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

NCT04006808 | Recruiting Phase 1 DMC

• 2 other identifiers: 2000752019-000607-33
• Study Type: interventional
• Target: 184
• Locations: 6 countries
• Sites: 31

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

Conditions

Herpes Zoster

Outcome Measures

Primary Outcomes (15)

• Number of subjects from the interventional groups, with solicited local adverse events (AEs)

  Assessed solicited local AEs are pain, redness and swelling at the injection site. Pain includes tenderness. Note: GSK diary cards for collecting solicited local and general AEs/symptoms is different for subjects \< 6 years and ≥ 6 years. Hence the age category of 1-11 years is further split to 1-5 years and 6-11 years.

  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

  Assessed solicited general AEs among Infants/Toddlers/Children \< 6 years are: * Drowsiness * Fever\* * Irritability/Fussiness * Loss of appetite * Gastrointestinal (GI) symptoms\*\* Assessed solicited general AEs among Children ≥ 6 years are: * Fatigue * Fever\* * GI symptoms\*\* * Headache * Myalgia * Shivering (chills) * Fever is defined as temperature ≥ 38.0°C/100.4°F \*\*GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain Note: GSK diary cards for collecting solicited local and general AEs/symptoms is different for subjects \< 6 years and ≥ 6 years. Hence the age category of 1-11 years is further split to 1-5 years and 6-11 years.

  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

  Assessed solicited general symptoms among Infants/Toddlers/Children \< 6 years are: * Drowsiness * Fever\* * Irritability/Fussiness * Loss of appetite * GI symptoms\*\* Assessed solicited general symptoms among Children ≥ 6 years are: * Fatigue * Fever\* * GI symptoms\*\* * Headache * Myalgia * Shivering (chills) * Fever is defined as temperature ≥ 38.0°C/100.4°F \*\*GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain As subjects from the control group are not vaccinated, they will not complete the diary card for local solicited symptoms.

  Within 7 days after Visit Day 1

• Number of subjects from the control groups with solicited general symptoms

  Assessed solicited general symptoms among Infants/Toddlers/Children \< 6 years are: * Drowsiness * Fever\* * Irritability/Fussiness * Loss of appetite * GI symptoms\*\* Assessed solicited general symptoms among Children ≥ 6 years are: * Fatigue * Fever\* * GI symptoms\*\* * Headache * Myalgia * Shivering (chills) * Fever is defined as temperature ≥ 38.0°C/100.4°F \*\*GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain

  Within 7 days after Visit Month 1

• Number of subjects from the interventional groups with unsolicited AEs after each vaccination

  An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event.

  Within 30 days after each vaccination (vaccines administered on day 1 and month 1)

• Number of subjects from the control groups with unsolicited symptoms

  An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event.

  Within 30 days after Visit Day 1

• Number of subjects from the control groups with unsolicited symptoms

  An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event.

  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.

  An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. pIMDs are sub sets of Adverse events of special interest (AESIs) that include autoimmune disease and other inflammatory and/neurological disorders of interest, which may or may not have autoimmune aetiology. The renal allograft rejections are biopsy confirmed pathophysiological changes indicative of rejection. The rejection is graded for severity and extent of histologic inflammation and injury. The reporting period for any renal allograft rejection is from Visit Day 1 to the study end (month 2).

  From Visit Day 1 up to Visit Month 2

• Number of subjects from the interventional groups with seizures

  All seizures occurring within 30 days following study vaccination are reported.

  Within 30 days after each vaccination (vaccines administered on day 1 and month 1)

• Number of subjects from the non-interventional groups with seizures

  All seizures occurring within 30 days after visit day 1 are reported, for the control groups.

  Within 30 days after Visit Day 1

• Number of subjects from the non-interventional groups with seizures

  All seizures occurring within 30 days of visit month 1 are reported, for the control groups

  Within 30 days after Visit Month 1

• Number of subjects from the interventional groups with generalized convulsive seizures

  Generalized convulsive seizures are classified as follows: * Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations * Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above * Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure.

  Within 7 days after each vaccination (vaccines administered on day 1 and month 1)

• Number of subjects from the non-interventional groups with generalized convulsive seizures

  Generalized convulsive seizures are classified as follows: * Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations * Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above * Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure

  Within 7 days after Visit Day 1

• Number of subjects from the non-interventional groups with generalized convulsive seizures

  Generalized convulsive seizures are classified as follows: * Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations * Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above * Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure

  Within 7 days after Visit Month 1

• Percentage of subjects with Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs)

  The geometric mean concentration (GMC) calculations are performed by taking the anti log of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value equal to half the cut-off for GMC calculation

  At Month 2 (one-month post-dose 2)

Secondary Outcomes (21)

• Number of subjects with SAEs, pIMDs and biopsy confirmed renal allograft rejections from day 1 to month 13

  From Visit Day 1 up to Visit Month 13

• Occurrence of Herpes Zoster cases

  From Visit Day 1 until Visit Month 13

• Number of subjects from the interventional pooled age group with solicited local AEs

  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

  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

  Within 7 days after each vaccination (vaccines administered on day 1 and month 1)

Study Arms (4)

PED-HZ/su 12-17 Group

EXPERIMENTAL

Paediatric renal transplant recipients aged 12 to 17 years old, receiving 2 doses of the investigational vaccine (PED HZ/su)

Biological: PED-HZ/su

Control 12-17 Group

NO INTERVENTION

Paediatric renal transplant recipients aged 12 to 17 years old, not receiving the investigational vaccine but being treated according to the local standard of care

PED-HZ/su 1-11 Group

EXPERIMENTAL

Paediatric renal transplant recipients aged 1 to 11 years old, receiving 2 doses of the investigational vaccine (PED HZ/su). Enrolment into this group will be in a staggered manner. Following enrolment into the PED-HZ/su 12-17 group, a safety evaluation of data collected up to visit month 2 will be performed. Upon favourable outcome of the evaluation, enrolment into this group will begin.

Biological: PED-HZ/su

Control 1-11 Group

NO INTERVENTION

Paediatric renal transplant recipients aged 1 to 11 years old, not receiving the investigational vaccine but being treated according to the local standard of care

Interventions

PED-HZ/su BIOLOGICAL

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.

PED-HZ/su 1-11 Group; PED-HZ/su 12-17 Group

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (31)

GSK Investigational Site

Brussels, 1020, Belgium

RECRUITING

GSK Investigational Site

Ghent, 9000, Belgium

RECRUITING

GSK Investigational Site

Leuven, 3000, Belgium

RECRUITING

GSK Investigational Site

Liège, 4000, Belgium

RECRUITING

GSK Investigational Site

Bordeaux, 33000, France

RECRUITING

GSK Investigational Site

Lille, 59000, France

RECRUITING

GSK Investigational Site

Marseille, 13385, France

RECRUITING

GSK Investigational Site

Montpellier, 34295, France

RECRUITING

GSK Investigational Site

Nantes, 44093, France

WITHDRAWN

GSK Investigational Site

Paris, 75015, France

RECRUITING

GSK Investigational Site

Paris, 75019, France

RECRUITING

GSK Investigational Site

Toulouse, 31059, France

RECRUITING

GSK Investigational Site

Genova, 16147, Italy

COMPLETED

GSK Investigational Site

Milan, 20122, Italy

RECRUITING

GSK Investigational Site

Padua, 35128, Italy

RECRUITING

GSK Investigational Site

Roma, 00165, Italy

RECRUITING

GSK Investigational Site

Torino, 10126, Italy

RECRUITING

GSK Investigational Site

Gdansk, 80-952, Poland

RECRUITING

GSK Investigational Site

BaracaldoVizcaya, 48903, Spain

RECRUITING

GSK Investigational Site

Espluges de Llobregat, 08950, Spain

COMPLETED

GSK Investigational Site

HebrOn, 08035, Spain

RECRUITING

GSK Investigational Site

Madrid, 28007, Spain

RECRUITING

GSK Investigational Site

Madrid, 28046, Spain

RECRUITING

GSK Investigational Site

Seville, 41013, Spain

RECRUITING

GSK Investigational Site

Birmingham, B4 6NH, United Kingdom

COMPLETED

GSK Investigational Site

Cardiff, CF14 4XW, United Kingdom

COMPLETED

GSK Investigational Site

Glasgow Strathclyde, G51 4TF, United Kingdom

RECRUITING

GSK Investigational Site

London, WC1N 3JH, United Kingdom

RECRUITING

GSK Investigational Site

Manchester, M13 9WL, United Kingdom

RECRUITING

GSK Investigational Site

Nottingham, NG7 2UH, United Kingdom

RECRUITING

GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Herpes Zoster

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 5, 2019
• Study Start: October 25, 2019
• Primary Completion: May 1, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

PL (1); BE (4); ES (6); GB (7); FR (8); IT (5)