ProQuad® Intramuscular vs Subcutaneous

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Measles, Mumps, Rubella, Varicella

Intervention / Treatment
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* Biological: ProQuad®


Participation Criteria
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Eligibility Criteria
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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,

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intramuscular ProQuad®<br>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. | Biological: ProQuad®<br>* 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.<br>|
| Active Comparator: Subcutaneous ProQuad®<br>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. | Biological: ProQuad®<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 10 (6 weeks after Dose 2 on Week 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 4 | 
| 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. | Week 4 | 
| 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. | Week 4 | 
| 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. | Week 4 | 
| 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. | Week 4 | 
| 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. | Week 10 (6 weeks after Dose 2 on Week 4) | 
| 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. | Week 10 (6 weeks after Dose 2 on Week 4) | 
| 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. | Week 10 (6 weeks after Dose 2 on Week 4) | 
| 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. | Week 10 (6 weeks after Dose 2 on Week 4) | 
| 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. | From Day 0 up to Day 28 (up to 28 days after the first ProQuad® dose) | 
| 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. | From Day 30 up to Day 58 (up to 28 days after the second ProQuad® dose) | 
| 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. | From Day 0 up to Day 28 (up to 28 days after the first ProQuad® dose) |