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Herpes Zoster

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Vaccines

Subjects will receive the candidate HZ vaccine (GSK 1437173A).

Subjects will receive the placebo vaccine.

2 doses administered intramuscularly (IM) in deltoid region of non-dominant arm. Dose 1 administered at Day 0. Dose 2 administered 1-2 months post Dose 1.

Herpes zoster vaccine (GSK 1437173A)

Placebo

GSK Clinical Trials

The purpose of this study is to evaluate the safety and immunogenicity of GSK Biologicals' vaccine GSK1437173A in subjects aged 18 years and older with blood cancers. The study will evaluate safety-related events and antibody and cellular immune responses to the study vaccine, as compared to placebo.

Amendment to protocol posting:

Increase in sample size, update of country/region-specific information (Sections 5, 6 and 9).

Promotion of secondary to primary objective; related update of primary and secondary outcome measures (Sections 4 and 7).

Study to Assess the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine in Adults Aged 18 Years and Older With Blood Cancers

Study to Evaluate Safety and Immunogenicity of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults Aged 18 Years and Older With Haematologic Malignancies

Vaccine response rate refers to the percentage of subjects with a vaccine response, as determined by Enzyme-Linked Immunosorbent Assay (ELISA). Vaccine response was defined as: For initially seronegative subjects, antibody concentration at Month 2 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 Month 2 ≥ 4 fold the pre-vaccination antibody concentration.

This analysis was performed on subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.

The Adjusted geometric mean concentration was measured in all subjects excluding those with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.

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 activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

Solicited local symptoms: pain, redness, swelling and their number of days were recorded after each vaccination dose.

Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia, shivering and fever \[defined as oral, axillary or tympanic route measured temperature equal to or above 37.5 degrees Celsius (°C)\]. 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.

Solicited general symptoms: fatigue, gastrointestinal symptoms, headache, myalgia, shivering, temperature and their number of days were recorded after each vaccination dose.

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. It also included 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.

A Serious adverse event (SAE) is any untoward medical occurrence that result in death, is life threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject. Related = SAEs assessed by the investigator as causally related to the study vaccination

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

Vaccine response rate refers to the percentage of subjects with a vaccine response, as determined by ELISA. Vaccine response was defined as: For initially seronegative subjects, antibody concentration at Month 2 ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/mL). For initially seropositive subjects, antibody concentration at Month 2 ≥ 4 fold the pre -vaccination antibody concentration. This analysis was performed on subjects with haematologic malignancies, excluding subjects with Non-Hodgkin B-cell Lymphoma.

Antibody concentrations were determined by ELISA, presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).This parameter was assessed in subjects with haematologic malignancies, excluding subjects with Non-Hodgkin B-cell Lymphoma.

Time to occurrence of any confirmed HZ case is expressed in terms of incidence rate of subjects with at least one event. Hence, person-year rate = number of episodes (n)/ sum of follow-up period (censored at the first occurrence of an event) expressed in years (T\[year)\]). Follow-up period starts Day 1 of vaccination.

Any clinically suspected case of HZ (defined as (1) a new rash characteristic of HZ (e.g., unilateral, dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or other sensations), or a vesicular rash suggestive of Varicella Zoster Virus (VZV) infection regardless of the distribution, and no alternative diagnosis; or (2) a clinical presentation (symptoms and/or signs) and specific laboratory findings suggestive of VZV infection in the absence of characteristic HZ or VZV rash.) The endpoint is confirmed in two ways: (1) By Polymerase Chain Reaction (PCR) or (2) By the HZ Ascertainment Committee. The PCR is used as primary classification method.

Antibody concentrations were determined by ELISA, presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). This parameter was assessed in all vaccinated subjects.

Vaccine response rate refers to the percentage of subjects with a vaccine response, as determined by ELISA. Vaccine response was defined as: For initially seronegative subjects, antibody concentration at Month 2 ≥ 4 fold the cut-off for anti-gE (4x97 mIU/mL). For initially seropositive subjects, antibody concentration at Month 2 ≥ 4 fold the pre -vaccination antibody concentration. Vaccine response was measured in all subjects.

Among markers expressed were interferon-gamma (IFN-γ), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L), as determined by in vitro intracellular cytokine staining (ICS).

Among markers expressed were IFN-γ, IL-2, TNF-α and CD40L, as 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/106 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.

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

GMCs of anti-gE antibodies were tabulated per study group and HZ confirmed/non-confirmed status and expressed in milli-international units per milliliter (mIU/mL).

MGI was tabulated per study group and HZ confirmed/non-confirmed status. MGI was defined as the Geometric mean of the within subject ratios of the post-vaccination reciprocal anti-gE concentration to the Month 0 reciprocal anti-gE concentration.

GlaxoSmithKline

Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).

GSK1437173A Group

Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).

Placebo Group

Total

Age, Continuous

Sex: Female, Male

Geographic ancestry

Race/Ethnicity, Customized

GSK Response Center

Subjects who received placebo doses according to a 0, 1 Months schedule. (The second dose of placebo could be administered 1 - 2 months after the first dose).

The analysis was performed on the According-to-Protocol (ATP) cohort for Humoral immunogenicity, which included all subjects who met all eligibility criteria, who received the full vaccination course, complied with the protocol and and for whom data concerning immunogenicity outcome measures were available up to the Month 2 visit.

Vaccine Response Rates (VRR) for Anti-glycoprotein E (Anti-gE) Antibody Concentrations

The objective aimed to evaluate anti-gE humoral immune responses at Month 2 following a two-dose administration of the GSK1437173A vaccine, as compared to placebo, in subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.

The analysis was performed on the According-to-Protocol (ATP) cohort for Humoral immunogenicity, which included all subjects who met all eligibility criteria, who received the full vaccination course, complied with the protocol and for whom data concerning immunogenicity outcome measures were available up to the Month 2 visit.

Adjusted Geometric Mean Concentration of Anti-gE Antibodies

Any Pain, Dose 1

Grade 3 Pain, Dose 1

Any Redness, Dose 1

Grade 3 Redness, Dose 1

Any Swelling, Dose 1

Grade 3 Swelling, Dose 1

Any Pain, Dose 2

Grade 3 Pain, Dose 2

Any Redness, Dose 2

Grade 3 Redness, Dose 2

Any Swelling, Dose 2

Grade 3 Swelling, Dose 2

Any Pain, Across doses

Grade 3 Pain, Across doses

Any Redness, Across doses

Grade 3 Redness, Across doses

Any Swelling, Across doses

Grade 3 Swelling, Across doses

The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administered, who had their symptom sheets completed.

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Pain, Dose 1

Pain, Dose 2

Redness, Dose 1

Redness, Dose 2

Swelling, Dose 1

Swelling, Dose 2

Number of Days With Solicited Local Symptoms

Any fatigue, Dose 1

Grade 3 fatigue, Dose 1

Related fatigue, Dose 1

Any gastrointestinal, Dose 1

Grade 3 gastrointestinal, Dose 1

Related gastrointestinal, Dose 1

Any headache, Dose 1

Grade 3 headache, Dose 1

Related headache, Dose 1

Any myalgia, Dose 1

Grade 3 myalgia, Dose 1

Related myalgia, Dose 1

Any shivering, Dose 1

Grade 3 shivering, Dose 1

Related shivering, Dose 1

Any temperature, Dose 1

Grade 3 temperature, Dose 1

Related temperature, Dose 1

Any fatigue, Dose 2

Grade 3 fatigue, Dose 2

Related fatigue, Dose 2

Any gastrointestinal, Dose 2

Grade 3 gastrointestinal, Dose 2

Related gastrointestinal, Dose 2

Any headache, Dose 2

Grade 3 headache, Dose 2

Related headache, Dose 2

Any myalgia, Dose 2

Grade 3 myalgia, Dose 2

Related myalgia, Dose 2

Any shivering, Dose 2

Grade 3 shivering, Dose 2

Related shivering, Dose 2

Any temperature, Dose 2

Grade 3 teamperature, Dose 2

Related temperature, Dose 2

Any fatigue, Across doses

Grade 3 fatigue, Across doses

Related fatigue, Across doses

Any gastrointestinal, Across doses

Grade 3 gastrointestinal, Across doses

Related gastrointestinal, Across doses

Any headache, Across doses

Grade 3 headache, Across doses

Related headache, Across doses

Any myalgia, Across doses

Grade 3 myalgia, Across doses

Related myalgia, Across doses

Any shivering, Across doses

Grade 3 shivering, Across doses

Related shivering, Across doses

Any temperature, Across doses

Grade 3 temperature, Across doses

Related teamperature, Across doses

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Fatigue, Dose 1

Fatigue, Dose 2

Gastrointestinal symptoms, Dose 1

Gastrointestinal symptoms, Dose 2

Headache, Dose 1

Headache, Dose 2

Myalgia, Dose 1

Myalgia, Dose 2

Shivering, Dose 1

Shivering, Dose 2

Temperature, Dose 1

Temperature, Dose 2

Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose)

Subjects who received placebo doses according to a 0, 1 Months schedule. (The second dose of placebo could be administered 1 - 2 months after the first dose)

Number of Days With Solicited General Symptoms

Any AEs

Grade 3 AEs

Related AEs

The analysis was performed on the Total Vaccinated cohort, which included all all subjects with at least one vaccine dose administered.

Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)

At least one SAE

Related SAEs

The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administered.

Number of Subjects With Serious Adverse Events (SAEs)

Any pIMDs

Related pIMDs

Number of Subjects Reporting Any and Related Potential Immune-mediated Diseases (pIMDs)

The analysis was performed on the According-to-Protocol (ATP) cohort for Humoral immunogenicity, which included all subjects who met all eligibility criteria, received the full vaccination course, complied with the protocol and for whom data concerning immunogenicity outcome measures were available up to the Month 2 visit.

Vaccine Response Rate (VRR) for Anti-gE Antibody Concentrations

Anti-gE Antibody Concentrations

Time to Occurrence of Any Confirmed HZ Case

Anti-gE, Month 0

Anti-gE, Month 1

Anti-gE, Month 2

Anti-gE, Month 13

The analysis was performed on the adapted ATP cohort for Humoral immunogenicity, which included all subjects who met all eligibility criteria, received the full vaccination course, complied with the protocol and for whom data concerning immunogenicity outcome measures were available up to the Month 13 visit.

VRR, anti-gE, Month 1

VRR, anti-gE, Month 2

VRR, anti-gE, Month 13

CD4 [2+], Month 0

CD4 [2+], Month 1

CD4 [2+], Month 2

CD4 [2+], Month 13

The analysis was performed on the adapted ATP cohort for Cell-Mediated Immunogenicity (CMI), which included all evaluable subjects included in the ATP cohort for Humoral immunogenicity analyses and included in the CMI sub-cohort.

Frequency of gE -Specific Cluster of Differentiation 4 (CD4) [2+] T-cells Expressing at Least 2 Activation Markers

The analysis was performed on the adapted ATP cohort for Cell Mediated Immunity (CMI), which included all evaluable subjects included in the ATP cohort for Humoral immunogenicity analyses and included in the CMI sub-cohort.

Vaccine Response Rates (VRR) for gE-specific CD4 [2+] T-cells, Expressing at Least 2 Activation Markers

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study to Assess the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine in Adults Aged 18 Years and Older With Blood Cancers	NCT01767467	Herpes Zoster	Herpes zoster v... Placebo	18 Years -	GlaxoSmithKline
Study to Assess the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine in Adults Aged 18 Years and Older With Blood Cancers	NCT01767467	Herpes Zoster	Herpes zoster v... Placebo	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for herpes zoster vaccine (gsk 1437173a)