A Study to Test GlaxoSmithKline's (GSK) Candidate Vaccine-GSK1437173A for Prevention of Shingles in Children With Kidney Transplant

Overview

The purpose of this study is to evaluate the reactogenicity, safety and immunogenicity of 2 doses of PED-HZ/su, GSK's vaccine candidate for the prevention of Herpes Zoster (HZ) in immunocompromised paediatric renal transplant recipients aged 1-17 years

Eligibility

Inclusion Criteria:

• Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol
• Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
• Written informed assent obtained from the subjects when applicable according to local requirements.
• A male or female between, and including, 1 and 17 years of age at the time of randomisation (Visit Day 1)
• Body weight ≥ 6 kg/13.23 pounds.
• A subject is eligible if they meet at least one of the following criteria:
  • Documented previous VZV vaccination OR
  • Medically verified varicella (with source documentation) OR
  • Seropositive for VZV prior to transplantation.
• Subjects with renal transplant more than six months (180 days) prior randomization

  (Visit Day 1)

• Subject who has received an ABO compatible allogeneic renal transplant (allograft).
• Subject with stable renal function with stability defined as <20% variability between the last two creatinine measurements or based on investigator opinion after review of multiple creatinine measurements.
• Subject receiving maintenance immunosuppressive therapy for the prevention of allograft rejection for a minimum of one month (30 days) prior to randomization (Visit Day 1).
• Female subjects of childbearing potential may be enrolled in the study, if the subject
  • has practiced adequate contraception for 30 days prior to Visit Day 1 and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series

Exclusion Criteria:

Medical conditions

• Any primary kidney disease with a high incidence of recurrent primary kidney disease within the allograft
• Evidence of recurrent primary kidney disease within the current allograft
• Previous allograft loss secondary to recurrent primary kidney disease
• History of more than one organ transplanted (that is, kidney-liver, simultaneous double kidney or kidney-other organ(s) transplanted).
• Subjects with an episode of acute allograft rejection over the six months (180 days) prior to enrolment
• Panel Reactive Antibodies (PRA) calculated PRA (cPRA) or Calculated Reaction Frequency (cRF) score that is unknown at the time of transplant
• VZV serostatus unknown prior to transplant
• Subjects with advanced chronic kidney disease
• Evidence of significant proteinuria (≥ 200 g/mol creatinine) believed to be of renal origin (an example of non-renal origin is proteinuria from mucus in a reconstructed bladder)
• Subjects without multiple dialysis options in the event acute or chronic dialysis needed.
• History of unstable or progressive neurological disorder.
• Subjects ≤ 5 years of age with a history of one or more simple or complex febrile seizures
• Subjects > 5 years with history of one or more complex febrile seizures
• Occurrence of a varicella or HZ episode by clinical history within the 6 months (180 days) preceding Visit Day 1
• Any autoimmune disease, with the following exceptions which do not constitute an exclusion criterion:
  • IgA nephropathy
  • Rapidly progressive glomerulonephritis
  • Membranous glomerulonephritis
  • Idiopathic Type I membranoproliferative glomerulonephritis
  • Diabetes mellitus (type 1 and 2) with diabetic nephropathy
• Confirmed or suspected Human Immunodeficiency Virus or primary immunodeficiency

  disease

• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine
• Any condition which, in the judgement of the investigator would make intramuscular injection unsafe.
• Atypical Haemolytic Uraemic Syndrome.

Prior/Concomitant therapy

• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before Visit Day 1 (Day -29 to Day -1), or planned use during the study period.
• Subject in receipt of treatment for rejection during the six months (180 days) prior to enrolment.
• Use of anti-CD20 or other B-cell monoclonal antibody agents within 1 year of Visit Day 1 or planned administration during the duration of the study.
• Administration of blood products 3 months (90 days) prior to Visit Day 1 or planned administration during the duration of the study.
• Administration of immunoglobulins 6 months (180 days) prior to Visit Day 1 or planned administration of immunoglobulins during the duration of the study.
• Administration or planned administration of a vaccine within 30 days prior to Visit Day 1 up to Visit Month 2 with the exception of an inactivated or subunit influenza vaccine which may be given 8 days prior to or 14 days after Visit Day 1 and 8 days prior to or 14 days after Visit Month 1.
• Previous vaccination against HZ
• Varicella vaccination within the 6 months (180 days) preceding Visit Day 1
• Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine

Prior/Concurrent clinical study experience

        • Concurrent or planned participation in another clinical study, at any time during the
        study period, in which the subject has been or will be exposed to an investigational or a
        non-investigational product
          -  available locally through compassionate use programs,
          -  submitted for and pending local/country registration,
          -  approved and registered for use in other countries with well-documented Summary of
             Product Characteristics or Prescribing Information
          -  The name of the active component(s) of these immunosuppressants must be provided in
             the concomitant medication listing
        Other exclusions
          -  Child in care
          -  Pregnant or lactating female
          -  Female planning to become pregnant or planning to discontinue contraceptive
             precautions (if of childbearing potential) between one month (30 days) prior to Visit
             Day 1 through two months (60 days) after Visit Month 1.
          -  Evidence or high suspicion, in the opinion of the investigator, of non-compliance or
             non-adherence to use of induction and/or maintenance immunosuppressive therapies.
          -  Failure to fully complete the 7-day pre-vaccination diary card distributed at the
             Pre-vaccination visit
               -  Completion must cover the 7 days immediately prior to randomisation (Visit Day
                  1).
               -  Completion is defined as a minimum of 6 days completed.
               -  Subjects with less than 6 days completed may be offered a new date for Visit Day
                  1 and the opportunity to comply with the completion of the 7-day pre-vaccination
                  diary card prior to the new planned Visit Day 1.
          -  Any study personnel or their immediate dependants, family, or household member.