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

A Phase 3, Double-Blind, Randomized, Multicenter, Controlled Study to Evaluate the Immunogenicity, Safety, and Tolerability of VARIVAX™ Passage Extension 34 (PE34) Process Administered Concomitantly With M-M-R™ II

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.

Study Overview

• Status: Completed
• Conditions: Varicella
• Intervention / Treatment: Biological: VARIVAX® PE34 Process; Biological: M-M-R II®; Biological: VARIVAX® 2016 Commercial Process

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Alabama Clinical Therapeutics ( Site 0018)
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Children's Clinic of Jonesboro, PA ( Site 0030)
  • California
    • Anaheim, California, United States, 92804
      • Southland Clinical Research Center ( Site 0017)
    • Downey, California, United States, 90240
      • Premier Health Research Center, LLC ( Site 0044)
    • San Diego, California, United States, 92123
      • California Research Foundation ( Site 0003)
  • Colorado
    • Thornton, Colorado, United States, 80233
      • IMMUNOe Research Centers ( Site 0046)
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Children's Research at Altamonte Pediatric Associates ( Site 0040)
    • Tampa, Florida, United States, 33606
      • University of South Florida ( Site 0042)
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research ( Site 0038)
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Heartland Research Associates, LLC ( Site 0029)
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates, LLC ( Site 0015)
    • Topeka, Kansas, United States, 66604
      • Cotton O'Neil Research Center ( Site 0014)
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/Adult Research Inc ( Site 0012)
    • Louisville, Kentucky, United States, 40202
      • University of Louisville: Pediatric Clinical Trials Unit ( Site 0025)
  • Louisiana
    • Haughton, Louisiana, United States, 71037
      • ACC Pediatric Research ( Site 0041)
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center For Pharmaceutical Research PC ( Site 0011)
  • New York
    • East Syracuse, New York, United States, 13057
      • Child Health Care Associates ( Site 0045)
  • North Carolina
    • Boone, North Carolina, United States, 28607
      • Blue Ridge Pediatric & Adolescent Medicine ( Site 0001)
    • Winston-Salem, North Carolina, United States, 27103
      • Ford, Simpson, Lively & Rice Pediatrics, PLLC ( Site 0037)
  • Ohio
    • Cleveland, Ohio, United States, 44121
      • Senders Pediatrics ( Site 0034)
    • Dayton, Ohio, United States, 45414
      • Ohio Pediatric Research Association ( Site 0035)
  • Pennsylvania
    • Hermitage, Pennsylvania, United States, 16148
      • Kid's Way Pediatrics ( Site 0047)
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research ( Site 0006)
    • Charleston, South Carolina, United States, 29406
      • Palmetto Pediatrics, PA ( Site 0023)
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group Pediatrics ( Site 0024)
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research ( Site 0005)
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston ( Site 0032)
    • Houston, Texas, United States, 77055
      • West Houston Clinical Research Services ( Site 0009)
    • Tomball, Texas, United States, 77375
      • Pediatric Healthcare of Northwest Houston ( Site 0027)
  • Utah
    • Layton, Utah, United States, 84041
      • Tanner Clinic ( Site 0010)
    • Roy, Utah, United States, 84067
      • Wee Care Pediatrics-Roy ( Site 0043)
    • Salt Lake City, Utah, United States, 84109
      • J Lewis Research Inc / Foothill Family Clinic ( Site 0016)
    • Salt Lake City, Utah, United States, 84121
      • J Lewis Research Inc/Foothill Family Clinic South ( Site 0004)
    • South Jordan, Utah, United States, 84095
      • J Lewis Research Inc/Jordan River Family Medicine ( Site 0019)
    • Syracuse, Utah, United States, 84075
      • Wee Care Pediatrics ( Site 0036)
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research ( Site 0020)
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Pediatric Research of Charlottesville, LLC ( Site 0039)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VARIVAX® PE34 Process + Measles, Mumps, Rubella (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	Biological: VARIVAX® PE34 Process; Varicella virus vaccine live manufactured with a new passage extension process (PE34); Biological: M-M-R II®; Measles, Mumps, and Rubella virus vaccine live
Active Comparator: VARIVAX® 2016 Commercial Process + 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	Biological: M-M-R II®; Measles, Mumps, and Rubella virus vaccine live; Biological: VARIVAX® 2016 Commercial Process; Varicella virus vaccine live manufactured with the 2016 commercial process

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Varicella Zoster Virus Antibody Levels ≥5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL	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.	6 weeks (43 days) after vaccination 1
Geometric Mean Titer of VZV Antibodies	The geometric mean titer (GMT) of VZV antibodies after vaccination 1 was assessed. Antibody titers were measured with gpELISA.	6 weeks (43 days) after vaccination 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Fever (≥102.2 °F Oral Equivalent)	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.	Up to 42 days after vaccination 1; Up to 42 days after vaccination 2
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 1 (Incidence > 0%)	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.	Up to 42 days after vaccination 1
Percentage of Participants With Systemic Measles-like, Rubella-like, Varicella-like, Zoster-like Rash, and Mumps-like Symptoms After Vaccination 2 (Incidence > 0%)	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.	Up to 42 days after vaccination 2
Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, or Injection-site Pain/Tenderness 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.	Up to 5 days after vaccination 1
Percentage of Participants With Solicited Injection-site Erythema, Injection-site Swelling, and Injection-site Pain/Tenderness 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.	Up to 5 days after vaccination 2
Percentage of Participants With One or More Adverse Events	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.	Up to 42 days after vaccination 1 and up to 42 days after vaccination 2
Percentage of Participants With One or More Serious Adverse Events	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.	Up to ~180 days after vaccination 2 (Up to ~285 days)
Percentage of Participants With One or More Vaccine-Related Adverse Events	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.	Up to 42 days after vaccination 1 and up to 42 days after vaccination 2
Percentage of Participants With One or More Systemic Adverse Events After Vaccination 1 (Incidence ≥ 4)	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.	Up to 42 days after vaccination 1
Percentage of Participants With One or More Systemic Adverse Events After Vaccination 2 (Incidence > 0)	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.	Up to 42 days after vaccination 2
Percentage of Participants With Immunogenicity to Varicella Zoster Virus in Participants Initially Seropositive to Varicella Zoster Virus Antibody (≥ 5gpELISA Units/mL)	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.	6 weeks (~43 days) after vaccination 1
Geometric Mean Fold Rise From Baseline in Varicella Zoster Virus Antibody Titer in Participants Initially Seropositive to Varicella Zoster Virus Antibody	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.	Baseline and 6 weeks (~43 days) after vaccination 1
Percentage of Participants With a ≥4-fold Rise From Baseline in Varicella Zoster Virus Antibody Titers in Participants Initially Seropositive to Varicella Zoster Virus Antibody	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.	Baseline and 6 weeks (~43 days) after vaccination 1
Percentage of Participants With One or More Vaccine-Related Serious Adverse Events	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.	Up to ~180 days after vaccination 2
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event	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.	Up to 42 days after vaccination 1 and up to 42 days after vaccination 2
Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 1 (Incidence > 0%)	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.	Up to 42 days after vaccination 1
Percentage of Participants With One or More Unsolicited Injection-Site Adverse Events After Vaccination 2 (Incidence > 0%)	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.	Up to 42 days after vaccination 2
Percentage of Participants With Medically-Attended Adverse Events (Incidence ≥5%)	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.	Up to ~180 days after vaccination 2 (Up to ~285 days)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Silas PE, Zissman EN, Gardner J, Helian S, Lee AW, Platt HL. A double-blind, randomized, multicenter, controlled study to evaluate the immunogenicity, safety, and tolerability of varicella vaccine (VARIVAX) passage extension 34 (PE34) process administered concomitantly with measles, mumps, and rubella vaccine (M-M-R II). Hum Vaccin Immunother. 2020 Nov 1;16(11):2634-2640. doi: 10.1080/21645515.2020.1743122. Epub 2020 May 19.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): August 14, 2018
• Study Completion (Actual): April 2, 2019

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 4, 2017

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Chickenpox
• Other Study ID Numbers: V210-A03 (Other Identifier: Merck); 2017-001910-27 (Other Identifier: EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No