Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine in Adults 18 Years of Age or Older With Renal Transplant

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Herpes Zoster

Treatments: Biological: Herpes Zoster vaccine GSK1437173A; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02058589

2012-005059-18 (EudraCT Number)

116886

Details and patient eligibility

About

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.

Enrollment: 265 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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265 participants in 2 patient groups, including a placebo group

GSK1437173A Group

Experimental group

Description:

Subjects, aged 18 years or older, received 2 doses of the GSK 1437173A vaccine, adjuvanted with AS01B at Day 0, and Month 1, administered intramuscularly, in the deltoid muscle of an arm.

Treatment:

Biological: Herpes Zoster vaccine GSK1437173A

Placebo Group

Placebo Comparator group

Description:

Subjects, aged 18 years or older, received 2 doses of Placebo (lyophilised sucrose reconstituted with saline \[NaCl\] solution) at Day 0, and Month 1, administered intramuscularly, in the deltoid muscle of an arm.

Treatment:

Drug: Placebo