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

NCT02058589 | Completed Phase 3 Results

• 2 other identifiers: 1168862012-005059-18
• Study Type: interventional
• Target: 265
• Locations: 9 countries
• Sites: 34

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.

Conditions

Herpes Zoster

Keywords

Immunocompromised; Safety; ≥ 18 years of age; Renal transplant; Adults; Immunosuppressed; Immunogenicity; Herpes zoster

Outcome Measures

Primary Outcomes (10)

• Number of Subjects With a Vaccine Response for Anti-glycoprotein E (gE) Humoral Immunogenicity

  Vaccine response was defined as: For initially seronegative subjects, antibody concentration at post-vaccination greater than or equal to (≥) 4 fold the cut-off for Anti-gE (4x97 milli-international units per milliliter \[mIU/ml\]); For initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration. Vaccine response was determined by Enzyme-Linked ImmunoSorbent Assay (ELISA).

  At Month 2.

• Number of Subjects With Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = Pain when limb was moved, which prevented everyday activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

  Within 7 days (Days 0-6) after each dose and across doses.

• Days With Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling.

  Within 7 days (Days 0-6) after each dose and overall/dose

• Number of Subjects With Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\] . Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Gastrointestinal symptoms (Gastro. sympt.) included nausea, vomiting, diarrhoea and/or abdominal pain.

  Within 7 days (Days 0-6) after each dose and across doses

• Days With Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\].

  Within 7 days (Days 0-6) after each dose and overall/dose

• Number of Subjects With Unsolicited Symptoms (AEs)

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  During the 30-day (Days 0-29) post-vaccination period

• Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)

  pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology

  From first vaccination (Month 0) up to 1 month post last vaccination (Month 2).

• Number of Subjects With Any and Related Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongatoion of hospitalization, or result in disability /incapacity. Related = SAE assessed by the investigator as related to the vaccination.

  From first vaccination (Month 0) up to 1 month post last vaccination (Month 2).

• Number of Subjects With Renal Allograft Rejection

  Renal allograft rejection was confirmed through biopsy.

  From the first vaccination (Month 0) up to 1 month post last vaccination (Month 2).

• Number of Subjects With Changes in Allograft Function

  Allograft function was indicated by the increase in levels of serum creatinine (≥ 1.20, ≥ 1.50, ≥ 1.75 or ≥ 2 fold increase). The number of subjects with declining allograft function, as determined by serum creatinine measurements post-vaccination (up to 30 days post-last vaccination) compared to pre-vaccination were presented.

  From the first vaccination (Month 0) up to 1 month post last vaccination (Month 2).

Secondary Outcomes (8)

• Anti-gE Antibody Concentrations

  At Months 0, 1, 2, 7 and 13

• Number of Subjects With a Vaccine Response for Anti-gE Humoral Immunogenicity

  At Months 1, 7 and 13

• Frequencies of gE-specific Cluster of Differentiation 4 (CD4+) T-cells

  At Months 0, 2 and 13

• Number of Subjects With a Vaccine Response for gE-specific CD4+ T-cells

  At Months 2 and 13

• Number of Subjects With Any and Related SAEs

  From 1 month post last vaccination (Month 2) until study end (Month 13).

Study Arms (2)

GSK1437173A Group

EXPERIMENTAL

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.

Biological: Herpes Zoster vaccine GSK1437173A

Placebo Group

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Herpes Zoster vaccine GSK1437173A BIOLOGICAL

2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.

GSK1437173A Group

Placebo DRUG

2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (34)

GSK Investigational Site

Brussels, 1090, Belgium

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5B 1W8, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Hradec Králové, 536 00, Czechia

Location

GSK Investigational Site

Helsinki, 00029, Finland

Location

GSK Investigational Site

Parma, Emilia-Romagna, 43126, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Siena, Tuscany, 53100, Italy

Location

GSK Investigational Site

Treviso, Veneto, 31100, Italy

Location

GSK Investigational Site

Panama City, Panama

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

GSK Investigational Site

Barakaldo (Vizcaya), 48903, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Córdoba, 14004, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Kaohsiung City, 833, Taiwan

Location

GSK Investigational Site

Keelung, 204, Taiwan

Location

GSK Investigational Site

Taichung, 407, Taiwan

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 30843046 DERIVED

MeSH Terms

Conditions

Herpes Zoster

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 10, 2014
• Study Start: March 20, 2014
• Primary Completion: May 11, 2016
• Study Completion: April 13, 2017
• Last Updated: August 1, 2018
• Results First Posted: August 1, 2018

Record last verified: 2018-06

Locations

CA (4); TW (5); FI (1); KR (2); ES (11); CZ (1); IT (5); PA (1); BE (4)