Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ/su) Vaccine in Adults With Solid Tumours Receiving Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' HZ/su vaccine in adults with solid tumours undergoing chemotherapy.

Detailed Description
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The study will be randomised into two groups based on the vaccination schedule in relation to the start of a chemotherapy cycle: The OnChemo group receives their first HZ/su vaccination at the start of a chemotherapy cycle, The PreChemo group receives their first HZ/su vaccination at least 10 days before the start of a chemotherapy cycle. The protocol summary has been updated following Protocol Amendment 2, August 2014, leading to the increase of the enrolment.

Official Title
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An Observer-blind Study to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults 18 Years of Age or Older With Solid Tumours Receiving Chemotherapy

Conditions
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Herpes Zoster, Herpes Zoster Vaccine

Intervention / Treatment
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* Biological: GSK 1437173A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. A male or female aged 18 years or older (and has reached the age of legal consent) at the time of study entry (i.e., when informed consent is signed). Subject who has been diagnosed with one or more solid tumours (defined as a solid malignancy, i.e., not a blood element malignancy). Subject who is receiving or will receive a cytotoxic or immunosuppressive chemotherapy (such that the study vaccine can be administered at the latest at the start of the second cycle of chemotherapy). Life expectancy of greater than one year. Female subjects of non-childbearing potential may be enrolled in the study: Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause; 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 vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Subjects receiving only newer, more targeted therapies if not taken together with a classical chemotherapy. Chronic administration and/or planned administration of systemic glucocorticoids within one month prior to the first vaccine dose and up to Visit 3 (Month 2). Inhaled, intra-articularly injected, and topical steroids are allowed. Previous vaccination against HZ or varicella within 12 months preceding the first dose of study vaccine/ placebo. Planned administration during the study of a HZ vaccine (including an investigational or non-registered vaccine) other than the study vaccine. Previous chemotherapy course less than one month before first study vaccination. Occurrence of a varicella or HZ episode by clinical history within the 12 months preceding the first dose of study vaccine/ placebo. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or study material and equipment. Administration or planned administration of a live vaccine in the period starting 30 days before 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. HIV infection by clinical history. Acute disease and/or fever at the time of vaccination. Acute disease is defined as the presence of a moderate or severe illness with or without fever, but excludes the underlying malignancy, as well as the expected symptoms/signs associated with that disease or its treatment: Fever is defined as temperature ≥ 37.5°C /99.5°F on oral, axillary or tympanic setting, or ≥ 38.0°C /100.4°F on rectal setting. 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 receive the first dose of study vaccine/ placebo at the discretion of the investigator. Any condition which, in the judgment of the investigator would make intramuscular injection unsafe. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 3 (i.e., 2 months after the last dose of study vaccine/ placebo).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1437173A Group<br>Subjects received the first dose of GSK 1437173A at least 10 days (up to 1 month) before start of chemotherapy cycle or at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of GSK 1437173A vaccine was administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy. The study products were administered intramuscularly into a deltoid muscle. The choice of and use of chemotherapy, or any other medication related to the patients' current conditions, were based on the local standard of care for the patients. | Biological: GSK 1437173A<br>* 2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.<br>* Other names: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine;|
| Placebo Comparator: Placebo Group<br>Subjects received the first dose of placebo at least 10 days (up to 1 month) before start of chemotherapy cycle or at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of placebo was administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy. The study products were administered intramuscularly into a deltoid muscle. The choice of and use of chemotherapy, or any other medication related to the patients' current conditions, were based on the local standard of care for the patients. | Drug: Placebo<br>* 2 doses administered by IM injection into the deltoid muscle of the non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Geometric Means for Anti-glycoprotein E (gE) Antibodies in PreChemo Groups | Adjusted geometric means (GMC) of GSK1437173A over placebo for anti-glycoprotein E (gE) antibody enzyme-linked immunosorbent assay (ELISA) concentrations in PreChemo Groups only. | At Month 2 | 
| Anti-Varicella Zoster Virus (VZV) gE Antibody Concentrations | Antibody concentrations as determined by ELISA are presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (≥) 97 mIU//mL. | At Month 2 | 
| Number of Subjects With Any and Grade 3 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 that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Days With Solicited Local Symptoms | The number of days with any local symptoms has been assessed during the post-vaccination period. | During the 7-day (Days 0-6) post-vaccination period following each dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal [symptoms included nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, shivering and fever [defined as oral, axillary or tympanic 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. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Days With Solicited General Symptoms | The number of days with any general symptoms has been assessed during the post-vaccination period. | During the 7-day (Days 0-6) post-vaccination period following each dose | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (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 Serious Adverse Events (SAEs) | Serious adverse events (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= SAE assessed by the investigator as causally related to the study vaccination. | From first dose up to 30 days post last vaccination | 
| Number of Subjects With Any and Related Potential Immune Mediated Diseases (pIMDs) | Potential immune-mediated diseases (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. Related = pIMDs assessed by the investigator as causally related to the study vaccination. | From first vaccination up to 30 days post last vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-VZV gE Antibody Concentrations | Antibody concentrations as determined by ELISA are presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (≥) 97 mIU//mL. | At Months 0, 1, 6 and 13 | 
| Number of Subjects With Vaccine Responses for Anti-gE Antibody ELISA Concentrations | Vaccine response defined as: For initially seronegative subjects, antibody concentration at post-vaccination ≥ 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. | At Months 1, 2, 6 and 13 | 
| Descriptive Statistics of the Frequency of gE-specific CD4[2+] T-cells in PreChemo Groups | Descriptive statistics were tabulated for CD4[2+] cells, which are gE specific CD4+ T-cells with at least two activation markers ([2+]), expressed from the activation markers interferon-gamma (IFN-γ), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40-ligand (CD40-L), as determined by intracellular cytokine staining (ICS) method. | At Months 0, 1, 2 and 13 | 
| Number of Subjects With Vaccine Responses for gE-specific CD4[2+] T-cells in PreChemo Groups | Vaccine response defined as: For initially seronegative subjects with pre-vaccination T-cell frequencies below the threshold, at least a 2-fold increase as compared to the threshold (2x320 Events/10E6 CD4+ T cells); For initially seropositive subjects with pre-vaccination T-cell frequencies above the threshold, at least a 2-fold increase as compared to pre-vaccination T-cell frequencies. | At Months 1, 2 and 13 | 
| Number of Subjects With Serious Adverse Events (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 = SAE assessed by the investigator as causally related to the study vaccination. | From 30 days post last vaccination up to study end (Month 13) | 
| Number of Subjects With Any Potential Immune Mediated Diseases (pIMDs) | Potential immune-mediated diseases (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 30 days post last vaccination up to study end (Month 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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≥18 years of age, Chemotherapy, Solid tumours, Immunogenicity, Herpes Zoster, Safety, Shingles