Immunogenicity and Safety Study of Proquad® and Infanrix® Hexa When Administered Concomitantly (V221-035)

NCT00432042 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: V221-035X06-MMRV-3022006-004129-27
• Study Type: interventional
• Target: 955
• Locations: 2 countries
• Sites: 50

Brief Summary

Primary Objective:

• To demonstrate that ProQuad® can be administered concomitantly with a booster dose of Infanrix® hexa to healthy children 12 to 23 months of age without impairing either the antibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b; or to the 3 pertussis antibody titres measured at 42 days following vaccination. Secondary Objectives:
• To describe the antibody titres and the antibody response rates to measles, mumps, rubella, varicella, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b as measured at 42 days following vaccination by an Infanrix® hexa primary series schedule and all data are pooled.
• To evaluate the safety profile of ProQuad® when administered concomitantly with a booster dose of Infanrix® hexa by an Infanrix® hexa primary series schedule and all data are pooled.

Conditions

Varicella; Measles; Mumps; Rubella; Diphtheria; Tetanus; Pertussis; Poliomyelitis; Hepatitis B; Haemophilus Infections

Keywords

Mumps and Rubella; Haemophilus influenzae type b (Infanrix® hexa)

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (3)

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

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 \[PFU\]).

ProQuad®; ProQuad® + Infanrix® hexa

Infanrix® hexa BIOLOGICAL

Participants received a 0.5 mL intramuscular injection of Infanrix® hexa containing the following: diphtheria toxoid (≥30 IU), tetanus toxoid (≥40 IU), 3-component acellular pertussis (pertussis taxoid, filamentous haemagglutinin, and pertactin) (25 ug), Hepatitis B surface antigen recombinant (S protein) (10 ug), inactivated poliovirus types 1-3 (type 1: 40 D-antigen units; type 2: 8 D-antigen units; type 3: 32 D-antigen units), and Haemophilus influenzae type B (Hib) polysaccharide conjugate to tetanus toxoid (20-40 ug).

Infanrix® hexa; ProQuad® + Infanrix® hexa

Eligibility Criteria

• Age: 12 Months - 23 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy participants of either gender
• Aged 12 to 23 months
• No clinical history of measles, mumps, rubella, varicella and zoster
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (50)

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Alsfeld, Germany

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Bad Saulgau, Germany

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Bad Säckingen, Germany

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Bad Sobernheim, Germany

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Berlin, Germany

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Bielefeld, Germany

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Birkenfeld, Germany

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Bramsche, Germany

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Bretten, Germany

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Brunsbüttel, Germany

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Datteln, Germany

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Detmold, Germany

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Espelkamp, Germany

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Ettenheim, Germany

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Friedrichshafen, Germany

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Gerolstein, Germany

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Gifhorn, Germany

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Gütersloh, Germany

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Hamburg, Germany

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Heilbronn, Germany

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Herbolzheim, Germany

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Karlsruhe, Germany

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Kehl, Germany

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Koblenz, Germany

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Lauffen am Neckar, Germany

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Mannheim, Germany

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Marbach, Germany

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Mönchengladbach, Germany

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München, Germany

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Neustadt A.d. Aisch, Germany

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Nidderau, Germany

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Oberhausen, Germany

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Oberkirch, Germany

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Offenburg, Germany

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Pegnitz, Germany

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Rodorf, Germany

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Schwäbisch Hall, Germany

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Schwieberdingen, Germany

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Traunreut, Germany

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Veitshöchheim, Germany

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Wanzleben, Germany

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Welzheim, Germany

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Wildeshausen, Germany

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Zwiesel, Germany

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Chiavari, Italy

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Ferrara, Italy

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Latisana, Italy

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Ragusa, Italy

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Sassari, Italy

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Taranto, Italy

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Related Publications (1)

• 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.

  PMID: 25765966 DERIVED

MeSH Terms

Conditions

Chickenpox; Measles; Mumps; Rubella; Diphtheria; Tetanus; Whooping Cough; Poliomyelitis; Hepatitis B; Haemophilus Infections

Interventions

measles, mumps, rubella, varicella vaccine

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Rubulavirus Infections; Parotitis; Parotid Diseases; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Rubivirus Infections; Togaviridae Infections; Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Clostridium Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Pasteurellaceae Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Anne Fiquet, MD

  SPMSD

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2007
• First Posted: February 6, 2007
• Study Start: January 12, 2007
• Primary Completion: March 27, 2008
• Study Completion: March 27, 2008
• Last Updated: March 19, 2018
• Results First Posted: March 19, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6); DE (44)