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

Varicella Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03239873
• Other study ID #: V210-A03
• Secondary ID: V210-A032017-001
• Status: Completed
• Phase: Phase 3
• Start date: October 17, 2017
• Est. completion date: April 2, 2019

Study information

• Verified date: January 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: April 2, 2019
• Est. primary completion date: August 14, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 23 Months

Eligibility

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.

Related Conditions & MeSH terms

• Chickenpox
• Varicella

Intervention

Biological:
• VARIVAX® PE34 Process
Varicella virus vaccine live manufactured with a new passage extension process (PE34)
• VARIVAX® 2016 Commercial Process
Varicella virus vaccine live manufactured with the 2016 commercial process
• M-M-R II®
Measles, Mumps, and Rubella virus vaccine live

Locations

Country	Name	City	State
United States	Southland Clinical Research Center ( Site 0017)	Anaheim	California
United States	Heartland Research Associates, LLC ( Site 0029)	Augusta	Kansas
United States	Benchmark Research ( Site 0005)	Austin	Texas
United States	Kentucky Pediatric/Adult Research Inc ( Site 0012)	Bardstown	Kentucky
United States	Alabama Clinical Therapeutics ( Site 0018)	Birmingham	Alabama
United States	Blue Ridge Pediatric & Adolescent Medicine ( Site 0001)	Boone	North Carolina
United States	Coastal Pediatric Research ( Site 0006)	Charleston	South Carolina
United States	Palmetto Pediatrics, PA ( Site 0023)	Charleston	South Carolina
United States	Pediatric Research of Charlottesville, LLC ( Site 0039)	Charlottesville	Virginia
United States	Senders Pediatrics ( Site 0034)	Cleveland	Ohio
United States	Ohio Pediatric Research Association ( Site 0035)	Dayton	Ohio
United States	Premier Health Research Center, LLC ( Site 0044)	Downey	California
United States	Child Health Care Associates ( Site 0045)	East Syracuse	New York
United States	University of Texas Medical Branch at Galveston ( Site 0032)	Galveston	Texas
United States	ACC Pediatric Research ( Site 0041)	Haughton	Louisiana
United States	Kid's Way Pediatrics ( Site 0047)	Hermitage	Pennsylvania
United States	West Houston Clinical Research Services ( Site 0009)	Houston	Texas
United States	Children's Clinic of Jonesboro, PA ( Site 0030)	Jonesboro	Arkansas
United States	The Center For Pharmaceutical Research PC ( Site 0011)	Kansas City	Missouri
United States	Holston Medical Group Pediatrics ( Site 0024)	Kingsport	Tennessee
United States	Children's Research at Altamonte Pediatric Associates ( Site 0040)	Lake Mary	Florida
United States	Tanner Clinic ( Site 0010)	Layton	Utah
United States	University of Louisville: Pediatric Clinical Trials Unit ( Site 0025)	Louisville	Kentucky
United States	Advanced Clinical Research ( Site 0038)	Meridian	Idaho
United States	Heartland Research Associates, LLC ( Site 0015)	Newton	Kansas
United States	Wee Care Pediatrics-Roy ( Site 0043)	Roy	Utah
United States	J Lewis Research Inc / Foothill Family Clinic ( Site 0016)	Salt Lake City	Utah
United States	J Lewis Research Inc/Foothill Family Clinic South ( Site 0004)	Salt Lake City	Utah
United States	California Research Foundation ( Site 0003)	San Diego	California
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	University of South Florida ( Site 0042)	Tampa	Florida
United States	IMMUNOe Research Centers ( Site 0046)	Thornton	Colorado
United States	Pediatric Healthcare of Northwest Houston ( Site 0027)	Tomball	Texas
United States	Cotton O'Neil Research Center ( Site 0014)	Topeka	Kansas
United States	Advanced Clinical Research ( Site 0020)	West Jordan	Utah
United States	Ford, Simpson, Lively & Rice Pediatrics, PLLC ( Site 0037)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 administere — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)