Immunogenicity and Safety of GSK Biologicals' Live Attenuated Varicella Vaccine (VARILRIXTM).

Study Overview
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Brief Summary
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This study aims to assess the immunogenicity and safety of varicella vaccination in a population of autologous peripheral stem cell/ bone marrow transplantation recipients who have reached at least four months post-transplantation.

Official Title
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A Phase III, Open-label, Multi-centre Study to Assess the Immunogenicity and Safety of GlaxoSmithKline Biologicals' Live Attenuated Varicella Vaccine (VarilrixTM), Given as a Primary Vaccination at 4.5 Months and 6.5 Months Post-transplantation, in Autologous Stem Cell/ Bone Marrow Transplant Recipients Aged 18 Years and Older.

Conditions
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Varicella

Intervention / Treatment
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* Biological: VarilrixTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening phase: A male or female ≥ 18 years of age at the time of study entry. Written informed consent obtained from the subject prior to study entry. Patients who are planned to undergo autologous peripheral stem cell/ bone marrow transplantation. Subjects who the investigator believes can and will comply with the requirements of the protocol If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for 10 months after transplantation. Active phase: Patients who are confirmed to have undergone autologous peripheral stem cell/ bone marrow transplantation. If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for 10 months after transplantation. Exclusion Criteria: Screening phase: Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions in the 10 months post-transplantation. History of allergy to any component of the vaccine. Patients with difficult to treat disease who are likely to relapse within 6 months post-transplantation. Current drug and/or alcohol abuse. Active phase: Use of any investigational or non-registered product (drug or vaccine) during the active phase of the study period. Use of immunosuppressants or other immune-modifying drugs within 14 days preceding the administration of the first dose of the study vaccine or planned use during the active phase of the study period. Use of rituximab (MabThera) more than 60 days after transplant. Administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of vaccine and ending 30 days after. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions in the 10 months post-transplantation. History of allergy to any component of the vaccine Patients with VZV disease after transplantation and prior to vaccination. Ongoing requirement for antiviral therapy with anti-VZV activity beyond 4 months post-transplantation Patients with difficult to treat disease who are likely to relapse within 6 months post-transplantation. Current drug and/or alcohol abuse.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varilrix Group<br>Subjects with autologous peripheral stem cell/bone marrow transplants, who received 2 doses of Varilrix vaccine subcutaneously in the deltiod region of the non-dominant upper arm, at 4.5 and 6.5 months post-transplantation. | Biological: VarilrixTM<br>* Subcutaneous injection, 2 doses, in the deltoid region of the non-dominant upper arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Varicella Vaccine Response | Vaccine response was defined as: for initially seropositive subjects, an antibody titer at Month 8 post-transplantation above or equal to (≥) 4 fold the pre-vaccination antibody titer. | At 8 months post-transplantation = 1.5 months post-second dose of vaccination | 
| Anti-varicella Zoster Virus (Anti-VZV) Antibody Titers | Antibody titers were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs). | At 8 months post-transplantation = 1.5 months post-second dose of vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Varicella Vaccine Response | Vaccine response was defined as: for initially seropositive subjects, antibody titer at 6.5 months post-transplantation ≥ 4 fold the pre-vaccination antibody titer. | At 6.5 months post-transplantation = 2 months post first dose of vaccination | 
| Number of Seropositive Subjects for Anti-varicella Antibodies | The seropositivity cut-off titer of the assay was an anti-VZV antibody titer greater than or equal to (≥) 1:4. | At pre-transplantation (Month 0), pre-vaccination visit (at 4.5 months post-transplantation), Month 12 and Month 24 (5.5 and 17.5 months post-second dose of vaccination) | 
| Anti-varicella Antibody Titers | Antibody titers were were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs). | At pre-transplantation (Month 0), pre-vaccination visit (4.5 months post-transplantation), Month 12 and Month 24 (5.5 and 17.5 post-second dose of vaccination) | 
| Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site. | During the 8-day (Days 0-7) post-vaccination period after each dose and across doses | 
| Number of Subjects With Any Fever | Any = fever equal to or greater than (≥) 37.5 °C. Grade 3 fever = fever above (>) 39.0 °C. Related = fever assessed by the investigator as related to the vaccination. | During the 43-day (Days 0-42) post-vaccination period after each dose and across doses | 
| Number of Subjects With Any and Related Rash | Rash was assessed as being either associated to the administration site or not. Non administration site rash was presented by following characteristics (with fever, measles/rubella like, varicella like and related). | During the 43-day (Days 0-42) post-vaccination period after each dose and across doses | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 43-day (Days 0-42) post-vaccination period after each dose and across doses | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the active phase of the study (up to Month 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Varicella, VarilrixTM