Clinical trial NCT04006808: A Study to Test GlaxoSmithKline's (GSK) Candidate Vaccine-GSK1437173A for Prevention of Shingles in Children With Kidney Transplant
Official title: A Reactogenicity, Safety and Immunogenicity Study of GSK's Paediatric Herpes Zoster Subunit Candidate Vaccine (PED-HZ/su) GSK143713A in Immunocompromised Paediatric Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Herpes Zoster
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-07-05
Enrollment: 184
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: 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 criteria: 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.

Primary outcomes:
measure: Number of subjects from the interventional groups, with solicited local adverse events (AEs)
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the interventional groups, with solicited general AEs
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the control groups with solicited general symptoms
timeFrame: Within 7 days after Visit Day 1
measure: Number of subjects from the control groups with solicited general symptoms
timeFrame: Within 7 days after Visit Month 1
measure: Number of subjects from the interventional groups with unsolicited AEs after each vaccination
timeFrame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the control groups with unsolicited symptoms
timeFrame: Within 30 days after Visit Day 1
measure: Number of subjects from the control groups with unsolicited symptoms
timeFrame: Within 30 days after Visit Month 1
measure: Number of subjects with serious adverse events (SAEs), potential immune mediated diseases (pIMDs) and biopsy confirmed renal allograft rejection.
timeFrame: From Visit Day 1 up to Visit Month 2
measure: Number of subjects from the interventional groups with seizures
timeFrame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional groups with seizures
timeFrame: Within 30 days after Visit Day 1
measure: Number of subjects from the non-interventional groups with seizures
timeFrame: Within 30 days after Visit Month 1
measure: Number of subjects from the interventional groups with generalized convulsive seizures
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional groups with generalized convulsive seizures
timeFrame: Within 7 days after Visit Day 1
measure: Number of subjects from the non-interventional groups with generalized convulsive seizures
timeFrame: Within 7 days after Visit Month 1
measure: Percentage of subjects with Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs)
timeFrame: At Month 2 (one-month post-dose 2)
Secondary outcomes:
measure: Number of subjects with SAEs, pIMDs and biopsy confirmed renal allograft rejections from day 1 to month 13
timeFrame: From Visit Day 1 up to Visit Month 13
measure: Occurrence of Herpes Zoster cases
timeFrame: From Visit Day 1 until Visit Month 13
measure: Number of subjects from the interventional pooled age group with solicited local AEs
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the interventional pooled age group with solicited general AEs
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional pooled age group with solicited general symptoms
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the interventional pooled age group with unsolicited AEs after each vaccination
timeFrame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional pooled age group with unsolicited symptoms
timeFrame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional pooled age group with unsolicited symptoms
timeFrame: Within 30 days after Visit Month 1
measure: Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections
timeFrame: From Visit Day 1 until Visit Month 2
measure: Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections
timeFrame: From Visit Day 1 until Visit Month 13
measure: Number of subjects from the pooled age groups with HZ
timeFrame: From Visit Day 1 until Visit Month 13
measure: Number of subjects from the interventional pooled age group with seizures
timeFrame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional pooled age group with seizures
timeFrame: Within 30 days after Visit Day 1
measure: Number of subjects from the non-interventional pooled age group with seizures
timeFrame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the interventional pooled age group with generalized convulsive seizures
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional pooled age group with generalized convulsive seizures
timeFrame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
measure: Number of subjects from the non-interventional pooled age group with generalized convulsive seizures
timeFrame: Within 7 days after Visit Month 1
measure: Vaccine Response Rate (VRR) for Anti-glycoprotein (Anti-gE) antibody concentrations
timeFrame: At Month 2 and Month 13
measure: Median fold increase of anti-gE antibody concentrations
timeFrame: At Month 2 and Month 13
measure: Percentage of subjects with anti-gE antibody concentrations in terms of GMCs
timeFrame: At Day 1 (pre-vaccination) and Month 13
measure: Percentage of subjects in the interventional pooled age group, with Anti-gE antibody concentrations in terms of GMCs
timeFrame: At Day 1, Month 2 and Month 13
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liege
country: Belgium
facility: GSK Investigational Site
city: Bordeaux cedex
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Marseille cedex 5
country: France
facility: GSK Investigational Site
city: Montpellier cedex
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Torino
country: Italy
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: BaracaldoVizcaya
country: Spain
facility: GSK Investigational Site
city: Espluges De Llobregat
country: Spain
facility: GSK Investigational Site
city: HebrOn
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Cardiff
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow Strathclyde
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: