Clinical trial NCT02058589: Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine in Adults 18 Years of Age or Older With Renal Transplant
Official title: Observer-blind Study to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A in Adults 18 Years of Age or Older With Renal Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Zoster
Keywords: Immunocompromised
Safety
≥ 18 years of age
Renal transplant
Adults
Immunosuppressed
Immunogenicity
Herpes zoster
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-02-10
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' HZ/su vaccine administered on a 0- and 1- to 2-months schedule in adults 18 years of age or older who are receiving chronic immunosuppressive therapy.


Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* A male or female, aged 18 years or older and having reached the age of legal consent, on the date the informed consent is signed.
* Written informed consent obtained from the subject.
* Subject who has received an ABO compatible allogeneic renal transplant.
* Subject receiving maintenance immunosuppressive therapy for the prevention of allograft rejection for a minimum of one month (30 days) prior to the first vaccination.
* Subject without an episode of allograft rejection over the previous three months (90 days) prior to the first vaccination.
* Subject with stable renal function, stability defined as:

  * less than 20% variability between last two creatinine measurements or calculated GFR
  * or in the opinion of the investigator after investigator review of more than the last two creatinine measurements or calculated GFRs.
* Subject not less than 4 months (120 days) and not more than 18 months (547 days) after allograft transplantation at the time of the first vaccination.
* Subjects with multiple dialysis options (peritoneal and/or more than one anatomical access site for haemodialysis) in the event acute or chronic dialysis is needed.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of the first vaccination, and
  * has agreed to continue adequate contraception during the primary treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Any primary kidney disease with a high incidence of recurrent primary kidney disease.
* Evidence of recurrent primary kidney disease within the current allograft.
* Previous allograft loss secondary to recurrent primary kidney disease.

  * Multiple kidney transplants are allowed if the reason for a previous allograft's loss is not recurrent primary kidney disease.
* More than one organ transplanted (i.e. kidney-liver, double kidney or kidney-other organ(s) transplanted).
* History of events that, in the opinion of the investigator, may put subject at increased risk for chronic allograft dysfunction (e.g. delayed graft function, peri-operative complications).
* Histologic reports of chronic allograft injury (e.g. transplant glomerulopathy, arteriopathy, C4d deposition).
* Evidence of significant proteinuria in the opinion of the investigator.
* Panel reactive antibody score (PRA or cPRA) that is unknown at the time of transplant.
* Any autoimmune or potential immune-mediated disease including primary kidney disease.
* Use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab) as induction, maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months (274 days) of first dose of study vaccine/placebo.
* Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/placebo, or planned use during the study period.
* Concurrent or planned participation in another clinical study, at any time during the study period, which has exposed or will expose the subject to an investigational or a non-registered product
* Administration or planned administration of a live vaccine within 30 days prior to the first dose of study vaccine and ending 30 days after the last dose of study vaccine, or, administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.
* Planned administration during the study of a varicella or HZ vaccine other than the study vaccine.
* Previous vaccination against HZ or varicella within the 12 months preceding the first dose of study vaccine/placebo.
* Occurrence of varicella or HZ per clinical history, within the 12 months preceding the first dose of study vaccine/placebo.
* Failure to fully complete the 7-day pre-vaccination diary card distributed at the Pre-vaccination visit.
* Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of induction and/or maintenance immunosuppressive therapies.
* Any confirmed or suspected HIV, primary immunodeficiency disease, disseminated or untreated malignancy, or systemic infection.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study material and equipment.
* Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe.
* Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
* Acute disease and/or fever at the time of vaccination.

  * Fever is defined as temperature ≥ 37.5°C /99.5°F by oral route. The preferred route for recording temperature in this study will be oral.
  * Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 3.

Primary outcomes:
measure: Number of Subjects With a Vaccine Response for Anti-glycoprotein E (gE) Humoral Immunogenicity
timeFrame: At Month 2.
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after each dose and across doses.
measure: Days With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after each dose and overall/dose
measure: Number of Subjects With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after each dose and across doses
measure: Days With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after each dose and overall/dose
measure: Number of Subjects With Unsolicited Symptoms (AEs)
timeFrame: During the 30-day (Days 0-29) post-vaccination period
measure: Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: From first vaccination (Month 0) up to 1 month post last vaccination (Month 2).
measure: Number of Subjects With Any and Related Serious Adverse Events (SAEs)
timeFrame: From first vaccination (Month 0) up to 1 month post last vaccination (Month 2).
measure: Number of Subjects With Renal Allograft Rejection
timeFrame: From the first vaccination (Month 0) up to 1 month post last vaccination (Month 2).
measure: Number of Subjects With Changes in Allograft Function
timeFrame: From the first vaccination (Month 0) up to 1 month post last vaccination (Month 2).
Secondary outcomes:
measure: Anti-gE Antibody Concentrations
timeFrame: At Months 0, 1, 2, 7 and 13
measure: Number of Subjects With a Vaccine Response for Anti-gE Humoral Immunogenicity
timeFrame: At Months 1, 7 and 13
measure: Frequencies of gE-specific Cluster of Differentiation 4 (CD4+) T-cells
timeFrame: At Months 0, 2 and 13
measure: Number of Subjects With a Vaccine Response for gE-specific CD4+ T-cells
timeFrame: At Months 2 and 13
measure: Number of Subjects With Any and Related SAEs
timeFrame: From 1 month post last vaccination (Month 2) until study end (Month 13).
measure: Number of Subjects With Any pIMDs
timeFrame: From 1 month post last vaccination (Month 2) until study end (Month 13).
measure: Number of Subjects With Renal Allograft Rejection
timeFrame: From 1 month post last vaccination (Month 2) until study end (Month 13).
measure: Number of Subjects With Changes in Allograft Function
timeFrame: From 1 month post last vaccination (Month 2) until study end (Month 13)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: GSK Investigational Site
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: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Parma
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Siena
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Treviso
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Barakaldo (Vizcaya)
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Hospitalet de Llobregat
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Keelung
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Vink P, Ramon Torrell JM, Sanchez Fructuoso A, Kim SJ, Kim SI, Zaltzman J, Ortiz F, Campistol Plana JM, Fernandez Rodriguez AM, Rebollo Rodrigo H, Campins Marti M, Perez R, Gonzalez Roncero FM, Kumar D, Chiang YJ, Doucette K, Pipeleers L, Aguera Morales ML, Rodriguez-Ferrero ML, Secchi A, McNeil SA, Campora L, Di Paolo E, El Idrissi M, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L; Z-041 Study Group. Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis. 2020 Jan 2;70(2):181-190. doi: 10.1093/cid/ciz177.