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

Официальное название

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

Обзор

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

Вмешательства

• Биопрепарат PED-HZ/su
  GSK's candidate vaccine- PED-HZ/su. is administered intramuscularly in the deltoid of the non-dominant arm, on a two-dose schedule in the two investigational groups.

Первичные конечные точки

• Number of subjects from the interventional groups, with solicited local adverse events (AEs) [Срок оценки: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the interventional groups, with solicited general AEs [Срок оценки: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the control groups with solicited general symptoms [Срок оценки: Within 7 days after Visit Day 1]
• Number of subjects from the control groups with solicited general symptoms [Срок оценки: Within 7 days after Visit Month 1]
• Number of subjects from the interventional groups with unsolicited AEs after each vaccination [Срок оценки: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the control groups with unsolicited symptoms [Срок оценки: Within 30 days after Visit Day 1]
• Number of subjects from the control groups with unsolicited symptoms [Срок оценки: Within 30 days after Visit Month 1]
• Number of subjects with serious adverse events (SAEs), potential immune mediated diseases (pIMDs) and biopsy confirmed renal allograft rejection. [Срок оценки: From Visit Day 1 up to Visit Month 2]
• Number of subjects from the interventional groups with seizures [Срок оценки: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the non-interventional groups with seizures [Срок оценки: Within 30 days after Visit Day 1]

Вторичные конечные точки (12)

• Number of subjects with SAEs, pIMDs and biopsy confirmed renal allograft rejections from day 1 to month 13 [Срок оценки: From Visit Day 1 up to Visit Month 13]
• Occurrence of Herpes Zoster cases [Срок оценки: From Visit Day 1 until Visit Month 13]
• Number of subjects from the interventional pooled age group with solicited local AEs [Срок оценки: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the interventional pooled age group with solicited general AEs [Срок оценки: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the non-interventional pooled age group with solicited general symptoms [Срок оценки: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the interventional pooled age group with unsolicited AEs after each vaccination [Срок оценки: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the non-interventional pooled age group with unsolicited symptoms [Срок оценки: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)]
• Number of subjects from the non-interventional pooled age group with unsolicited symptoms [Срок оценки: Within 30 days after Visit Month 1]
• Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections [Срок оценки: From Visit Day 1 until Visit Month 2]
• Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections [Срок оценки: From Visit Day 1 until Visit Month 13]
• Number of subjects from the pooled age groups with HZ [Срок оценки: From Visit Day 1 until Visit Month 13]
• Number of subjects from the interventional pooled age group with seizures [Срок оценки: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)]

Критерии участия

Критерии включения

• 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

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Франция · 8 центров

• GSK Investigational Site — Bordeaux
• GSK Investigational Site — Lille
• GSK Investigational Site — Marseille
• GSK Investigational Site — Montpellier
• GSK Investigational Site — Nantes
• GSK Investigational Site — Paris
• GSK Investigational Site — Paris
• GSK Investigational Site — Toulouse

Великобритания · 7 центров

• GSK Investigational Site — Birmingham
• GSK Investigational Site — Cardiff
• GSK Investigational Site — Glasgow Strathclyde
• GSK Investigational Site — London
• GSK Investigational Site — Manchester
• GSK Investigational Site — Nottingham
• GSK Investigational Site — Southampton

Испания · 6 центров

• GSK Investigational Site — BaracaldoVizcaya
• GSK Investigational Site — Espluges de Llobregat
• GSK Investigational Site — HebrOn
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Seville

Италия · 5 центров

• GSK Investigational Site — Genova
• GSK Investigational Site — Milan
• GSK Investigational Site — Padova
• GSK Investigational Site — Roma
• GSK Investigational Site — Torino

Бельгия · 4 центра

• GSK Investigational Site — Brussels
• GSK Investigational Site — Ghent
• GSK Investigational Site — Leuven
• GSK Investigational Site — Liège

Польша · 1 центр

• GSK Investigational Site — Gdansk

Публикации

• Mollo A, Peri M, Lodi L, Gissi A, Lionetti P, Marrani E, Mastrolia MV, Tondo A, Tintori V, Sardi I, Indolfi G, Trapani S, Galli L, Venturini E, Astorino V, Azzari C, Ricci S. Considering recombinant herpes zoster vaccine for fragile pediatric patients: A new opportunity. Vaccine. 2025 Apr 19;53:127072. doi: 10.1016/j.vaccine.2025.127072. Epub 2025 Apr 7. PMID 40198934

Идентификаторы

NCT: NCT04006808 · 200075 · 2019-000607-33

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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