Trial Outcomes & Findings for Immunogenicity and Safety of GSK Biologicals' Live Attenuated Varicella Vaccine (VARILRIXTM). (NCT NCT00792623)

Last Updated: 2018-11-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

At 8 months post-transplantation = 1.5 months post-second dose of vaccination

Results posted on

2018-11-08

Participant Flow

Subjects in this study were recipients of autologous peripheral stem cell/bone marrow transplants.

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	29
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varilrix Group n=29 Participants 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.
Age, Continuous	48.7 Years STANDARD_DEVIATION 9.65 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Varilrix Group n=15 Participants 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.
Number of Subjects With a Varicella Vaccine Response	1 Participants

PRIMARY outcome

Timeframe: 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.

Antibody titers were measured by Indirect Immunofluorescence Assay (IFA) and presented as geometric mean titers (GMTs).

Outcome measures

Outcome measures
Measure	Varilrix Group n=15 Participants 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.
Anti-varicella Zoster Virus (Anti-VZV) Antibody Titers	707.5 Titers Interval 308.0 to 1625.5

SECONDARY outcome

Timeframe: 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.

Vaccine response was defined as: for initially seropositive subjects, antibody titer at 6.5 months post-transplantation ≥ 4 fold the pre-vaccination antibody titer.

Outcome measures

Outcome measures
Measure	Varilrix Group n=10 Participants 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.
Number of Subjects With a Varicella Vaccine Response	2 Participants

SECONDARY outcome

Timeframe: 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.

The seropositivity cut-off titer of the assay was an anti-VZV antibody titer greater than or equal to (≥) 1:4.

Outcome measures

Outcome measures
Measure	Varilrix Group n=15 Participants 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.
Number of Seropositive Subjects for Anti-varicella Antibodies Month 0	15 Participants
Number of Seropositive Subjects for Anti-varicella Antibodies Month 4.5	15 Participants
Number of Seropositive Subjects for Anti-varicella Antibodies Month 12	14 Participants
Number of Seropositive Subjects for Anti-varicella Antibodies Month 24	13 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Varilrix Group n=15 Participants 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.
Anti-varicella Antibody Titers Month 0	1024.0 Titers Interval 481.8 to 2176.2
Anti-varicella Antibody Titers Month 4.5	645.1 Titers Interval 264.8 to 1571.5
Anti-varicella Antibody Titers Month 12	380.4 Titers Interval 164.0 to 882.2
Anti-varicella Antibody Titers Month 24	284.8 Titers Interval 103.8 to 781.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Varilrix Group n=29 Participants 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.
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Pain, Dose 1	5 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Pain, Dose 1	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Redness, Dose 1	4 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Redness, Dose 1	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Swelling, Dose 1	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Swelling, Dose 1	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Pain, Dose 2	4 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Pain, Dose 2	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Redness, Dose 2	3 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Redness, Dose 2	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Swelling, Dose 2	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Swelling, Dose 2	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Pain, Across Doses	7 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Pain, Across Doses	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Redness, Across Doses	6 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Redness, Across Doses	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Any Swelling, Across Doses	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Adverse Events Grade 3 Swelling, Across Doses	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Varilrix Group n=29 Participants 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.
Number of Subjects With Any Fever Any Fever, Dose 1	3 Participants
Number of Subjects With Any Fever Grade 3 Fever, Dose 1	0 Participants
Number of Subjects With Any Fever Related Fever, Dose 1	0 Participants
Number of Subjects With Any Fever Any Fever, Dose 2	6 Participants
Number of Subjects With Any Fever Grade 3 Fever, Dose 2	0 Participants
Number of Subjects With Any Fever Related Fever, Dose 2	2 Participants
Number of Subjects With Any Fever Any Fever, Across doses	6 Participants
Number of Subjects With Any Fever Grade 3 Fever, Across doses	0 Participants
Number of Subjects With Any Fever Related Fever, Across doses	2 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Varilrix Group n=29 Participants 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.
Number of Subjects With Any and Related Rash Any Rash, Dose 1	3 Participants
Number of Subjects With Any and Related Rash Administration site Rash, Dose 1	0 Participants
Number of Subjects With Any and Related Rash Non-administration site Rash, Dose 1	3 Participants
Number of Subjects With Any and Related Rash Rash with Fever, Dose 1	2 Participants
Number of Subjects With Any and Related Rash Measles/Rubella like Rash, Dose 1	0 Participants
Number of Subjects With Any and Related Rash Varicella like Rash, Dose 1	1 Participants
Number of Subjects With Any and Related Rash Related non-administration site Rash, Dose 1	0 Participants
Number of Subjects With Any and Related Rash Any Rash, Dose 2	2 Participants
Number of Subjects With Any and Related Rash Administration site Rash, Dose 2	0 Participants
Number of Subjects With Any and Related Rash Non-administration site Rash, Dose 2	2 Participants
Number of Subjects With Any and Related Rash Rash with Fever, Dose 2	0 Participants
Number of Subjects With Any and Related Rash Measles/Rubella like Rash, Dose 2	0 Participants
Number of Subjects With Any and Related Rash Varicella like Rash, Dose 2	1 Participants
Number of Subjects With Any and Related Rash Related non-administration site Rash, Dose 2	0 Participants
Number of Subjects With Any and Related Rash Any Rash, Across doses	5 Participants
Number of Subjects With Any and Related Rash Administration site Rash, Across Doses	0 Participants
Number of Subjects With Any and Related Rash Non-administration site Rash, Across Doses	5 Participants
Number of Subjects With Any and Related Rash Rash with Fever, Across Doses	2 Participants
Number of Subjects With Any and Related Rash Measles/Rubella like Rash, Across doses	0 Participants
Number of Subjects With Any and Related Rash Varicella like Rash, Across doses	2 Participants
Number of Subjects With Any and Related Rash Related non-administration site Rash, Across doses	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Varilrix Group n=29 Participants 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.
Number of Subjects With Any Unsolicited Adverse Events (AEs)	11 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Varilrix Group n=29 Participants 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.
Number of Subjects With Serious Adverse Events (SAEs)	5 Participants

Adverse Events

Varilrix Group

Serious events: 5 serious events

Other events: 14 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Varilrix Group n=29 participants at risk 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.
Blood and lymphatic system disorders Pancytopenia	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
General disorders Chest pain	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Infections and infestations Pharyngitis	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Infections and infestations Pneumonia	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid adenoma	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Nervous system disorders Transient ischaemic attack	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Respiratory, thoracic and mediastinal disorders Upper airway obstruction	3.4% 1/29 • Number of events 1 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.

Other adverse events

Other adverse events
Measure	Varilrix Group n=29 participants at risk 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.
Musculoskeletal and connective tissue disorders Back pain	10.3% 3/29 • Number of events 4 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Gastrointestinal disorders Diarrhoea	6.9% 2/29 • Number of events 2 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Skin and subcutaneous tissue disorders Erythema	20.7% 6/29 • Number of events 7 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
General disorders Injection site pruritus	6.9% 2/29 • Number of events 2 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Infections and infestations Nasopharyngitis	6.9% 2/29 • Number of events 2 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
General disorders Pain	24.1% 7/29 • Number of events 9 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.
Infections and infestations Upper respiratory tract infection	6.9% 2/29 • Number of events 2 • Solicited symptoms: during the 8-day (Days 0-7) post-vaccination period; Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; Serious adverse events (SAEs): during the entire study, up to Month 24 post-transplantation.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER