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ProQuad® Intramuscular vs Subcutaneous

Primary Purpose

Measles, Mumps, Rubella

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ProQuad®
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Measles

Eligibility Criteria

12 Months - 18 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy participant of either gender,
  • Age 12 to 18 months,
  • Negative clinical history of measles, mumps, rubella, varicella and zoster,
  • Consent form signed by both holders of the parental authority or by the legal representative
  • Holder(s) of the the parental authority / 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
  • Any recent (≤3 days) history of febrile illness
  • Any severe chronic disease,
  • Active untreated tuberculosis,
  • Known personal history of seizure disorder,
  • Any known blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic systems,
  • Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection,
  • Any immune impairment or humoral/cellular deficiency, neoplastic disease or depressed immunity including those resulting from corticosteroid [any long-term (≥14 days) administration of systemic corticosteroid therapy given daily or on alternate days at high doses (≥2 mg/kg/day prednisone equivalent or ≥20 mg/day if weight more than 10 kg) within the previous 30 days] or other immunosuppressive therapy,
  • Any previous (≤ 150 days) receipt of immune globulin or any blood-derived product or scheduled to be administered through Visit 3,
  • Any recent (≤7 days) tuberculin test or scheduled tuberculin test through Visit 3,
  • Any recent (≤30 days) receipt of an inactivated or a live vaccine or scheduled vaccination through Visit 3,

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Intramuscular ProQuad®

    Subcutaneous ProQuad®

    Arm Description

    Participants will receive doses of ProQuad® by IM injection on Day 1 and Day 30 into the deltoid muscle perpendicular to the skin, with the first dose in the right arm and the second dose in the left arm.

    Participants will receive doses of ProQuad® by SC injection on Day 1 and Day 30 in the deltoid area at a 45° angle to the skin, with the first dose in the right arm and second dose in the left arm.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Meeting Antibody Response Rate Criteria Six Weeks After Completing ProQuad® Treatment
    Antibody response rates were determined 6 weeks after the second dose of IM or SC ProQuad®. 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). Response rates were determined 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.

    Secondary Outcome Measures

    Percentage of Participants Meeting Antibody Response Rate Criteria Four Weeks After the First ProQuad® Dose
    Antibody response rates were determined 4 weeks after the first dose of IM or SC ProQuad®. Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. Response rates were determined 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.
    Antibody Geometric Mean Titres (GMT) to Measles Four Weeks After the First ProQuad® Dose
    Antibody titre levels to measles were determined 4 weeks after the first dose of IM or SC ProQuad®. Measles antibody levels were determined using ELISA. Titre levels were determined in participants with baseline measles titre <255 mIU/mL.
    Antibody GMT to Mumps Four Weeks After the First ProQuad® Dose
    Antibody titre levels to mumps were determined 4 weeks after the first dose of IM or SC ProQuad®. Mumps antibody levels were determined using ELISA. Titre levels were determined in participants with baseline mumps titres <10 ELISA Ab units mL.
    Antibody GMT to Rubella Four Weeks After the First ProQuad® Dose
    Antibody titre levels to rubella were determined 4 weeks after the first dose of IM or SC ProQuad®. Rubella antibody levels were determined using ELISA. Titre levels were determined in participants with baseline rubella titre <10 IU/mL.
    Antibody GMT to Varicella Four Weeks After the First ProQuad® Dose
    Antibody titre levels to varicella were determined 4 weeks after the first dose of IM or SC ProQuad®. Varicella antibody levels were determined with gpELISA. Titre levels were determined in participants with baseline varicella antibody titre <1.25 gpELISA units/mL.
    Antibody GMT to Measles Six Weeks After Completing ProQuad® Treatment
    Antibody titre levels to measles were determined 6 weeks after the second dose of IM or SC ProQuad®. Measles antibody levels were determined using ELISA. Titre levels were determined in participants with baseline measles titre <255 mIU/mL.
    Antibody GMT to Mumps Six Weeks After Completing ProQuad® Treatment
    Antibody titre levels to mumps were determined 6 weeks after the second dose of IM or SC ProQuad®. Mumps antibody levels were determined using ELISA. Titre levels were determined in participants with baseline mumps titre <10 ELISA Ab units mL.
    Antibody GMT to Rubella Six Weeks After Completing ProQuad® Treatment
    Antibody titre levels to rubella were determined 6 weeks after the second dose of IM or SC ProQuad®. Rubella antibody levels were determined using ELISA. Titre levels were determined in participants with baseline rubella titre <10 IU/mL.
    Antibody GMT to Varicella Six Weeks After Completing ProQuad® Treatment
    Antibody titre levels to varicella were determined 6 weeks after the second dose of IM or SC ProQuad®. Varicella antibody levels were determined with gpELISA. Titre levels were determined in participants with baseline varicella antibody titre <1.25 gpELISA units/mL.
    Percentage of Participants Experiencing an Injection-site Adverse Event (AE) or Vaccine-related Systemic AE After the First ProQuad® Dose
    An AE is any untoward medical occurrence in a participant administered an investigational medicinal product (IMP) and which does not necessarily have a causal relationship with the IMP. Injection-site AEs (e.g., erythema, swelling, pain) and systemic vaccine-related AEs (e.g., pyrexia) were AEs of interest.
    Percentage of Participants Experiencing an Injection-site AE or Vaccine-related Systemic AE After the Second ProQuad® Dose
    An AE is any untoward medical occurrence in a participant administered an IMP and which does not necessarily have a causal relationship with the IMP. Injection-site AEs (e.g., erythema, swelling, pain) and systemic vaccine-related AEs (e.g., pyrexia) were AEs of interest.
    Percentage of Participants Discontinuing From Study Therapy Due to an AE After the First ProQuad® Dose
    An AE is any untoward medical occurrence in a participant administered an IMP and which does not necessarily have a causal relationship with the IMP.

    Full Information

    First Posted
    November 21, 2006
    Last Updated
    August 10, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00402831
    Brief Title
    ProQuad® Intramuscular vs Subcutaneous
    Official Title
    An Open, Randomised, Comparative, Multicentre Study of the Immunogenicity and Safety of ProQuad® When Administered by Intramuscular (IM) Route or Subcutaneous (SC) Route to Healthy Children Aged 12 to 18 Months
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    October 6, 2006 (Actual)
    Primary Completion Date
    May 11, 2007 (Actual)
    Study Completion Date
    May 11, 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Primary objective: To demonstrate that two doses of ProQuad® administered by IM route are as immunogenic as two doses of ProQuad® administered by SC route to healthy children 12 to 18 months of age in terms of antibody response rates to measles, mumps, rubella and to varicella at 42 days following the second dose of ProQuad® Secondary objectives: To describe the antibody response rates to measles, mumps, rubella and varicella measured 30 days following the first dose of ProQuad® administered by IM or SC route, To describe the antibody titres to measles, mumps, rubella and varicella at 30 days following the first dose and at 42 days following the second dose of ProQuad® both administered by IM or SC route, To describe the safety profile of two doses of ProQuad® both administered by IM or SC route.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Measles, Mumps, Rubella, Varicella

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    405 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Intramuscular ProQuad®
    Arm Type
    Experimental
    Arm Description
    Participants will receive doses of ProQuad® by IM injection on Day 1 and Day 30 into the deltoid muscle perpendicular to the skin, with the first dose in the right arm and the second dose in the left arm.
    Arm Title
    Subcutaneous ProQuad®
    Arm Type
    Active Comparator
    Arm Description
    Participants will receive doses of ProQuad® by SC injection on Day 1 and Day 30 in the deltoid area at a 45° angle to the skin, with the first dose in the right arm and second dose in the left arm.
    Intervention Type
    Biological
    Intervention Name(s)
    ProQuad®
    Intervention Description
    Each dose (0.5 mL) contains live attenuated versions of measles virus Enders' Edmonston strain, mumps virus Jeryl Lynn™ (Level B) strain, rubella virus Wistar RA 27/3 strain, and varicella virus Oka/Merck strain.
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Meeting Antibody Response Rate Criteria Six Weeks After Completing ProQuad® Treatment
    Description
    Antibody response rates were determined 6 weeks after the second dose of IM or SC ProQuad®. 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). Response rates were determined 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.
    Time Frame
    Week 10 (6 weeks after Dose 2 on Week 4)
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Meeting Antibody Response Rate Criteria Four Weeks After the First ProQuad® Dose
    Description
    Antibody response rates were determined 4 weeks after the first dose of IM or SC ProQuad®. Measles, mumps and rubella antibody levels were determined using ELISA and varicella antibody levels were determined with gpELISA. Response rates were determined 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.
    Time Frame
    Week 4
    Title
    Antibody Geometric Mean Titres (GMT) to Measles Four Weeks After the First ProQuad® Dose
    Description
    Antibody titre levels to measles were determined 4 weeks after the first dose of IM or SC ProQuad®. Measles antibody levels were determined using ELISA. Titre levels were determined in participants with baseline measles titre <255 mIU/mL.
    Time Frame
    Week 4
    Title
    Antibody GMT to Mumps Four Weeks After the First ProQuad® Dose
    Description
    Antibody titre levels to mumps were determined 4 weeks after the first dose of IM or SC ProQuad®. Mumps antibody levels were determined using ELISA. Titre levels were determined in participants with baseline mumps titres <10 ELISA Ab units mL.
    Time Frame
    Week 4
    Title
    Antibody GMT to Rubella Four Weeks After the First ProQuad® Dose
    Description
    Antibody titre levels to rubella were determined 4 weeks after the first dose of IM or SC ProQuad®. Rubella antibody levels were determined using ELISA. Titre levels were determined in participants with baseline rubella titre <10 IU/mL.
    Time Frame
    Week 4
    Title
    Antibody GMT to Varicella Four Weeks After the First ProQuad® Dose
    Description
    Antibody titre levels to varicella were determined 4 weeks after the first dose of IM or SC ProQuad®. Varicella antibody levels were determined with gpELISA. Titre levels were determined in participants with baseline varicella antibody titre <1.25 gpELISA units/mL.
    Time Frame
    Week 4
    Title
    Antibody GMT to Measles Six Weeks After Completing ProQuad® Treatment
    Description
    Antibody titre levels to measles were determined 6 weeks after the second dose of IM or SC ProQuad®. Measles antibody levels were determined using ELISA. Titre levels were determined in participants with baseline measles titre <255 mIU/mL.
    Time Frame
    Week 10 (6 weeks after Dose 2 on Week 4)
    Title
    Antibody GMT to Mumps Six Weeks After Completing ProQuad® Treatment
    Description
    Antibody titre levels to mumps were determined 6 weeks after the second dose of IM or SC ProQuad®. Mumps antibody levels were determined using ELISA. Titre levels were determined in participants with baseline mumps titre <10 ELISA Ab units mL.
    Time Frame
    Week 10 (6 weeks after Dose 2 on Week 4)
    Title
    Antibody GMT to Rubella Six Weeks After Completing ProQuad® Treatment
    Description
    Antibody titre levels to rubella were determined 6 weeks after the second dose of IM or SC ProQuad®. Rubella antibody levels were determined using ELISA. Titre levels were determined in participants with baseline rubella titre <10 IU/mL.
    Time Frame
    Week 10 (6 weeks after Dose 2 on Week 4)
    Title
    Antibody GMT to Varicella Six Weeks After Completing ProQuad® Treatment
    Description
    Antibody titre levels to varicella were determined 6 weeks after the second dose of IM or SC ProQuad®. Varicella antibody levels were determined with gpELISA. Titre levels were determined in participants with baseline varicella antibody titre <1.25 gpELISA units/mL.
    Time Frame
    Week 10 (6 weeks after Dose 2 on Week 4)
    Title
    Percentage of Participants Experiencing an Injection-site Adverse Event (AE) or Vaccine-related Systemic AE After the First ProQuad® Dose
    Description
    An AE is any untoward medical occurrence in a participant administered an investigational medicinal product (IMP) and which does not necessarily have a causal relationship with the IMP. Injection-site AEs (e.g., erythema, swelling, pain) and systemic vaccine-related AEs (e.g., pyrexia) were AEs of interest.
    Time Frame
    From Day 0 up to Day 28 (up to 28 days after the first ProQuad® dose)
    Title
    Percentage of Participants Experiencing an Injection-site AE or Vaccine-related Systemic AE After the Second ProQuad® Dose
    Description
    An AE is any untoward medical occurrence in a participant administered an IMP and which does not necessarily have a causal relationship with the IMP. Injection-site AEs (e.g., erythema, swelling, pain) and systemic vaccine-related AEs (e.g., pyrexia) were AEs of interest.
    Time Frame
    From Day 30 up to Day 58 (up to 28 days after the second ProQuad® dose)
    Title
    Percentage of Participants Discontinuing From Study Therapy Due to an AE After the First ProQuad® Dose
    Description
    An AE is any untoward medical occurrence in a participant administered an IMP and which does not necessarily have a causal relationship with the IMP.
    Time Frame
    From Day 0 up to Day 28 (up to 28 days after the first ProQuad® dose)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    12 Months
    Maximum Age & Unit of Time
    18 Months
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Healthy participant of either gender, Age 12 to 18 months, Negative clinical history of measles, mumps, rubella, varicella and zoster, Consent form signed by both holders of the parental authority or by the legal representative Holder(s) of the the parental authority / 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 Any recent (≤3 days) history of febrile illness Any severe chronic disease, Active untreated tuberculosis, Known personal history of seizure disorder, Any known blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic systems, Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection, Any immune impairment or humoral/cellular deficiency, neoplastic disease or depressed immunity including those resulting from corticosteroid [any long-term (≥14 days) administration of systemic corticosteroid therapy given daily or on alternate days at high doses (≥2 mg/kg/day prednisone equivalent or ≥20 mg/day if weight more than 10 kg) within the previous 30 days] or other immunosuppressive therapy, Any previous (≤ 150 days) receipt of immune globulin or any blood-derived product or scheduled to be administered through Visit 3, Any recent (≤7 days) tuberculin test or scheduled tuberculin test through Visit 3, Any recent (≤30 days) receipt of an inactivated or a live vaccine or scheduled vaccination through Visit 3,
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Anne FIQUET, MD
    Organizational Affiliation
    SPMSD
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    30481110
    Citation
    Haas H, Richard P, Eymin C, Fiquet A, Kuter B, Soubeyrand B. Immunogenicity and safety of intramuscular versus subcutaneous administration of a combined measles, mumps, rubella, and varicella vaccine to children 12 to 18 months of age. Hum Vaccin Immunother. 2019;15(4):778-785. doi: 10.1080/21645515.2018.1549452. Epub 2019 Jan 8.
    Results Reference
    derived

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