Varicella
Conditions
Keywords
Varicella, VarilrixTM
Brief summary
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.
Interventions
BIOLOGICALVarilrixTM
Subcutaneous injection, 2 doses, in the deltoid region of the non-dominant upper arm.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With a Varicella Vaccine Response | At 8 months post-transplantation = 1.5 months post-second dose of vaccination | 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. |
| Anti-varicella Zoster Virus (Anti-VZV) Antibody Titers | At 8 months post-transplantation = 1.5 months post-second dose of vaccination | Antibody titers were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-varicella Antibody Titers | 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) | Antibody titers were were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs). |
| Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | During the 8-day (Days 0-7) post-vaccination period after each dose and across doses | 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. |
| Number of Subjects With Any Fever | During the 43-day (Days 0-42) post-vaccination period after each dose and across doses | 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. |
| Number of Subjects With a Varicella Vaccine Response | At 6.5 months post-transplantation = 2 months post first dose of vaccination | Vaccine response was defined as: for initially seropositive subjects, antibody titer at 6.5 months post-transplantation ≥ 4 fold the pre-vaccination antibody titer. |
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | During the 43-day (Days 0-42) post-vaccination period after each dose and across doses | 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. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the active phase of the study (up to Month 24) | 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. |
| Number of Subjects With Any and Related Rash | During the 43-day (Days 0-42) post-vaccination period after each dose and across doses | 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). |
| Number of Seropositive Subjects for Anti-varicella Antibodies | 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) | The seropositivity cut-off titer of the assay was an anti-VZV antibody titer greater than or equal to (≥) 1:4. |
Countries
Australia
Participant flow
Recruitment details
Subjects in this study were recipients of autologous peripheral stem cell/bone marrow transplants.
Pre-assignment details
Out of the 45 subjects enrolled in the screening phase of the study, 16 subjects did not receive the study vaccine, as they did not meet eligibility criteria, and were hence eliminated from the study active phase.
Participants by arm
| Arm | Count |
|---|---|
| Varilrix Group Subjects with autologous peripheral stem cell/bone marrow transplants, who received 2 doses of Varilrix vaccine subcutaneously in the deltoid region of the non-dominant upper arm, at 4.5 and 6.5 months post-transplantation. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Varilrix Group |
|---|---|
| Age, Continuous | 48.7 Years STANDARD_DEVIATION 9.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 29 |
| other Total, other adverse events | 14 / 29 |
| serious Total, serious adverse events | 5 / 29 |
Outcome results
Primary
Anti-varicella Zoster Virus (Anti-VZV) Antibody Titers
Antibody titers were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs).
Time frame: At 8 months post-transplantation = 1.5 months post-second dose of vaccination
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity measures and assay results for anti-VZV antibodies for Month 8 time point were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Varilrix Group | Anti-varicella Zoster Virus (Anti-VZV) Antibody Titers | 707.5 Titers |
Primary
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.
Time frame: At 8 months post-transplantation = 1.5 months post-second dose of vaccination
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity measures and assay results for anti-varicella zoster virus (VZV) antibodies for Month 8 time point were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varilrix Group | Number of Subjects With a Varicella Vaccine Response | 1 Participants |
Secondary
Anti-varicella Antibody Titers
Antibody titers were were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs).
Time frame: 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)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects. Only those subjects who provided a serum sample at the specified time point (i.e. with anti-VZV antibody assay results available) were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Varilrix Group | Anti-varicella Antibody Titers | Month 0 | 1024.0 Titers |
| Varilrix Group | Anti-varicella Antibody Titers | Month 4.5 | 645.1 Titers |
| Varilrix Group | Anti-varicella Antibody Titers | Month 12 | 380.4 Titers |
| Varilrix Group | Anti-varicella Antibody Titers | Month 24 | 284.8 Titers |
Secondary
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.
Time frame: 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)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects. Only those subjects who provided a serum sample at the specified time point (i.e. with anti-VZV antibody assay results available) were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varilrix Group | Number of Seropositive Subjects for Anti-varicella Antibodies | Month 0 | 15 Participants |
| Varilrix Group | Number of Seropositive Subjects for Anti-varicella Antibodies | Month 4.5 | 15 Participants |
| Varilrix Group | Number of Seropositive Subjects for Anti-varicella Antibodies | Month 12 | 14 Participants |
| Varilrix Group | Number of Seropositive Subjects for Anti-varicella Antibodies | Month 24 | 13 Participants |
Secondary
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.
Time frame: During the 8-day (Days 0-7) post-vaccination period after each dose and across doses
Population: The analysis was performed on the Total vaccinated cohort, which included subjects with at least one vaccination administered. Five subjects who had not completed their symtpom sheets following dose 2 were not included in the analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Pain, Dose 1 | 5 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Pain, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Redness, Dose 1 | 4 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Redness, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Swelling, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Swelling, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Pain, Dose 2 | 4 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Pain, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Redness, Dose 2 | 3 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Redness, Dose 2 | 1 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Swelling, Dose 2 | 1 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Swelling, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Pain, Across Doses | 7 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Pain, Across Doses | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Redness, Across Doses | 6 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Redness, Across Doses | 1 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Any Swelling, Across Doses | 1 Participants |
| Varilrix Group | Number of Subjects With Any and Grade 3 Solicited Local Adverse Events | Grade 3 Swelling, Across Doses | 0 Participants |
Secondary
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).
Time frame: During the 43-day (Days 0-42) post-vaccination period after each dose and across doses
Population: The analysis was performed on the Total vaccinated cohort, which included subjects with at least one vaccination administered. Five subjects who had not completed their symtpom sheets following dose 2 were not included in the analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varilrix Group | Number of Subjects With Any and Related Rash | Rash with Fever, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Any Rash, Dose 1 | 3 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Administration site Rash, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Non-administration site Rash, Dose 1 | 3 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Rash with Fever, Dose 1 | 2 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Measles/Rubella like Rash, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Varicella like Rash, Dose 1 | 1 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Related non-administration site Rash, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Any Rash, Dose 2 | 2 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Administration site Rash, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Non-administration site Rash, Dose 2 | 2 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Measles/Rubella like Rash, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Varicella like Rash, Dose 2 | 1 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Related non-administration site Rash, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Any Rash, Across doses | 5 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Administration site Rash, Across Doses | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Non-administration site Rash, Across Doses | 5 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Rash with Fever, Across Doses | 2 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Measles/Rubella like Rash, Across doses | 0 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Varicella like Rash, Across doses | 2 Participants |
| Varilrix Group | Number of Subjects With Any and Related Rash | Related non-administration site Rash, Across doses | 0 Participants |
Secondary
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.
Time frame: During the 43-day (Days 0-42) post-vaccination period after each dose and across doses
Population: The analysis was performed on the Total vaccinated cohort, which included subjects with at least one vaccination administered. Five subjects who had not completed their symtpom sheets following dose 2 were not included in the analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Varilrix Group | Number of Subjects With Any Fever | Any Fever, Dose 1 | 3 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Grade 3 Fever, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Related Fever, Dose 1 | 0 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Any Fever, Dose 2 | 6 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Grade 3 Fever, Dose 2 | 0 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Related Fever, Dose 2 | 2 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Any Fever, Across doses | 6 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Grade 3 Fever, Across doses | 0 Participants |
| Varilrix Group | Number of Subjects With Any Fever | Related Fever, Across doses | 2 Participants |
Secondary
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.
Time frame: During the 43-day (Days 0-42) post-vaccination period after each dose and across doses
Population: The analysis was performed on the Total vaccinated cohort, which included subjects with at least one vaccination administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varilrix Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 11 Participants |
Secondary
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.
Time frame: At 6.5 months post-transplantation = 2 months post first dose of vaccination
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity measures and assay results for anti-VZV antibodies for Month 6.5 time point were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varilrix Group | Number of Subjects With a Varicella Vaccine Response | 2 Participants |
Secondary
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.
Time frame: During the active phase of the study (up to Month 24)
Population: The analysis was performed on the Total vaccinated cohort, which included subjects with at least one vaccination administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varilrix Group | Number of Subjects With Serious Adverse Events (SAEs) | 5 Participants |