Immunogenicity and Safety Study of Proquad® and Infanrix®... | NCT00432042

ID	Type	Description	Link
X06-MMRV-302	Other Identifier	Sanofi Pasteur MSD Protocol Number
2006-004129-27	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
ProQuad® + Infanrix® hexa	Experimental	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).	Biological: ProQuad® Biological: Infanrix® hexa
ProQuad®	Active Comparator	Pediatric (12 to 23 months of age) participants received ProQuad® on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).	Biological: ProQuad®
Infanrix® hexa	Active Comparator	Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).	Biological: Infanrix® hexa

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ProQuad®	Biological	Participants received a 0.5 mL subcutaneous injection of ProQuad® containing the following live attenuated virus strains: measles virus Enders' Edmonston strain (≥3.00 log10 50% cell culture infectious dose [CCID]50), mumps virus Jeryl Lynn™ (Level B) strain (≥4.30 log10 CCID50), rubella virus Wistar RA 27/3 strain (≥3.00 log10 CCID50), and varicella virus Oka/Merck strain (≥3.99 log10 plaque-forming units [PFU]).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella	The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 2: ProQuad® was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre <255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre <10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre <10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre <1.25 gpELISA units/mL. Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA).	Day 42
Percentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B	The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: Hepatitis B antibody titre ≥10 IU/mL and Haemophilus Influenzae Type b antibody titre ≥1 ug/mL. Hepatitis B antibody levels were determined using anti-HBs ORTHO ECi Immunodiagnostic Assay. Haemophilus Influenzae Type b antibody (anti-polyribosylribitol phosphate [PRP]) levels were determined with radioimmunoassay (RIA) or with enzyme immunoassay (EIA).	Day 42
Post-vaccination Geometric Mean Titres (GMT) to Pertussis	The GMT to pertussis were compared in Arm1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa. Anti-pertussis toxin (anti-PT), anti-filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) were determined using ELISA on solid phase based on sandwich principle.	Day 42

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy participants of either gender
Aged 12 to 23 months
No clinical history of measles, mumps, rubella, varicella and zoster
For Italy: Primary vaccination with the combined diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine Infanrix® hexa as a 2-dose schedule, with receipt of the second dose ≥ 6 months prior to inclusion
For Germany: Primary vaccination with the combined diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine Infanrix® hexa as a 3-dose schedule, with receipt of the third dose ≥ 6 months prior to inclusion
Consent form signed by parent(s) according to local regulations or by the legal representative properly informed about the study
Parent(s)/legal representative able to understand the protocol requirements and to fill in the Diary Card.

Exclusion Criteria:

Prior receipt of measles, mumps, rubella and/or varicella vaccine either alone or in any combination
Any recent (<= 30 days) exposure to measles, mumps, rubella, varicella and/or zoster
Receipt of any other diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and/or Haemophilus influenzae type b containing vaccine (either alone or in any combination) than Infanrix® hexa
Any recent (<= 3 days) history of febrile illness
Any severe chronic disease
Active untreated tuberculosis
Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition
Any known blood dyscrasia, leukemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic or lymphatic systems
Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection
Prior known sensitivity/allergy to any component of the vaccines including neomycin, sorbitol or gelatin
Any immune impairment or humoral/cellular deficiency, neoplastic disease or depressed immunity
Any recent (<= 2 days) tuberculin test or scheduled tuberculin test through Visit 2
Any previous (<= 150 days) receipt of immune serum globulin or any blood-derived products or scheduled to be administered through Visit 2
Any recent (<= 30 days) receipt of an inactivated or a live non-study vaccine or scheduled non-study vaccination through Visit 2
Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
Any recent (≤30 days) participation or scheduled participation in any other clinical trial through Visit 2

Name	Affiliation	Role
Anne Fiquet, MD	SPMSD	Study Director

PubMed Identifier	Type	Citation	Retractions
25765966	Derived	Deichmann KA, Ferrera G, Tran C, Thomas S, Eymin C, Baudin M. Immunogenicity and safety of a combined measles, mumps, rubella and varicella live vaccine (ProQuad (R)) administered concomitantly with a booster dose of a hexavalent vaccine in 12-23-month-old infants. Vaccine. 2015 May 11;33(20):2379-86. doi: 10.1016/j.vaccine.2015.02.070. Epub 2015 Mar 9.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm 1: ProQuad® + Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
FG001	Arm 2: ProQuad®

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm 1: ProQuad® + Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
BG001	Arm 2: ProQuad®	Pediatric (12 to 23 months of age) participants received ProQuad® on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
BG002	Arm 3: Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella

The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 2: ProQuad® was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre <255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre <10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre <10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre <1.25 gpELISA units/mL. Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA).

Participants in Arm 1 and Arm 2 who were initially seronegative to measles, mumps, rubella, or varicella; had post-vaccination serology results; and who did not have protocol violations that may have interfered with immunogenicity results were included. As analysis of Arm 3 was not planned it was not included.

Posted

Number

95% Confidence Interval

Percentage of Participants

Day 42

ID	Title	Description
OG000	Arm 1: ProQuad® + Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
OG001	Arm 2: ProQuad®	Pediatric (12 to 23 months of age) participants received ProQuad® on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).

Units	Counts
Participants	OG000431 OG001215

Title

Denominators

Categories

Measles

- ParticipantsOG000421
- ParticipantsOG001215

Title	Measurements
	OG00097.4(95.4 to 98.7)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Mean Difference (Final Values)	1.14			2-Sided	95	-1.62	4.82			Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is > -10%.		Non-Inferiority or Equivalence	Measles difference
OG000 OG001

Primary

Percentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B

The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: Hepatitis B antibody titre ≥10 IU/mL and Haemophilus Influenzae Type b antibody titre ≥1 ug/mL. Hepatitis B antibody levels were determined using anti-HBs ORTHO ECi Immunodiagnostic Assay. Haemophilus Influenzae Type b antibody (anti-polyribosylribitol phosphate [PRP]) levels were determined with radioimmunoassay (RIA) or with enzyme immunoassay (EIA).

Participants in Arm 1 and Arm 3 who had post-vaccination serology results and who did not have protocol violations that may have interfered with immunogenicity results were included. As analysis of Arm 2 was not planned it was not included.

Posted

Number

95% Confidence Interval

Percentage of participants

Day 42

ID	Title	Description
OG000	Arm 1: ProQuad® + Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
OG001	Arm 3: Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).

Primary

Post-vaccination Geometric Mean Titres (GMT) to Pertussis

The GMT to pertussis were compared in Arm1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa. Anti-pertussis toxin (anti-PT), anti-filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) were determined using ELISA on solid phase based on sandwich principle.

Posted

Number

95% Confidence Interval

GMT (IU/mL)

Day 42

ID	Title	Description
OG000	Arm 1: ProQuad® + Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).
OG001	Arm 3: Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1: ProQuad® + Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).	7	474	409	474
EG001	Arm 2: ProQuad®	Pediatric (12 to 23 months of age) participants received ProQuad® on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).	6	234	134	234
EG002	Infanrix® Hexa	Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).	4	239	184	239

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected474 at risk EG0013 events3 affected234 at risk EG0021 events1 affected239 at risk
Bronchopneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected474 at risk EG0011 events1 affected234 at risk EG0020 events0 affected239 at risk
Conjunctivitis bacterial	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected474 at risk EG0011 events1 affected234 at risk EG0020 events0 affected239 at risk
Gastroenteritis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected474 at risk EG0010 events0 affected234 at risk EG0020 events0 affected239 at risk
Gastroenteritis rotavirus	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected474 at risk EG0011 events1 affected234 at risk EG0021 events1 affected239 at risk
Influenza	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected474 at risk EG0010 events0 affected234 at risk EG0021 events1 affected239 at risk
Otitis media	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected474 at risk EG0010 events0 affected234 at risk EG0020 events0 affected239 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected474 at risk EG0011 events1 affected234 at risk EG0020 events0 affected239 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected474 at risk EG0010 events0 affected234 at risk EG0020 events0 affected239 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected474 at risk EG0010 events0 affected234 at risk EG0020 events0 affected239 at risk
Electric shock	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected474 at risk EG0010 events0 affected234 at risk EG0021 events1 affected239 at risk
Febrile convulsion	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected474 at risk EG0010 events0 affected234 at risk EG0020 events0 affected239 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00023 events22 affected474 at risk EG00114 events14 affected234 at risk EG00214 events14 affected239 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00015 events14 affected474 at risk EG0012 events2 affected234 at risk EG00215 events14 affected239 at risk
Injection site erythema	General disorders	MedDRA 10.0	Systematic Assessment	EG000338 events274 affected474 at risk EG00131 events31 affected234 at risk EG002131 events126 affected239 at risk
Injection site pain	General disorders	MedDRA 10.0	Systematic Assessment	EG000285 events198 affected474 at risk EG00133 events33 affected234 at risk EG00284 events84 affected239 at risk
Injection site swelling	General disorders	MedDRA 10.0	Systematic Assessment	EG000235 events203 affected474 at risk EG0017 events7 affected234 at risk EG00293 events93 affected239 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG000263 events184 affected474 at risk EG001104 events80 affected234 at risk EG00291 events68 affected239 at risk
Bronchitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00028 events27 affected474 at risk EG00112 events12 affected234 at risk EG00212 events12 affected239 at risk
Nasopharyngitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00050 events48 affected474 at risk EG00116 events14 affected234 at risk EG00218 events18 affected239 at risk
Rhinitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00028 events27 affected474 at risk EG00123 events20 affected234 at risk EG00210 events9 affected239 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00032 events31 affected474 at risk EG00115 events13 affected234 at risk EG00211 events11 affected239 at risk
Rash morbilliform	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00036 events33 affected474 at risk EG00116 events16 affected234 at risk EG0026 events5 affected239 at risk

Ancestor Terms

ID	Term
D000073618	Varicella Zoster Virus Infection
D006566	Herpesviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D018185	Morbillivirus Infections
D018184	Paramyxoviridae Infections
D018701	Mononegavirales Infections
D012327	RNA Virus Infections
D019351	Rubulavirus Infections
D010309	Parotitis
D010305	Parotid Diseases
D012466	Salivary Gland Diseases
D009059	Mouth Diseases
D009057	Stomatognathic Diseases
D018355	Rubivirus Infections
D014036	Togaviridae Infections
D003354	Corynebacterium Infections
D000193	Actinomycetales Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D003015	Clostridium Infections
D001885	Bordetella Infections
D016905	Gram-Negative Bacterial Infections
D012141	Respiratory Tract Infections
D012140	Respiratory Tract Diseases
D009187	Myelitis
D002494	Central Nervous System Infections
D004769	Enterovirus Infections
D010850	Picornaviridae Infections
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D013118	Spinal Cord Diseases
D000090862	Neuroinflammatory Diseases
D009468	Neuromuscular Diseases
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D018347	Hepadnaviridae Infections
D006525	Hepatitis, Viral, Human
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D016871	Pasteurellaceae Infections

Facility	Status	City	State	ZIP	Country	Contacts
		Alsfeld			Germany

ID	Term
D002644	Chickenpox
D008457	Measles
D009107	Mumps
D012409	Rubella
D004165	Diphtheria
D013742	Tetanus
D014917	Whooping Cough
D011051	Poliomyelitis
D006509	Hepatitis B
D006192	Haemophilus Infections