A Phase II, randomised, open-label, multicentre study to assess the reactogenicity, safety and immunogenicity of GSK's paediatric Herpes Zoster subunit candidate vaccine (PED-HZ/su) when administered intramuscularly on a two-dose schedule to immunocompromised paediatric renal transplant recipients from 1 to 17 years of age.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GlaxoSmithKline Biologicals

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Sep 2019 → ongoing

Decision date (initial)

2023-12-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502784-37-00

EudraCT number

2019-000607-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the reactogenicity (up to Day 7) and safety (up to Month 2) following administration of PED-HZ/su in each age category (1-11 and 12-17 years);
To evaluate humoral immune responses following administration of PED-HZ/su in each age category (1-11 and 12-17 years) at Month 2.

Secondary objectives 4

1. To evaluate safety following administration of PED-HZ/su in each age category (1-11 and 12-17 years) from Day 1 up to Month 13;
2. To describe the occurrence of cases of HZ in each age category (1-11 and 12-17 years);
3. To evaluate reactogenicity and safety for the entire study population (1-17 years) following administration of PED-HZ/su;
4. To characterise humoral immune responses following administration of PED-HZ/su.

Conditions and MedDRA coding

Prevention of Herpes Zoster in immunocompromised subjects aged 1-17 years

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001426-PIP01-13

Plan to share IPD

Yes

IPD plan description

o IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf o IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months. o IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. • 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 (For example, completion of the diary cards, return for follow-up visits).
2. • 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.
3. • Written informed assent obtained from the subjects when applicable according to local requirements.
4. • A male or female between, and including, 1 and 17 years of age at the time of randomisation (Visit Day 1)
5. • Body weight ≥ 6 kg/13.23 pounds.
6. • 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.
7. • Subjects with renal transplant more than six months (180 days) prior randomisation (Visit Day 1)
8. • Subject who has received an ABO compatible allogeneic renal transplant (allograft).
9. • 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.
10. • Subject receiving maintenance immunosuppressive therapy (refer to Glossary of terms for definition) for the prevention of allograft rejection for a minimum of one month (30 days) prior to randomisation (Visit Day 1).
11. • 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 (note that abstinence is a method of contraception as defined in Section 12.6.2 of the protocol)..

Exclusion criteria 36

1. • Any primary kidney disease with a high incidence of recurrent primary kidney disease within the allograft.
2. • Administration of immunoglobulins 6 months (180 days) prior to Visit Day 1 or planned administration of immunoglobulins during the duration of the study.
3. • 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.
4. • 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).
5. • Any condition which, in the judgement of the investigator would make intra-muscular (IM) injection unsafe.
6. • PRA or cPRA or cRF score that is unknown at the time of transplant.
7. • VZV serostatus unknown prior to transplant.
8. • Subjects with advanced chronic kidney disease (CKD) (that is, estimated GFR by the bedside CKD in children equation of less than 30 mL/min/1.73 m2).
9. • Subjects > 5 years with history of one or more complex febrile seizures.
10. • Occurrence of a varicella or HZ episode by clinical history within the 6 months (180 days) preceding Visit Day 1.
11. • 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 (MPGN) - Diabetes mellitus (type 1 and 2) with diabetic nephropathy
12. History of more than one organ transplanted (that is, kidney-liver, simultaneous double kidney or kidney-other organ(s) transplanted).
13. • Previous vaccination against HZ.
14. • Varicella vaccination within the 6 months (180 days) preceding Visit Day 1.
15. • Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
16. • History of unstable or progressive neurological disorder.
17. • Subjects <= 5 years of age with a history of one or more simple or complex febrile seizures.
18. Atypical Haemolytic Uraemic Syndrome.
19. • Use of any investigational or non-registered product‡ (drug, vaccine or medical device) 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.
20. • Subjects without multiple dialysis options (that is peritoneal and/or more than one anatomical access site for haemodialysis) in the event acute or chronic dialysis needed.
21. • Evidence of recurrent primary kidney disease within the current allograft.
22. • Previous allograft loss secondary to recurrent primary kidney disease.
23. Subjects with an episode of acute allograft rejection over the six months (180 days) prior to enrolment.
24. 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‡ (drug or medical device). ‡The only exception would be use of investigational or non-registered immunosuppressant(s), at the local/country level, which may be used if they are specifically prescribed for the prevention of allograft rejection and are: - 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 (SmPC) or Prescribing Information (PI). - The name of the active component(s) of these immunosuppressants must be provided in the concomitant medication listing.
25. • Child in care (Please refer to the glossary of terms in the protocol for the definition of child in care).
26. • Pregnant or lactating female.
27. • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
28. • Confirmed or suspected HIV or primary immunodeficiency disease.
29. • Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
30. • Subject in receipt of treatment for rejection during the six months (180 days) prior to enrolment.
31. • Use of anti-CD20 or other B-cell monoclonal antibody agents (For example, rituximab) within 1 year of Visit Day 1 or planned administration during the duration of the study.
32. • Administration of blood products 3 months (90 days) prior to Visit Day 1 or planned administration during the duration of the study.
33. • 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.
34. • 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.
35. • 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.
36. • Any study personnel or their immediate dependants, family, or household member.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Occurrence of solicited loc. AEs and solicited gen. AEs/symptoms in subj. aged 1-11 and 12-17 years. For vaccinated subj., occurrence, intensity and duration of each solicited local AE within 7D after each vac. For vaccinated subj., occurrence, intensity, duration and relationship to vaccination of each solicited general AE within 7D after each vaccination. For non-interventional control group, occurrence, intensity and duration of each solicited gen. symptoms within 7D of VD1 and VM1.
2. Occurrence of unsolicited AEs/symptoms in subj aged 1-11 and 12-17 years. - For vaccinated subj, occurrence, intensity, duration and relationship to vaccination of unsolicited AEs during 30D after each vaccination, classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. - For non-interventional control group, occurrence, intensity and duration of unsolicited symptoms during 30D after VD1 and VM1 classified according to MedDRA classification.
3. Occurrence of SAEs, pIMDs and renal allograft rejection in subjects aged 1-11 and 12-17 years. - For vaccinated subjects, the occurrence and relationship to vaccination of all SAEs, pIMDs and biopsy-confirmed renal allograft rejection from Visit Day 1 (first vaccination) up to Visit Month 2 (one month post-dose 2). - For the non-interventional control group, the occurrence of all SAEs, pIMDs and biopsy-confirmed renal allograft rejection from Visit Day 1 up to Visit Month 2.
4. Occurrence of seizures in subjects 1-11 and 12-17 years. - For vaccinated subjects, the occurrence, intensity, duration and relationship to vaccination of seizures during the 30 days after each vaccination, classified according to the MedDRA classification. - For the non-interventional control group, the occurrence, intensity, duration of seizures during the 30 days after Visit Day 1 and Visit Month 1, classified according to the MedDRA classification.
5. Occurrence of generalised convulsive seizures (classified by Brighton classification) in subjects aged 1-11 and 12-17 years. - For vaccinated subjects, the occurrence of generalised convulsive seizures occurring within 7 days after each vaccination. - For the non-interventional control group, the occurrence of generalised convulsive seizures occurring within 7 days of Visit Day 1 and Visit Month 1.
6. Anti-gE antibody concentrations (geometric mean concentration) at Month 2 (one month post-dose 2) in each age category (1-11 and 12-17 years).

Secondary endpoints 9

1. Occurrence of SAEs, pIMDs and renal allograft rejection in subjects aged 1-11 and 12-17 years. - For vaccinated subj.,occurrence and relationship to vaccination of all SAEs, pIMDs and biopsy confirmed renal allograft rejection from VD1 up to VM13. - For non-interventional control group, occurrence of SAEs, pIMDs and biopsy confirmed renal allograft rejection from VD1 up to VM13.
2. Occurrence of HZ in subj aged 1-11 and 12-17 years. - For vaccinated subj, occurrence of HZ from VD1 until VM13. - For non-interventional control group, occurrence of HZ from VD1 until VM13.
3. Occurrence of solicited local AEs and gen. AEs/gen.symptoms in subj.aged 1-17 yrs: For vaccinated subj.(1-17 yrs),occurrence,intensity and duration of each solicited local AE within 7D after each vaccination. For vaccinated subj. (1-17 yrs),occurrence,intensity,duration and relationship to vaccination of each solicited gen. AE within 7D after each vacc. For non-interventional control group (1-17 yrs),occurrence,intensity and duration of each solicited gen. symptoms within 7D after VD1 and VM1.
4. Occurrence of unsolicited AEs/unsolicited symptoms in subjects aged 1-17 years. - For vaccinated subjects, the occurrence, intensity, duration and relationship to vaccination of unsolicited AEs during 30 days after each vaccination, classified according to MedDRA classification. - For the non-interventional control group, the occurrence intensity and duration of unsolicited symptoms during 30 days after Visit Day 1 and Visit Month 1 classified according to MedDRA classification.
5. Occurrence of SAEs, pIMDs and renal allograft rejection in subjects aged 1-17 years: For vaccinated subj, occurrence and relationship to vaccination of all SAEs, pIMDs and biopsy-confirmed renal allograft rejection from VD1 until VM2 & from VD1 to VM13 For non-interventional control group, occurrence of all SAEs, pIMDs and biopsy-confirmed renal allograft rejection from VD1 until VM2 & from VD1 until VM13.
6. Occurrence of HZ in subjects 1-17 years. - For vaccinated subjects the occurrence of HZ from Visit Day 1 until Visit Month 13. - For the non-interventional control group, the occurrence of HZ from Visit Day 1 until Visit Month 13.
7. Occurrence of seizures in subjects 1-17 years. - For vaccinated subjects, the occurrence, intensity, duration and relationship to vaccination of seizures during the 30 days after each vaccination, classified according to the MedDRA classification. - For the non-interventional control group, the occurrence, intensity and duration of unsolicited symptoms during the 30 days after Visit Day 1 and Visit Month 1 classified according to the MedDRA classification.
8. Occurrence of generalised convulsive seizures (according to Brighton classification) in subjects aged 1-17 years. - For vaccinated subjects, the occurrence and relationship of generalised convulsive seizures occurring within 7 days after each vaccination. - For non-interventional control group, the occurrence of generalised convulsive seizures occurring within 7 days following Visit Day 1 and Visit Month 1.
9. VRR for anti-gE humoral immunogenicity at M2 and M13 for subj in each age category (1-11 and 12-17 years) and in the combined age category (1-17 years). - Median fold increase for anti gE antibodies at M2 and M13 for subj in each age category (1-11 and 12-17 y) - Anti-gE antibody concentrations (GMCs) at D1 (pre-vacc) and M13 in each age category (1-11 and 12-17 y) - Anti-gE antibody concentrations (GMCs and median fold increase) at D1,M2 and M13 in pooled age category (1-17 y)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GlaxoSmithKline Biologicals

Sponsor organisation

GlaxoSmithKline Biologicals

Address

Rue De L'institut 89

City

Rixensart

Postcode

1330

Country

Belgium

Scientific contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

EU GSK Clinical Trials Call Center

Third parties 5

Locations

6 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 111 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications