	Utah
United States	57 UC Davis Medical Center 2516 Stockton Blvd Ticon II	Sacramento	California
United States	61 Foothill Family Clinic South 6360 South 300 East Suite 100	Salt Lake City	Utah
United States	66 J. Lewis Research Inc. 2295 Foothill Drive	Salt Lake City	Utah
United States	31 Southwest Children's Research Associates, P. A. 5282 Medical Drive Suite 311	San Antonio	Texas
United States	50 San Antonio Metropolitan Health District 332 West Commerce Room 307	San Antonio	Texas
United States	123 Kaiser Permanente (San Francisco) 2200 O'Farrell Street 6th floor room 636	San Francisco	California
United States	166 Buena Salud Pediatrics 2880 Story Road	San Jose	California
United States	88 Physician Care Clinical Research 1918 Robinhood Street	Sarasota	Florida
United States	49 Pennridge Pediatric Associates 711 Lawn Avenue	Sellersville	Pennsylvania
United States	86 Willis-Knighton Physician Network 7847 Youree Drive	Shreveport	Louisiana
United States	151 Family First Pediatrics c/o Pharmaceutical Research Organization 1268 W. South Jordan Parkway Suite 201	South Jordan	Utah
United States	2 Rockwood Clinical Research Center 400 East Fifth Avenue	Spokane	Washington
United States	38 Rockwood Clinic, P.S. 9001 N. Country Homes Blvd.	Spokane	Washington
United States	108 Physicians to Children and Adolescents 102 West Depot Street	Springfield	Kentucky
United States	89 Aspen Medical Group 1020 Bandana Blvd West Ste 214	St. Paul	Minnesota
United States	90 Premier Medical Group Alpha Clinical Research 279 Clear Sky Court	Ste C Clarksville	Tennessee
United States	26 Southwestern Medical Clinic 5515 Cleveland Avenue Suite 1	Stevensville	Michigan
United States	44 Wee Care Pediatrics (Syracuse) 1792 West 1700 South Suite 102	Syracuse	Utah
United States	77 SUNY Upstate Medical University 750 East Adams Street Suite 5400	Syracuse	New York
United States	54 1st International Research Centers 10370 Steeke Street	Thornton	Colorado
United States	47 Dynamed Clinical Research 13406 Medical Complex Dr Suite 200	Tomball	Texas
United States	178 Pediatric Care 6725 Southwest Twenty-Ninth Street	Topeka	Kansas
United States	152 Health Care Partners Medical Group 3565 Del Amo Blvd Research Dept.	Torrance	California
United States	20 White Memorial Pediatric Medical Group UCLA Center for Vaccine Research 1124 West Carson Street Liu Research Building (Room 132)	Torrance	California
United States	25 Oklahoma State University-CHS C/O Pediatrics 635 West 11th Street	Tulsa	Oklahoma
United States	81 Cholla Pediatrics 2167 West Orange Grove Road	Tuscon	Arizona
United States	124 The Vancouver Clinic/NE 87th Avenue 700 NE 87th Avenue	Vancouver	Washington
United States	125 The Vancouver Clinic/Columbia Tech Center 501 SE 172th Avenue	Vancouver	Washington
United States	167 The Vancouver Clinic/Salmon Creek 2525 NE 139th Street	Vancouver	Washington
United States	93 Advanced Pediatrics 100 East Street SE Suite 301	Vienna	Virginia
United States	131 Kaiser Permanente Waipio 1st Floor 94-1480 Moaniani Street	Waipahu	Hawaii
United States	163 Wenatchee Valley Medical Center Clinical Research Department 820 North Chelan Avenue	Wenatchee	Washington
United States	40 Center for Clinical Trials of San Gabriel 1300 S Sunset Avenue Suite 101	West Covina	California
United States	Jordan Ridge Kids & Teens 8822 S. Redwood Road Suite S103	West Jordan	Utah
United States	73 Piedmont Medical Research Assoc 1901 S Hawthorne Rd Ste 306	Winston-Salem	North Carolina
United States	9 Woburn Pediatric Associates 7 Alfred Street Baldwin Park II	Woburn	Massachusetts
United States	101 Pediatrics and Adolescent Medicine, PA 120 Stonebridge Parkway, Suite 410	Woodstock	Georgia
United States	100 Pediatric Associates of Youngstown 727 East Western Reserve Road	Youngstown	Ohio
United States	28 Pediatric Associates of Youngstown 4308 Belmont Avenue	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	Novartis Vaccines

Countries where clinical trial is conducted

United States,  China,  Costa Rica,  Guatemala,  Panama,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes