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Evaluation of Immunogenicity and Safety of VARIVAX® Passage Extension 34 (PE34) Process in Children (V210-A03)

Phase 3
Completed
Conditions
Varicella
Interventions
Biological: VARIVAX® 2016 Commercial Process
Biological: VARIVAX® PE34 Process
Biological: M-M-R II®
Registration Number
NCT03239873
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

This study will evaluate the immunogenicity, safety, and tolerability of VARIVAX® (Varicella Virus Vaccine Live) manufactured with a new passage extension (PE34) process compared with the VARIVAX® 2016 commercial process. The primary hypotheses being tested are that antibody response rate and mean antibody titer induced at 6 weeks after a single vaccination by VARIVAX® PE34 Process are non-inferior to those induced by VARIVAX® 2016 commercial process, and that antibody response rate induced by VARIVAX® PE34 Process is acceptable.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
600
Inclusion Criteria
  • Negative clinical history for varicella, herpes zoster, measles, mumps, and rubella
Exclusion Criteria
  • Received any measles, mumps, rubella, or varicella vaccine at any time prior to the study, or is anticipated to receive any of these vaccines outside the study
  • Any congenital or acquired immune deficiency, neoplastic disease, or depressed immunity
  • Received systemic immunomodulatory steroids within 3 months prior to entering the study or is expected to receive them during the course of the study
  • History of allergy or anaphylactic reaction to neomycin, gelatin, sorbitol, egg proteins, chicken proteins, or any component of VARIVAX® or M-M-R II®
  • Has any blood dyscrasias, leukemia, lymphoma, or other malignant neoplasm affecting the bone marrow or lymphatic systems
  • Received salicylates within 14 days prior to study vaccination
  • Exposed to varicella, herpes zoster, measles, mumps, or rubella in the 4 weeks prior to study vaccination
  • Received immune globulin, a blood transfusion, or blood-derived products within 5 months prior to study vaccination
  • History of seizure disorder, including febrile seizure
  • Fever illness (>=102.2 °F [39.0 °C] within 72 hours prior to study vaccination
  • History of thrombocytopenia
  • Born to a human immunodeficiency virus (HIV)-infected mother
  • Has a diagnosis of active untreated tuberculosis
  • Participated in any other clinical trial (other than a surveillance study) within 30 days prior to study enrollment.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VARIVAX® PE34 Process + Measles, Mumps, Rubella (M-M-R) II®M-M-R II®VARIVAX® Passage Extension (PE34) Process vaccine 0.5 mL administered in the left arm or thigh and M-M-R II® vaccine 0.5 mL administered in the right arm or thigh by subcutaneous injection on Day 1 and Day 91
VARIVAX® 2016 Commercial Process + M-M-R II®VARIVAX® 2016 Commercial ProcessVARIVAX® 2016 Commercial Process vaccine 0.5 mL administered in the left arm or thigh and M-M-R II® vaccine 0.5 mL administered in the right arm or thigh by subcutaneous injection on Day 1 and Day 91
VARIVAX® PE34 Process + Measles, Mumps, Rubella (M-M-R) II®VARIVAX® PE34 ProcessVARIVAX® Passage Extension (PE34) Process vaccine 0.5 mL administered in the left arm or thigh and M-M-R II® vaccine 0.5 mL administered in the right arm or thigh by subcutaneous injection on Day 1 and Day 91
VARIVAX® 2016 Commercial Process + M-M-R II®M-M-R II®VARIVAX® 2016 Commercial Process vaccine 0.5 mL administered in the left arm or thigh and M-M-R II® vaccine 0.5 mL administered in the right arm or thigh by subcutaneous injection on Day 1 and Day 91
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Varicella Zoster Virus Antibody Levels ≥5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL6 weeks (43 days) after vaccination 1

The varicella zoster virus (VZV) antibody response rate was defined as the percentage of participants with VZV antibody titer ≥5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL among participants who were seronegative to VZV (titers \<1.25 gpELISA units/mL) at baseline.

Geometric Mean Titer of VZV Antibodies6 weeks (43 days) after vaccination 1

The geometric mean titer (GMT) of VZV antibodies after vaccination 1 was assessed. Antibody titers were measured with gpELISA.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%)Up to 42 days after vaccination 1

The percentage of participants with measles-like, rubella-like, varicella-like, zoster-like rash, and mumps-like symptoms after vaccination 1 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.

Percentage of Participants With Immunogenicity to Varicella Zoster Virus in Participants Initially Seropositive to Varicella Zoster Virus Antibody (≥ 5gpELISA Units/mL)6 weeks (~43 days) after vaccination 1

The percentage of participants with seropositive antibody titer (≥1.25gpELISA units/mL) at baseline and postvaccination serology contributing to the per-protocol analysis was assessed. Confidence interval is calculated if there are at least 5 subjects who are seropositive. Antibody titers were assessed using gpELISA.

Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%)Up to 42 days after vaccination 2

The percentage of participants with measles-like, rubella-like, varicella-like, zoster-like rash, and mumps-like symptoms after vaccination 2 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.

Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness After Vaccination 2Up to 5 days after vaccination 2

The percentage of participants with solicited (Vaccine Report Card) injection-site erythema, injection-site swelling, and injection-site pain/tenderness was assessed.

Percentage of Participants With a ≥4-fold Rise From Baseline in Varicella Zoster Virus Antibody Titers in Participants Initially Seropositive to Varicella Zoster Virus AntibodyBaseline and 6 weeks (~43 days) after vaccination 1

The percentage of participants with a geometric mean ≥4-fold rise from baseline of ≥1.25gpELISA units/mL in VZV antibody titer at approximately 43 days after vaccination 1 was assessed.

Percentage of Participants Who Discontinued From the Study Due to an Adverse EventUp to 42 days after vaccination 1 and up to 42 days after vaccination 2

The percentage of participants discontinued from the study due to an adverse event for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.

Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 1 (Incidence > 0%)Up to 42 days after vaccination 1

The percentage of participants with unsolicited injection-site adverse events (or AEs not superficially listed on eVRC) for Day 1 through Day 42 after vaccination 1 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.

Percentage of Participants With One or More Systemic Adverse Events After Vaccination 2 (Incidence > 0)Up to 42 days after vaccination 2

All systemic adverse events were recorded on an electronic vaccination report card (eVRC) for Day 1 through Day 42 after vaccination 2. The percentage of participants with one or more systemic adverse events was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.

Percentage of Participants With One or More Vaccine-Related Serious Adverse EventsUp to ~180 days after vaccination 2

The percentage of participants with one or more vaccine-related serious adverse events up to \~180 days after vaccination 2 was reported. The study investigator determines whether the serious adverse event is related to the vaccine.

Percentage of Participants With Medically-Attended Adverse Events (Incidence ≥5%)Up to ~180 days after vaccination 2 (Up to ~285 days)

The percentage of participants with medically-attended AEs up to \~180 days after vaccination 2 that did not meet the definition of serious adverse event (incidence ≥5% in one or more vaccination groups) was reported.

Percentage of Participants With Fever (≥102.2 °F Oral Equivalent)Up to 42 days after vaccination 1; Up to 42 days after vaccination 2

The percentage of participants with fever ≥102.2 °F oral equivalent for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.

Percentage of Participants With One or More Adverse EventsUp to 42 days after vaccination 1 and up to 42 days after vaccination 2

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with one or more adverse events for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.

Percentage of Participants With One or More Vaccine-Related Adverse EventsUp to 42 days after vaccination 1 and up to 42 days after vaccination 2

The percentage of participants with one or more vaccine-related adverse events for Day 1 through Day 42 after vaccination 1 and Day 1 through Day 42 after vaccination 2 was reported.

Percentage of Participants With One or More Systemic Adverse Events After Vaccination 1 (Incidence ≥ 4)Up to 42 days after vaccination 1

All systemic adverse events were recorded on an electronic vaccination report card (eVRC) for Day 1 through Day 42 after vaccination 1. The percentage of participants with one or more systemic adverse events (incidence ≥4 participants in one or more of the vaccination groups) was reported.

Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness After Vaccination 1Up to 5 days after vaccination 1

The percentage of participants with solicited (on a Vaccine Report Card) injection-site erythema, injection-site swelling, or injection-site pain/tenderness was assessed.

Percentage of Participants With One or More Serious Adverse EventsUp to ~180 days after vaccination 2 (Up to ~285 days)

A serious adverse event (SAE) is defined as an adverse event that resulted in death, was life threatening, resulted in persistent or significant disability or incapacity, resulted in or prolonged a hospitalization, is a congenital anomaly or birth defect, is a cancer, was an overdose, or was an important medical event based on appropriate medical judgment. The percentage of participants with one or more SAEs \~180 days after vaccination 2 was reported.

Geometric Mean Fold Rise From Baseline in Varicella Zoster Virus Antibody Titer in Participants Initially Seropositive to Varicella Zoster Virus AntibodyBaseline and 6 weeks (~43 days) after vaccination 1

Blood samples were taken at pre-vaccination (baseline) and approximately 43 days after vaccination 1 to determine the geometric mean titer (GMT) of VZV antibodies via gpELISA. The geometric mean fold rise (GMFR) was calculated as GMT post vaccination 1/GMT pre-vaccination (baseline). Confidence interval is calculated if there are at least 5 subjects who are seropositive.

Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 2 (Incidence > 0%)Up to 42 days after vaccination 2

The percentage of participants with unsolicited injection-site adverse events (or AEs not superficially listed on eVRC) for Day 1 through Day 42 after vaccination 2 was assessed. A specific adverse event was reported only if its incidence was \>0% in one or more vaccination groups after rounding.

Trial Locations

Locations (37)

Tanner Clinic ( Site 0010)

🇺🇸

Layton, Utah, United States

Wee Care Pediatrics-Roy ( Site 0043)

🇺🇸

Roy, Utah, United States

Premier Health Research Center, LLC ( Site 0044)

🇺🇸

Downey, California, United States

Children's Research at Altamonte Pediatric Associates ( Site 0040)

🇺🇸

Lake Mary, Florida, United States

IMMUNOe Research Centers ( Site 0046)

🇺🇸

Thornton, Colorado, United States

Advanced Clinical Research ( Site 0038)

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Meridian, Idaho, United States

Heartland Research Associates, LLC ( Site 0029)

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Augusta, Kansas, United States

Heartland Research Associates, LLC ( Site 0015)

🇺🇸

Newton, Kansas, United States

Cotton O'Neil Research Center ( Site 0014)

🇺🇸

Topeka, Kansas, United States

The Center For Pharmaceutical Research PC ( Site 0011)

🇺🇸

Kansas City, Missouri, United States

ACC Pediatric Research ( Site 0041)

🇺🇸

Haughton, Louisiana, United States

Ohio Pediatric Research Association ( Site 0035)

🇺🇸

Dayton, Ohio, United States

Blue Ridge Pediatric & Adolescent Medicine ( Site 0001)

🇺🇸

Boone, North Carolina, United States

Kid's Way Pediatrics ( Site 0047)

🇺🇸

Hermitage, Pennsylvania, United States

Palmetto Pediatrics, PA ( Site 0023)

🇺🇸

Charleston, South Carolina, United States

Coastal Pediatric Research ( Site 0006)

🇺🇸

Charleston, South Carolina, United States

Benchmark Research ( Site 0005)

🇺🇸

Austin, Texas, United States

J Lewis Research Inc/Jordan River Family Medicine ( Site 0019)

🇺🇸

South Jordan, Utah, United States

Wee Care Pediatrics ( Site 0036)

🇺🇸

Syracuse, Utah, United States

Pediatric Research of Charlottesville, LLC ( Site 0039)

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Charlottesville, Virginia, United States

Children's Clinic of Jonesboro, PA ( Site 0030)

🇺🇸

Jonesboro, Arkansas, United States

Southland Clinical Research Center ( Site 0017)

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Anaheim, California, United States

Senders Pediatrics ( Site 0034)

🇺🇸

Cleveland, Ohio, United States

Pediatric Healthcare of Northwest Houston ( Site 0027)

🇺🇸

Tomball, Texas, United States

Kentucky Pediatric/Adult Research Inc ( Site 0012)

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Bardstown, Kentucky, United States

Child Health Care Associates ( Site 0045)

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East Syracuse, New York, United States

Holston Medical Group Pediatrics ( Site 0024)

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Kingsport, Tennessee, United States

University of Texas Medical Branch at Galveston ( Site 0032)

🇺🇸

Galveston, Texas, United States

West Houston Clinical Research Services ( Site 0009)

🇺🇸

Houston, Texas, United States

Advanced Clinical Research ( Site 0020)

🇺🇸

West Jordan, Utah, United States

Alabama Clinical Therapeutics ( Site 0018)

🇺🇸

Birmingham, Alabama, United States

California Research Foundation ( Site 0003)

🇺🇸

San Diego, California, United States

University of South Florida ( Site 0042)

🇺🇸

Tampa, Florida, United States

University of Louisville: Pediatric Clinical Trials Unit ( Site 0025)

🇺🇸

Louisville, Kentucky, United States

Ford, Simpson, Lively & Rice Pediatrics, PLLC ( Site 0037)

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Winston-Salem, North Carolina, United States

J Lewis Research Inc / Foothill Family Clinic ( Site 0016)

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Salt Lake City, Utah, United States

J Lewis Research Inc/Foothill Family Clinic South ( Site 0004)

🇺🇸

Salt Lake City, Utah, United States

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