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Trial record 4 of 11 for:    "Rubella" | "Heptavalent Pneumococcal Conjugate Vaccine"

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

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ClinicalTrials.gov Identifier: NCT01681992
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : August 17, 2018
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE September 6, 2012
First Posted Date  ICMJE September 10, 2012
Results First Submitted Date  ICMJE December 30, 2016
Results First Posted Date  ICMJE August 17, 2018
Last Update Posted Date August 17, 2018
Actual Study Start Date  ICMJE October 10, 2012
Actual Primary Completion Date February 3, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2018)
  • Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) [ Time Frame: At Day 42 ]
    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.
  • Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) [ Time Frame: At Day 42 ]
    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.
  • Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) [ Time Frame: At Day 42 ]
    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.
  • Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) [ Time Frame: At Day 42 ]
    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.
  • Anti-measles Virus Antibody Concentrations (by ELISA) [ Time Frame: At Day 42 ]
    Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
  • Anti-mumps Virus Antibody Concentrations (by ELISA) [ Time Frame: At Day 42 ]
    Antibody concentrations were expressed as GMCs in EU/mL.
  • Anti-mumps Virus Antibody Concentrations (by PRNT) [ Time Frame: At Day 42 ]
    Antibody concentrations were expressed as Geometric Mean Titers (GMTs).
  • Anti-rubella Virus Antibody Concentrations (by ELISA) [ Time Frame: At Day 42 ]
    Antibody concentrations were expressed as GMCs in IU/mL.
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2012)
Immunogenicity of the MMR vaccines [ Time Frame: At Day 42 ]
Seroresponses for MMR are defined as a post-vacc., anti-virus Ab conc. in children who were seronegative pre-vacc. as follows: For measles virus, a post-vacc. anti-measles virus Ab conc. of ≥200 mIU/mL (ELISA) in children <150 mIU/mL pre-vacc.; For mumps virus, a post-vacc. anti-mumps virus Ab conc. ≥10 EU/mL (ELISA) in children <5 EU/mL pre-vacc.; For mumps virus as measured by PRNT, a post-vacc. anti-mumps virus Ab conc. ≥4 ED50 (PRNT) in children <2.5 ED50 before Dose 1; For rubella virus, a post-vacc. anti-rubella virus Ab conc. ≥10 IU/mL (ELISA) in children <4 IU/mL pre-vacc.
Change History Complete list of historical versions of study NCT01681992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2018)
  • Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) [ Time Frame: At Day 84 ]
    For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥ 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration < 150 mIU/mL) before dose 1.
  • Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) [ Time Frame: At Day 84 ]
    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.
  • Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) [ Time Frame: At Day 84 ]
    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.
  • Anti-measles Virus Antibody Concentrations (by ELISA) [ Time Frame: At Day 84 ]
    Antibody concentrations were expressed as GMCs in mIU/mL.
  • Anti-mumps Virus Antibody Concentrations (by ELISA) [ Time Frame: At Day 84 ]
    Antibody concentrations were expressed as GMCs in EU/mL.
  • Anti-rubella Virus Antibody Concentrations (by ELISA) [ Time Frame: At Day 84 ]
    Antibody concentrations were expressed as GMCs in IU/mL.
  • Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ]
    Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects With Any Solicited Local AEs Post Dose 2 [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ]
    Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects With Any Solicited General AEs Post Dose 1 [ Time Frame: During the 15-day (Days 0-14) post-vaccination period ]
    Assessed solicited general AEs were drowsiness, irritability/fussiness and loss of appetite. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any Fever Post Dose 1 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Any fever = Fever (axillary) ≥ 38°C.
  • Number of Subjects Reporting Any Fever Post Dose 2 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Any fever = Fever (axillary) ≥ 38°C.
  • Number of Subjects Reporting Any Rash Post Dose 1 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Assessed were any localized or generalized rash, rash with fever, varicella-like rash and measles/rubella-like rash. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any Rash Post Dose 2 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Assessed were any localized or generalized rash, rash with fever, varicella-like rash and measles/rubella-like rash. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Assessed MMR specific solicited general AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Assessed MMR specific solicited general AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any Unsolicited AES Post Dose 1 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Unsolicited AE was defined as any AE reported in reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any Unsolicited AES Post Dose 2 [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ]
    Unsolicited AE was defined as any AE reported in reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects Reporting Any AEs of Specific Interest [ Time Frame: From Day 0 through the end of the study (Day 222) ]
    AEs of specific interest included new onset chronic disease (NOCD) (e.g., autoimmune disorders, asthma, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia and allergies) and AEs prompting emergency room (ER) visits.
  • Number of Subjects Reporting Any Serious Adverse Events (SAEs) [ Time Frame: From Day 0 through the end of the study (Day 222) ]
    SAEs assessed include any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2012)
  • Immunogenicity of the MMR vaccines post-dose 2 (US post-dose 2 sub-cohort) in terms of antibody concentration. [ Time Frame: At Day 84 ]
  • Occurrence of solicited local symptoms. [ Time Frame: Days 0-3 ]
  • Occurrence of solicited general symptoms. [ Time Frame: Days 0-42 ]
  • Occurrence of Unsolicited adverse events. [ Time Frame: Days 0-42 ]
  • Occurrence of Adverse events of specific interest. [ Time Frame: From Day 0 through the end of study (Day 222) ]
  • Serious adverse events (SAEs). [ Time Frame: From Day 0 through the end of study (Day 222) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Children in Their Second Year of Life
Official Title  ICMJE Immunogenicity and Safety Study of GSK Biologicals' Priorix Vaccine (209762) at an End of Shelf-life Potency Compared to Merck & Co., Inc.'s Measles-mumps-rubella (MMR) Vaccine When Both Are Given on a 2-dose Schedule to Healthy Children in Their 2nd Year of Life
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).
Detailed Description This trial is a Phase IIIA, randomized, observer-blind, controlled, multi-center, multi-country study with four parallel groups. This study will evaluate the immunogenicity and safety of GSK Biologicals' trivalent investigational MMR vaccine (referred to as Inv_MMR vaccine, throughout this document) in contrast to the US standard of care comparator vaccine (M-M-R II, Merck and Co., Inc., referred to as Com_MMR throughout this document) in children during their second year of life. The first dose of this two-dose study is designed to establish the end of shelf-life potency of Inv_MMR vaccine. The Inv_MMR vaccine will be given as one of two lots; one of a minimum potency, designated Inv_MMR_Min; and the other at a mid-range or medium potency designated Inv_MMR_Med to two groups. The second dose for both of these Inv_MMR groups will have a potency within the release range of the marketed vaccine. The Com_MMR vaccine will consist of two lots designated Com_MMR_L1 and Com_MMR_L2 and will be analyzed as pooled lots within the study. The first MMR vaccine dose will be co-administered with Varivax, Havrix and (in the US sub-cohort only) Prevnar 13 which are routinely administered to children of this age in the US.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Measles
  • Mumps
  • Rubella
Intervention  ICMJE
  • Biological: Priorix
    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.
    Other Names:
    • GSK Biologicals' live attenuated measles
    • mumps
    • rubella vaccine
  • Biological: M-M-R II
    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.
    Other Names:
    • Merck & Co.
    • Inc.'s measles
    • mumps
    • rubella virus vaccine
    • live
  • Biological: Varivax
    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.
    Other Names:
    • Merck & Co.
    • Inc.'s varicella virus vaccine
    • live
  • Biological: Havrix
    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.
    Other Names:
    • GSK Biologicals' hepatitis A vaccine
    • inactivated
  • Biological: Prevnar 13
    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.
    Other Name: Pfizer Inc.'s pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein)
Study Arms  ICMJE
  • Experimental: Inv_MMR_Min Group
    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.
    Interventions:
    • Biological: Priorix
    • Biological: Varivax
    • Biological: Havrix
    • Biological: Prevnar 13
  • Experimental: Inv_MMR_Med Group
    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.
    Interventions:
    • Biological: Priorix
    • Biological: Varivax
    • Biological: Havrix
    • Biological: Prevnar 13
  • Active Comparator: Com_MMR Group
    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.
    Interventions:
    • Biological: M-M-R II
    • Biological: Varivax
    • Biological: Havrix
    • Biological: Prevnar 13
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 19, 2018)
4538
Original Estimated Enrollment  ICMJE
 (submitted: September 6, 2012)
4500
Actual Study Completion Date  ICMJE August 18, 2015
Actual Primary Completion Date February 3, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Acute disease at the time of enrollment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Fever is defined as temperature ≥38°C/100.4°F by any age appropriate route. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever.
  • Active untreated tuberculosis based on medical history.
  • Any other condition which, in the opinion of the Investigator, prevents the child from participating in the study.

For US children only:

• A child that previously received a fourth dose of any pneumococcal conjugate vaccine.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 15 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Finland,   Malaysia,   Puerto Rico,   Spain,   Thailand,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01681992
Other Study ID Numbers  ICMJE 115649
2011-004905-26 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP