Evaluation of the Immunogenicity and Safety of VARIVAX™ in Healthy Russians (V210-058)

An Open-Label, Multicenter, Single-arm Study to Evaluate the Immunogenicity of VARIVAX™ in Healthy Russian Individuals 12 Months of Age and Older

The purpose of this study was to evaluate the immunogenicity and safety of VARIVAX™ vaccine in healthy Russian children, adolescents, and adults. No formal hypothesis was tested.

Study Overview

• Status: Completed
• Conditions: Varicella
• Intervention / Treatment: Biological: VARIVAX™

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Kazan, Russian Federation, 420140
    • Republican Clinical Infectious Hospital n.a. A.F. Agafonov ( Site 5816)
  • Saint Petersburg, Russian Federation, 197022
    • Research Institute of Children Infections ( Site 5801)
  • Saint Petersburg, Russian Federation, 197101
    • SPb Pasteur RI of Epidemiology and Microbiology ( Site 5817)
  • Smolensk, Russian Federation, 214019
    • Smolensk State Medical University ( Site 5814)
  • Smolensk, Russian Federation, 214019
    • Smolensk State Medical University ( Site 5815)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• has a negative clinical history for varicella and herpes zoster
• females of reproductive potential have a negative pregnancy test prior to each study vaccination
• females of reproductive potential remain abstinent or use 2 acceptable methods of birth control during study until 3 months following last study vaccination
• females not of reproductive potential do not require a pregnancy test or use of contraceptives
• legal representative of adult or parent of children understands risks involved with, consent to participate in, and comply with the study procedures

Exclusion Criteria:

• has a history of allergy or anaphylactic reaction to neomycin, gelatin, or any component of VARIVAX^TM
• has received any form of varicella or herpes zoster vaccine at any time prior to study, or anticipates receiving any during study
• has received immune globulin, a blood transfusion or blood derived products within prior 5 months or plans to do so during study
• has received aspirin or any aspirin-containing products within prior 14 days
• has been exposed to varicella or herpes zoster in the prior 4 weeks involving playmate, hospital or continuous household contact, or had contact with a newborn whose mother had chickenpox 5 days before or 2 days after delivery
• has, or lives with a person who has, any congenital or acquired immune deficiency, neoplastic disease, or depressed immunity including those resulting from corticosteroid use or other immunosuppressive therapy
• has received glucocorticosteroids for more than 5 consecutive days within prior 3 months, or any dose of glucocorticoids within prior 7 days, or expects to use glucocorticosteroids during the study
• was vaccinated with licensed non-live or live vaccine within prior 30 days or expects vaccination during 42 day follow-up postvaccination period
• had a fever within 72 hours prior to study vaccination
• has participated in another trial within prior 30 days, is currently participating in another trial, or plans to participate in another trial during the planned study period for this trial
• is pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: VARIVAX™; All participants will receive one dose subcutaneous (SC) VARIVAX™ on Day 1. Adult participants and adolescent participants 13 years and older will also receive a second SC dose VARIVAX™ on Day 43.	Biological: VARIVAX™; VARIVAX™ administered by SC injection as 0.5 mL Varicella Virus Vaccine Live in sterile suspension on Day 1 (all participants) and Day 43 (adult and adolescent participants).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Varicella Zoster Virus (VZV) Antibody Response Rate at 6 Weeks Post Last Vaccination in Participants Who Were Seronegative at Baseline	VZV antibody titers were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA). The VZV antibody response rate was defined as the percentage of participants with a post-vaccination VZV antibody titer ≥5 gpELISA units/mL for participants whose baseline VZV antibody titer was <1.25 gpELISA units/mL. VZV antibody response rate was reported for all study arms at 6 weeks post last vaccination (Vaccination 1 for children and Vaccination 2 for adults and adolescents) for participants who were seronegative to VZW at baseline.	Adults and Adolescents: 6 weeks post Vaccination 2 (up to approximately 86 days), Children: 6 weeks post Vaccination 1 (up to approximately 43 days)
Geometric Mean Titers (GMTs) of VZV Antibodies at 6 Weeks Post Last Vaccination in Participants Who Were Seronegative at Baseline	GMTs of VZV antibodies were measured post-vaccination using a gpELISA. GMT was calculated at each time point by taking the log of the titers, averaging over all participants values, and then back-transforming to the original scale. GMT was reported for all study arms at 6 weeks post last vaccination (Vaccination 1 for children and Vaccination 2 for adults and adolescents) for participants who were seronegative to VZW at baseline.	Adults and Adolescents: 6 weeks post Vaccination 2 (up to approximately 86 days), Children: 6 weeks post Vaccination 1 (up to approximately 43 days)
VZV Antibody Seroconversion Rate at 6 Weeks Post Last Vaccination in Participants Who Were Seronegative at Baseline	VZV antibody levels were measured using a gpELISA. The VZW antibody seroconversion rate was defined as the percentage of participants with VZV antibodies ≥1.25 gpELISA units/mL in participants with a baseline VZV antibody titer <1.25 gpELISA units/mL. VZW antibody seroconversion was reported for all study arms at 6 weeks post last vaccination (Vaccination 1 for children and Vaccination 2 for adults and adolescents) for participants who were seronegative to VZW at baseline.	Adults and Adolescents: 6 weeks post Vaccination 2 (up to approximately 86 days), Children: 6 weeks post Vaccination 1 (up to approximately 43 days)
GMTs of VZV Antibodies at Day 1 and 6 Weeks Post Last Vaccination in Participants Who Were Seropositive at Baseline	GMTs of VZV antibodies were measured post-vaccination using a gpELISA. GMT was calculated at each time point by taking the log of the titers, averaging over all participants values, and then back-transforming to the original scale. GMT was reported for all study arms at 6 weeks post last vaccination (Vaccination 1 for children and Vaccination 2 for adults and adolescents) for participants who were seropositive to VZW at baseline. Per protocol, confidence intervals (CIs) were only calculated when there were at least 5 participants who were seropositive in a treatment group.	Day 1 (Baseline), 6 weeks post last vaccination (Day 43 for children and Day 84 for adults and adolescents)
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titers From Day 1 to 6 Weeks Post Last Vaccination in Participants Who Were Seropositive at Baseline	GMTs were measured using a gpELISA. For participants who were seropositive at baseline (baseline VZV antibody titer ≥1.25 gpELISA units/mL), the GMFR was calculated as the ratio of the VZV GMT at 6 weeks post last vaccination to the VZV GMT at Day 1 (baseline). The GMFR from Day 1 was reported for all study arms at 6 weeks post last vaccination (Vaccination 1 for children and Vaccination 2 for adults and adolescents) for participants who were seropositive to VZW at baseline. Per protocol, CIs were only calculated when there were at least 5 participants who were seropositive in a treatment group.	Day 1 (Baseline), 6 weeks post last vaccination (Day 43 for children and Day 84 for adults and adolescents)
Percentage of Participants With ≥4-Fold Rise in Antibody Titers From Day 1 to 6 Weeks Post Last Vaccination Among Participants Who Were Seropositive at Baseline	GMTs were measured using a gpELISA. For participants who were seropositive at baseline (baseline VZV antibody titer ≥1.25 gpELISA units/mL), the percentage of participants with a ≥4-fold rise in VZV antibody titer from Day 1 (baseline) to post-vaccination was assessed and reported for all study arms at 6 weeks post last vaccination (Vaccination 1 for children and Vaccination 2 for adults and adolescents). Per protocol, CIs were only calculated when there were at least 5 participants who were seropositive in a treatment group.	Day 1 (Baseline), 6 weeks post last vaccination (Day 43 for children and Day 84 for adults and adolescents)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) Post-Vaccination 1	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs, which included erythema, pain, and swelling, were recorded on a Vaccine Report Card (VRC). The percentage of participants who experienced solicited injection-site AEs after Vaccination 1 (up to approximately 5 days post-vaccination) was summarized for all study arms.	Up to approximately 5 days post-Vaccination 1
Percentage of Participants With Solicited Injection-Site AEs Post-Vaccination 2	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs, which included erythema, pain, and swelling, were recorded on a VRC. The percentage of participants who experienced solicited injection-site AEs after Vaccination 2 (up to approximately 5 days post-vaccination) was summarized for all study arms receiving a second vaccination (adults and adolescents).	Up to approximately 5 days post-Vaccination 2 (up to approximately 48 days)
Percentage of Participants With Unsolicited Injection-Site AEs Post-Vaccination 1	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Unsolicited injection-site AEs were recorded on a VRC. The percentage of participants who experienced unsolicited injection-site AEs after Vaccination 1 (up to approximately 42 days post-vaccination) was summarized for all study arms.	Up to approximately 42 days post-Vaccination 1
Percentage of Participants With Unsolicited Injection-Site AEs Post-Vaccination 2	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Unsolicited injection-site AEs were recorded on a VRC. The percentage of participants who experienced unsolicited injection-site AEs after Vaccination 2 (up to approximately 42 days post-vaccination) was summarized for all study arms receiving a second vaccination (adults and adolescents).	Up to approximately 42 days post-Vaccination 2 (up to approximately 86 days)
Percentage of Participants With Elevated Temperature Post-Vaccination 1	The participant's temperature was taken in the evening after Vaccination 1 and daily through Day 28, and was recorded on a VRC. An elevated temperature was defined as ≥39.0 °C (102.2 °F). The percentage of participants with elevated temperature after Vaccination 1 (up to approximately 28 days post-vaccination) was summarized for all study arms.	Up to 28 days post-Vaccination 1
Percentage of Participants With Elevated Temperature Post-Vaccination 2	The participant's temperature was taken in the evening after Vaccination 2 and daily through Day 28, and was recorded on a VRC. An elevated temperature was defined as ≥39.0 °C (102.2 °F). The percentage of participants with elevated temperature after Vaccination 2 (up to approximately 28 days post-vaccination) was summarized for all study arms receiving a second vaccination (adults and adolescents).	Up to 28 days post-Vaccination 2 (up to approximately 71 days)
Percentage of Participants With Varicella- and Herpes Zoster-Like Rashes Post-Vaccination 1	The development of varicella-like and herpes zoster-like rashes was recorded on a VRC. The percentage of participants who experienced varicella-like and herpes zoster-like rashes after Vaccination 1 (up to approximately 42 days post-vaccination) was summarized for all study arms.	Up to approximately 42 days post-Vaccination 1
Percentage of Participants With Varicella- and Herpes Zoster-Like Rashes Post-Vaccination 2	The development of varicella-like and herpes zoster-like rashes was recorded on a VRC. The percentage of participants who experienced varicella-like and herpes zoster-like rashes after Vaccination 2 (up to approximately 42 days post-vaccination) was summarized for all study arms receiving a second vaccination (adults and adolescents).	Up to approximately 42 days post-Vaccination 2 (up to approximately 86 days)
Percentage of Participants With Systemic AEs Post-Vaccination 1	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A systemic AE was defined as any non-injection-site AE. Systemic AEs were recorded on a VRC. The percentage of participants who experienced a systemic AE after Vaccination 1 (up to approximately 42 days post-vaccination) was summarized for all study arms.	Up to approximately 42 days post-Vaccination 1
Percentage of Participants With Systemic AEs Post-Vaccination 2	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A systemic AE was defined as any non-injection-site AE. Systemic AEs were recorded on a VRC. The percentage of participants who experienced a systemic AE after Vaccination 2 (up to approximately 42 days post-vaccination) was summarized for all study arms receiving a second vaccination (adults and adolescents).	Up to approximately 42 days post-Vaccination 2 (up to approximately 86 days)
Percentage of Participants With 1 or More Serious Adverse Events (SAEs) Post-Vaccination 1 or Post-Vaccination 2	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or another important medical event. The percentage of participants who experienced one or more SAEs after either vaccination (up to approximately 42 days post-vaccination) was summarized for all study arms.	Up to 42 days post-Vaccination 1 or post-Vaccination 2 (up to approximately 86 days)
Percentage of Participants With Vaccine-Related SAEs Post-Vaccination 1 or Post-Vaccination 2	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A vaccine-related SAE was an AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or another important medical event, that was considered at least possibly related to the study vaccine. The percentage of participants who experienced one or more vaccine-related SAEs after either vaccination (up to approximately 42 days post-vaccination) was summarized for all study arms.	Up to 42 days post-Vaccination 1 or post-Vaccination 2 (up to approximately 86 days)
Percentage of Participants With Vaccine-Related Death Post-Vaccination 1 or Post-Vaccination 2	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A vaccine-related SAE was an AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or another important medical event, that was considered at least possibly related to the study vaccine. The percentage of participants who experienced a vaccine-related SAE that resulted in death after either vaccination (up to approximately 42 days post-vaccination) was summarized for all study arms.	Up to 42 days post-Vaccination 1 or post-Vaccination 2 (up to approximately 86 days)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Paradis EM, Tikhonov O, Cao X, Kharit SM, Fokin A, Platt HL, Wittke F, Jotterand V. Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX) in healthy infants, children, and adolescents. Hum Vaccin Immunother. 2021 Nov 2;17(11):4183-4189. doi: 10.1080/21645515.2021.1975451. Epub 2021 Oct 26.
• Paradis EM, Tikhonov O, Cao X, Kharit SM, Fokin A, Platt HL, Banniettis N. Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX) in healthy adults. Hum Vaccin Immunother. 2021 Nov 2;17(11):4177-4182. doi: 10.1080/21645515.2021.1957414. Epub 2021 Sep 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2019
• Primary Completion (ACTUAL): June 19, 2020
• Study Completion (ACTUAL): June 19, 2020

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (ACTUAL): February 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 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: V210-058 (OTHER: Merck Protocol Number); 2019-003903-36 (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
• product manufactured in and exported from the U.S.: Yes