Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Children in Their Second Year of Life

NCT01681992 | Completed Phase 3 Results

• 2 other identifiers: 1156492011-004905-26
• Study Type: interventional
• Target: 4,538
• Locations: 7 countries
• Sites: 81

Brief Summary

The purpose of this study is to evaluate end of shelf-life potency in terms of the immunogenicity and safety of GSK Biologicals' trivalent MMR vaccine, by comparing it to Merck \& Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).

Conditions

Measles; Mumps; Rubella; Measles-Mumps-Rubella Vaccine

Keywords

Safety; Measles, mumps and rubella diseases; Immunogenicity

Outcome Measures

Primary Outcomes (8)

• Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])

  For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration equal or above \[≥\] 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration less than \[\<\] 150 mIU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv\_MMR\_Min/Inv\_MMR\_Med vaccine in terms of seroresponse rate for measles virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv\_MMR\_Min/Inv\_MMR\_Med was to be ≥ 90% for antibodies to measles virus.

  At Day 42

• Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

  For mumps virus, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 5 EU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv\_MMR\_Min/Inv\_MMR\_Med vaccine in terms of seroresponse rate for mumps virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv\_MMR\_Min/Inv\_MMR\_Med was to be ≥ 90% for antibodies to mumps virus.

  At Day 42

• Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT])

  For mumps virus as measured by PRNT, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 4 End point Dilution 50% (ED50) (PRNT) among subjects who were seronegative (antibody concentration \< 2.5 ED50) before dose 1.

  At Day 42

• Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

  For rubella virus, a seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 4 IU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv\_MMR\_Min/Inv\_MMR\_Med vaccine in terms of seroresponse rate for rubella virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv\_MMR\_Min/Inv\_MMR\_Med was to be ≥ 90% for antibodies to mumps virus.

  At Day 42

• Anti-measles Virus Antibody Concentrations (by ELISA)

  Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.

  At Day 42

• Anti-mumps Virus Antibody Concentrations (by ELISA)

  Antibody concentrations were expressed as GMCs in EU/mL.

  At Day 42

• Anti-mumps Virus Antibody Concentrations (by PRNT)

  Antibody concentrations were expressed as Geometric Mean Titers (GMTs).

  At Day 42

• Anti-rubella Virus Antibody Concentrations (by ELISA)

  Antibody concentrations were expressed as GMCs in IU/mL.

  At Day 42

Secondary Outcomes (19)

• Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

  At Day 84

• Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

  At Day 84

• Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

  At Day 84

• Anti-measles Virus Antibody Concentrations (by ELISA)

  At Day 84

• Anti-mumps Virus Antibody Concentrations (by ELISA)

  At Day 84

Study Arms (3)

Inv_MMR_Min Group

EXPERIMENTAL

Subjects receive one dose of GlaxoSmithKline (GSK) Biologicals' measles, mumps, rubella (MMR) vaccine, Priorix (Inv\_MMR), from a minimum potency lot (Inv\_MMR\_Min), co-administered with Varivax (VV) and Havrix (HAV) vaccines at Day 0. All US subjects are also co-administered Prevnar 13 (PCV-13) vaccine. Approximately 6 weeks later, at Day 42, subjects are administered a dose from a separate lot of the Inv\_MMR vaccine (Inv\_MMR\_Release), for the second dose. Inv\_MMR and VV vaccines are administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively.

Biological: Priorix; Biological: Varivax; Biological: Havrix; Biological: Prevnar 13

Inv_MMR_Med Group

EXPERIMENTAL

Subjects receive one dose of GlaxoSmithKline (GSK) Biologicals' measles, mumps, rubella (MMR) vaccine, Priorix (Inv\_MMR), from a mid-range or medium potency lot (Inv\_MMR\_Med), co-administered with Varivax (VV) and Havrix (HAV) vaccines at Day 0. All US subjects are also co-administered Prevnar 13 (PCV-13) vaccine. Approximately 6 weeks later, at Day 42, subjects are administered a dose from a separate lot of the Inv\_MMR vaccine (Inv\_MMR\_Release), for the second dose. Inv\_MMR and VV vaccines are administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively.

Biological: Priorix; Biological: Varivax; Biological: Havrix; Biological: Prevnar 13

Com_MMR Group

ACTIVE COMPARATOR

Subjects receive one dose of M-M-R II (Com\_MMR) vaccine (Lot 1 or Lot 2), co-administered with Varivax (VV) and Havrix (HAV) vaccines at Day 0. All US subjects are also co-administered Prevnar 13 (PCV-13) vaccine. Approximately 6 weeks later, at Day 42, subjects are administered a dose of Com\_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com\_MMR and VV vaccines are administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively.

Biological: M-M-R II; Biological: Varivax; Biological: Havrix; Biological: Prevnar 13

Interventions

Priorix BIOLOGICAL

Subjects receive one dose of either minimum (Inv\_MMR\_Min) or medium (Inv\_MMR\_Med) potency lot at Day 0 and a dose of separate potency lot (Inv\_MMR\_Release) at Day 42, administered subcutaneously in the triceps region of the left arm.

Also known as: GSK Biologicals' live attenuated measles, mumps, rubella vaccine

Inv_MMR_Med Group; Inv_MMR_Min Group

M-M-R II BIOLOGICAL

Subjects receive two doses of either Lot 1 or Lot 2, one at Day 0 and one at Day 42, administered subcutaneously in the triceps region of the left arm.

Also known as: Merck & Co., Inc.'s measles, mumps, rubella virus vaccine, live

Com_MMR Group

Varivax BIOLOGICAL

Subjects receive one dose co-administered subcutaneously with the study vaccines (Priorix and M-M-R II), in the triceps region of right arm, at Day 0.

Also known as: Merck & Co., Inc.'s varicella virus vaccine, live

Com_MMR Group; Inv_MMR_Med Group; Inv_MMR_Min Group

Havrix BIOLOGICAL

Subjects receive one dose co-administered intramuscularly with the study vaccines (Priorix and M-M-R II), in the anterolateral region of the right thigh, at Day 0.

Also known as: GSK Biologicals' hepatitis A vaccine, inactivated

Com_MMR Group; Inv_MMR_Med Group; Inv_MMR_Min Group

Prevnar 13 BIOLOGICAL

US Subjects receive one dose co-administered intramuscularly with the study vaccines (Priorix and M-M-R II), in the anterolateral region of the left thigh, at Day 0.

Also known as: Pfizer Inc.'s pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein)

Com_MMR Group; Inv_MMR_Med Group; Inv_MMR_Min Group

Eligibility Criteria

• Age: 12 Months - 15 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male or female child between 12 and 15 months of age at the time of vaccination.
• The investigator believes that the parent(s) or Legally Acceptable Representative(s) (LAR(s)) of the child, can, and will comply with the requirements of the protocol.
• Written informed consent obtained from the parent(s)/LAR(s) of the child.
• Child is in stable health as determined by investigator's clinical examination and assessment of child's medical history.
• For US children only:
• Child that previously received a 3-dose series of Prevnar 13 with last dose at least 60 days prior to study entry.

You may not qualify if:

• Child in care.
• Use of any investigational or non-registered product other than the study vaccine(s) during the period starting 30 days before the day of study vaccination or planned use during the entire study period.
• Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product. Chronic administration of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose or any planned administration of immunosuppressive and immune-modifying drugs during the entire study.
• Inhaled and topical steroids are allowed.
• Planned administration / administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination at Visit 1 and ending at Visit 2 (or ending at Visit 3 for the US post-dose 2 sub-cohort). Please Note:
• Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time during the study, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s).
• Any age appropriate vaccine may be given starting at Visit 2 (or starting at Visit 3 for the US post-dose 2 sub-cohort), and anytime thereafter.
• Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to study vaccination at Visit 1 or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2, or at Visit 3 for the US post-dose 2 sub-cohort.
• History of measles, mumps, rubella, varicella/zoster and/or hepatitis A diseases.
• Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting 30 days prior to the first study vaccination.
• Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin, latex or gelatin.
• Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (81)

GSK Investigational Site

Birmingham, Alabama, 35205, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85012, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85032, United States

Location

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Little Rock, Arkansas, 72205, United States

Location

GSK Investigational Site

West Covina, California, 91790, United States

Location

GSK Investigational Site

Altamonte Springs, Florida, 32701, United States

Location

GSK Investigational Site

Miami, Florida, 33184, United States

Location

GSK Investigational Site

Miami Lakes, Florida, 33014, United States

Location

GSK Investigational Site

Naples, Florida, 34102, United States

Location

GSK Investigational Site

Tampa, Florida, 33606, United States

Location

GSK Investigational Site

Muncie, Indiana, 47304-5547, United States

Location

GSK Investigational Site

New Albany, Indiana, 47150, United States

Location

GSK Investigational Site

West Des Moines, Iowa, 50265, United States

Location

GSK Investigational Site

Wichita, Kansas, 67205, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40207, United States

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GSK Investigational Site

Annapolis, Maryland, 21401, United States

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GSK Investigational Site

Baltimore, Maryland, 21201, United States

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GSK Investigational Site

Frederick, Maryland, 21702, United States

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GSK Investigational Site

Kansas City, Missouri, 64108, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68504, United States

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GSK Investigational Site

Lincoln, Nebraska, 68505, United States

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GSK Investigational Site

Omaha, Nebraska, 68131, United States

Location

GSK Investigational Site

Clyde, North Carolina, 28721, United States

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GSK Investigational Site

Cleveland, Ohio, 44121, United States

Location

GSK Investigational Site

Dayton, Ohio, 45406, United States

Location

GSK Investigational Site

Dayton, Ohio, 45414, United States

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GSK Investigational Site

Toledo, Ohio, 43606, United States

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GSK Investigational Site

Youngstown, Ohio, 44514, United States

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GSK Investigational Site

Gresham, Oregon, 97030, United States

Location

GSK Investigational Site

Johnstown, Pennsylvania, 15904, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29406, United States

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GSK Investigational Site

Charleston, South Carolina, 29414, United States

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GSK Investigational Site

Houston, Texas, 77087, United States

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GSK Investigational Site

Layton, Utah, 84041, United States

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GSK Investigational Site

Springville, Utah, 84663, United States

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GSK Investigational Site

St. George, Utah, 84790, United States

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GSK Investigational Site

Midlothian, Virginia, 23113, United States

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GSK Investigational Site

Richmond, Virginia, 23223, United States

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GSK Investigational Site

Ellensburg, Washington, 98926, United States

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GSK Investigational Site

Benešov, 256 01, Czechia

Location

GSK Investigational Site

Chlumec nad Cidlinou, 50351, Czechia

Location

GSK Investigational Site

Děčín, 405 01, Czechia

Location

GSK Investigational Site

Jindřichův Hradec, 37701, Czechia

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GSK Investigational Site

Kladno, 272 01, Czechia

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GSK Investigational Site

Liberec, 46015, Czechia

Location

GSK Investigational Site

Lipník nad Bečvou, 75131, Czechia

Location

GSK Investigational Site

Náchod, 547 01, Czechia

Location

GSK Investigational Site

Odolena Voda, 25070, Czechia

Location

GSK Investigational Site

Ostrava - Poruba, 70800, Czechia

Location

GSK Investigational Site

Pardubice, 532 03, Czechia

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GSK Investigational Site

Prague, 1600, Czechia

Location

GSK Investigational Site

Helsinki, 00100, Finland

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GSK Investigational Site

Helsinki, 00930, Finland

Location

GSK Investigational Site

Jarvenpaa, 04400, Finland

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GSK Investigational Site

Oulu, 90220, Finland

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GSK Investigational Site

Tampere, 33100, Finland

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GSK Investigational Site

Turku, 20520, Finland

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GSK Investigational Site

Kuala Terengganu, 20400, Malaysia

Location

GSK Investigational Site

Kuching, 93586, Malaysia

Location

GSK Investigational Site

Sibu, 96000, Malaysia

Location

GSK Investigational Site

Guayama, 00784, Puerto Rico

Location

GSK Investigational Site

Ponce, 00716, Puerto Rico

Location

GSK Investigational Site

San Juan, 00936-5067, Puerto Rico

Location

GSK Investigational Site

Antequera/Málaga, 29200, Spain

Location

GSK Investigational Site

Barcelona, 08042, Spain

Location

GSK Investigational Site

Centelles (Barcelona), 08540, Spain

Location

GSK Investigational Site

L'Eliana, Valencia, 46183, Spain

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GSK Investigational Site

Manlleu, 08560, Spain

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GSK Investigational Site

Quart de Poblet, Valencia, 46930, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Seville, 41014, Spain

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GSK Investigational Site

Valencia, 46020, Spain

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GSK Investigational Site

Valencia, 46024, Spain

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GSK Investigational Site

Valencia, 46200, Spain

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GSK Investigational Site

Vic, 08500, Spain

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GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Bangkok, 10400, Thailand

Location

GSK Investigational Site

Bangkok, 10700, Thailand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

GSK Investigational Site

Pathum Thani, 12120, Thailand

Location

Related Publications (1)

• MMR-161 Study Group. Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12-15 months: A phase III, randomized, non-inferiority trial. Vaccine. 2018 Sep 11;36(38):5781-5788. doi: 10.1016/j.vaccine.2018.07.076. Epub 2018 Aug 10.

  PMID: 30104117 BACKGROUND

MeSH Terms

Conditions

Measles; Mumps; Rubella

Interventions

Measles-Mumps-Rubella Vaccine; Rubella Vaccine; Chickenpox Vaccine; Hepatitis A Vaccines; 13-valent pneumococcal vaccine; CRM197 (non-toxic variant of diphtheria toxin)

Condition Hierarchy (Ancestors)

Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Rubulavirus Infections; Parotitis; Parotid Diseases; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Rubivirus Infections; Togaviridae Infections

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Measles Vaccine; Viral Vaccines; Mumps Vaccine; Herpesvirus Vaccines; Viral Hepatitis Vaccines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 10, 2012
• Study Start: October 10, 2012
• Primary Completion: February 3, 2015
• Study Completion: August 18, 2015
• Last Updated: January 7, 2021
• Results First Posted: August 17, 2018

Record last verified: 2020-12

Locations

PR (3); MY (3); US (40); CZ (12); TH (5); ES (12); FI (6)