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Herpes ZosterPhase 3NCT02058589

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

A Phase 3 study testing Herpes Zoster vaccine GSK1437173A in people with Herpes Zoster, run by GlaxoSmithKline at 34 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Herpes Zoster
What is being tested?
Herpes Zoster vaccine GSK1437173A
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
265 participants
Where
34 sitesin 9 countries
Study dates
20 Mar 2014to 13 Apr 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 16Show fewer
  • 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.

Who cannot join

  • 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).
Show all 28Show fewer
  • 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 locations and contacts

34 sites in 9 countries.

34 sites in 9 countries

Spain11 sites
  • GSK Investigational Site

    Barakaldo (Vizcaya), 48903

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Córdoba, 14004

  • GSK Investigational Site

    L'Hospitalet de Llobregat, 08907

  • GSK Investigational Site

    Madrid, 28007

  • GSK Investigational Site

    Madrid, 28034

  • GSK Investigational Site

    Madrid, 28040

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Santander, 39008

  • GSK Investigational Site

    Seville, 41013

Other trials in Spain

Italy5 sites
  • GSK Investigational Site

    Genoa, Liguria, 16132

  • GSK Investigational Site

    Milan, Lombardy, 20132

  • GSK Investigational Site

    Parma, Emilia-Romagna, 43126

  • GSK Investigational Site

    Siena, Tuscany, 53100

  • GSK Investigational Site

    Treviso, Veneto, 31100

Other trials in Italy

Taiwan5 sites
  • GSK Investigational Site

    Kaohsiung City, 833

  • GSK Investigational Site

    Keelung, 204

  • GSK Investigational Site

    Taichung, 407

  • GSK Investigational Site

    Taipei, 100

  • GSK Investigational Site

    Taoyuan, 333

Other trials in Taiwan

Belgium4 sites
  • GSK Investigational Site

    Brussels, 1090

  • GSK Investigational Site

    Brussels, 1200

  • GSK Investigational Site

    Ghent, 9000

  • GSK Investigational Site

    Leuven, 3000

Other trials in Belgium

Canada4 sites
  • GSK Investigational Site

    Edmonton, Alberta, T6G 2B7

  • GSK Investigational Site

    Halifax, Nova Scotia, B3K 6R8

  • GSK Investigational Site

    Toronto, Ontario, M5B 1W8

  • GSK Investigational Site

    Toronto, Ontario, M5G 2N2

Other trials in Canada

South Korea2 sites
  • GSK Investigational Site

    Seoul, 135-710

  • GSK Investigational Site

    Seoul, 137-701

Other trials in South Korea

Czechia1 site
  • GSK Investigational Site

    Hradec Králové, 536 00

Other trials in Czechia

Finland1 site
  • GSK Investigational Site

    Helsinki, 00029

Other trials in Finland

Panama1 site
  • GSK Investigational Site

    Panama City

Other trials in Panama

About this study

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

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
Being tested
Herpes Zoster vaccine GSK1437173A, Placebo
Keywords
Immunocompromised, Safety, ≥ 18 years of age, Renal transplant, Adults, Immunosuppressed, Immunogenicity, Herpes zoster
Medical subject headings
Herpes Zoster

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Herpes Zoster vaccine GSK1437173ABiological

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

  • PlaceboDrug

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

Study groups in NCT02058589
Study groupRoleWhat they receive
GSK1437173A GroupExperimentalSubjects, 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.
Receives: Biological: Herpes Zoster vaccine GSK1437173A
Placebo GroupPlacebo comparatorSubjects, 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: At Month 2.

  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.

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

  3. Days With Solicited Local Symptoms

    Assessed solicited local symptoms were pain, redness and swelling.

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

  4. 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.

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

  5. 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)].

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

  6. 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.

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

  7. 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

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

  8. 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.

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

  9. Number of Subjects With Renal Allograft Rejection

    Renal allograft rejection was confirmed through biopsy.

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

  10. 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.

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

Secondary outcomes (8)
  1. Anti-gE Antibody Concentrations

    Varicella Zoster Virus (VZV) gE antibody Immunoglobulin G concentrations were determined by ELISA assay, presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The reference seropositivity cut-off value was ≥ 97 mIU/mL.

    Measured: At Months 0, 1, 2, 7 and 13

  2. Number of Subjects With a Vaccine Response for Anti-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 mIU/mL); For initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration. Vaccine response was determined by ELISA.

    Measured: At Months 1, 7 and 13

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

    Descriptive statistics of gE-specific CD4+ T-cells, expressing at least two activation markers (from among interferon gamma [IFN-γ], interleukin-2 [IL-2], tumour necrosis factor alpha [TNF-α] and cluster of differentiation 40-ligand [CD40L]) were tabulated, as determined by in vitro Intracellular Cytokine Staining (ICS).

    Measured: At Months 0, 2 and 13

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

    Vaccine response for gE-specific CD4+ T-cells expressing at least two activation markers (from among IFN-γ, IL-2, TNF-α and CD40L), was determined by in vitro ICS. Vaccine response was defined as: For initially subjects with pre-vaccination T-cell frequencies below the threshold, at least a 2-fold increase as compared to the threshold (2x<320> Events/10 million CD4+ T-cells); For initially subjects with pre-vaccination T-cell frequencies above the threshold, at least a 2-fold increase as compared to pre-vaccination T-cell frequencies.

    Measured: At Months 2 and 13

  5. Number of Subjects With Any and Related SAEs

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

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

  6. Number of Subjects With Any 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.

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

  7. Number of Subjects With Renal Allograft Rejection

    Renal allograft rejection was confirmed through biopsy.

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

  8. 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 (from 30 days post-last vaccination up to study end) compared to pre-vaccination were presented.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2014 (estimated)
  2. Study start20 Mar 2014
  3. Primary completion11 May 2016
  4. Study completion13 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
265 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02058589
Sponsor's protocol ID
116886
Other IDs
2012-005059-18
Status last verified
Jun 2018
First submitted
6 Feb 2014
Last updated
1 Aug 2018
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 30843046

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Herpes Zoster vaccine GSK1437173A in people with Herpes Zoster, run by GlaxoSmithKline at 34 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Spain, Italy, Taiwan, Belgium, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With a Vaccine Response for Anti-glycoprotein E (gE) Humoral Immunogenicity (time frame: At Month 2.). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02058589, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2018.

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