Study to Assess the Immunogenicity and Safety of GSK's Investigational Vaccine (GSK3277511A) When Given to Healthy Smokers and Ex-smokers After Administration of Shingrix Vaccine

Study Overview
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Brief Summary
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This study will provide information regarding the sequential administration of two vaccines adjuvanted with AS01. The aim of this study is to understand immunogenicity and safety of NTHi-Mcat vaccine when administered sequentially after Shingrix vaccine and to compare to the immunogenicity of NTHi-Mcat vaccine administered alone. This study will also provide information regarding whether a specific time period is required between the administration of these two different vaccines containing the same adjuvant- AS01 components. The population of this study will include healthy smokers and ex-smokers of 50 to 80 years of age which will be used as a proxy for the COPD population.

Official Title
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Immunogenicity and Safety Study of GSK's Investigational Vaccine (GSK3277511A) When Administered in Healthy Smokers and Ex-smokers Following Receipt of Shingrix Vaccine

Conditions
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Respiratory Disorders

Intervention / Treatment
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* Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E
* Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)


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 (e.g. completion of the diary cards, return for follow-up visits). Written informed consent obtained from the subject prior to performance of any study specific procedure. A male or female between, and including, 50 years and 80 years of age at the time of the first vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. Current or former smoker with a cigarette smoking history ≥10 pack-years. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral 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: Medical conditions Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of potential immune-mediated disease (pIMD). Note: If the subject has any condition on the list of pIMDs specified in the protocol, they must be excluded unless the aetiology is clearly documented to be non-immune mediated. The investigator will exercise his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin and thus meet the exclusion criteria. Diagnosis of COPD regardless of severity. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Additionally, consider allergic reactions to other material or equipment related to study participation (such as materials that may possibly contain latex -gloves, syringes, etc). Has significant disease (including significant psychological disorders), in the opinion of the investigator, likely to interfere with the study and/or likely to cause death within the study duration. History of or current condition preventing intramuscular injection as bleeding or coagulation disorder. Malignancies within previous 5 years (excluding non-melanoma skin cancer) or lymphoproliferative disorders. Prior/concomitant therapy Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine administration, with the exception of non-MF59 adjuvanted influenza vaccines and pneumococcal vaccines which may be administered ≥15 days preceding or following any study vaccine dose. Note: For M59 adjuvanted flu vaccine and for any vaccine containing novel adjuvant refer to exclusion criteria below. Planned administration/administration of a vaccine adjuvanted with the following adjuvants AS01, AS02, AS03, AS04 and MF59 in the period starting 6 months before the first dose of study vaccine, and ending at the second blood draw (i.e. approximately 1 month after the administration of the last dose of NTHi-Mcat vaccine). The following non-exhaustive list should be considered as criteria for exclusion: Prepandrix, Adjupanrix, Shingrix, Fendrix, Cervarix, FluAd, Chiromas, Gripguard. Previous vaccination with any vaccine containing NTHi and/or Mcat antigens Previous vaccination with Shingrix; (either registered product or participation in a previous vaccine study). Previous vaccination with HZ live-attenuated vaccine (ZVL)) (either registered product or participation in a previous vaccine study) within the 2 months of the first study visit (Day 1). Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose, and ending at the second blood draw. (i.e. approximately 1 month after the administration of the last dose of NTHi-Mcat vaccine). For corticosteroids, this will mean prednisone ≥5 mg/day (for adult subjects), or equivalent. Only topical steroids are allowed. Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine or planned administration starting from Day 1 and ending at the second blood draw (i.e. approximately 1 month after the planned administration of the second dose of NTHi-Mcat vaccine). Prior/concurrent clinical study experience Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device). Other exclusions: Pregnant or lactating female, Female planning to become pregnant or planning to discontinue contraceptive precautions, Current alcoholism and/or drug abuse, Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study Any study personnel or immediate dependents, family, or household member.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sh_NTHi-Mcat_1 Group<br>Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, and following a 1-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 91, and Day 151. | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E<br>* 2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm<br>Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)<br>* 2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh_NTHi-Mcat_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm<br>|
| Experimental: Sh_NTHi-Mcat_3 Group<br>Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 3-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 151 and Day 211. | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E<br>* 2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm<br>Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)<br>* 2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh_NTHi-Mcat_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm<br>|
| Experimental: Sh_NTHi-Mcat_6 Group<br>Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 6-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart at Day 241 and Day 301. | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E<br>* 2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm<br>Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)<br>* 2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh_NTHi-Mcat_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm<br>|
| Active Comparator: NTHi-Mcat Group<br>Subjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61. | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E<br>* 2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm<br>|
| Experimental: Shingrix-Only Group<br>Subjects belonging to this group were originally randomized to either Sh_NTHi-Mcat_1 Group, Sh_NTHi-Mcat_3 Group or Sh_NTHi-Mcat_6 Group, they received at least 1, maximum 2 doses of GSK Biologicals Shingrix vaccine at Day 1 and Day 61, but didnt receive any dose of NTHI Mcat investigational vaccine. Only safety data were collected for these subjects. | Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)<br>* 2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh_NTHi-Mcat_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Protein D (PD), Anti-Protein E (PE), Anti-type IV Pili Subunit (PilA) and Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Adjusted Geometric Mean Concentrations (GMCs), One-month Post Dose-2 of NTHi-Mcat Vaccine | Antibody concentrations as measured by ELISA (Enzyme-linked immunosorbent assay) and expressed as adjusted (ANCOVA model) GMCs in ELISA units per milliliter (EU/mL). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. The ANCOVA model includes study group, smoking status (current or former), age category (50-59, 60-69, 70-80 years of age) and center as factors and the antibody concentration before Dose 1 as covariate. As per protocol set (PPS) sample size was not met in Sh_NTHi_Mcat_3 and Sh_NTHi-Mcat_6 groups then timeframe was adapted as follows: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181 in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group) | At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181, in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibody Concentrations in Terms of GMCs, Before First NTHi-Mcat Vaccine | GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations) | Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 for Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 for NTHi-Mcat group) | 
| Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibody Concentrations in Terms of GMCs, One-month Post Dose-2 of NTHi-Mcat Vaccine | GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations) before the first dose of NTHi-Mcat vaccine | At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group) | 
| Percentage of Seropositive Subjects for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibodies Before First NTHi-Mcat Vaccine | A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI is defined using the assay lower limit of quantification (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively | Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group) | 
| Percentage of Subjects Seropositive for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibodies, One-month Post Dose-2 of NTHi-Mcat Vaccine | A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI are defined using the assay (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively | At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group) | 
| Frequency of Specific Cluster of Differentiation 4 (CD4+) T-cells Against NTHi and Mcat Antigens for Evaluation of Cell-mediated Immune (CMI) Response, Before First Dose of NTHi-Mcat Vaccine | Frequency of specific CD4+ T-cells was measured by flow cytometry intracellular cytokine staining (ICS) expressing at least 2 different markers among CD40 Ligand (CD40L), interleukin (IL)-2, IL-13, IL-17, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), upon in vitro stimulation | Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group) | 
| Frequency of CD4+ T-cells Against NTHi and Mcat Antigens for Evaluation of CMI Response, at One-month Post Dose 2 of NTHi-Mcat Vaccine | Frequency of specific CD4+ T-cells was measured by flow cytometry ICS expressing at least 2 different markers among CD40L, IL-2, IL-13, IL-17, TNF-α and IFN-γ, upon in vitro stimulation | At one month after second dose of NTHi-Mcat vaccine (Day 181, Day 241 and Day 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group) | 
| Percentage of Subjects With Reported Solicited Local Adverse Event (AE) | The percentage of subjects with at least one local solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed local symptoms were pain, redness and swelling. Any local injection site redness/swelling is scored as follows: diameter >=20 milli-meters | During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine | 
| Percentage of Subjects With Reported Solicited General AE | The percentage of subjects with at least one general solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed solicited general symptoms were Fatigue, Gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), Headache, Myalgia, Chills and Fever (oral cavity or axillary route - temperature equal or higher than [>=] 37.5 degrees Celsius [°C]) | During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine | 
| Percentage of Subjects With Any Unsolicited AE | An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. The percentage of subjects with at least one unsolicited AE, regardless of intensity or relationship to vaccination, during the 30-day follow-up period after any NTHi-Mcat vaccine dose are reported for each group. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event | During the 30-day follow-up period (i.e. day of vaccination and 29 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine | 
| Percentage of Subjects With Any Serious Adverse Event (SAE) During Epoch 001 | The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 1 up to and including Day 331, were reported for each group An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician | From Day 1 up to and including Day 331 (Epoch 001) | 
| Percentage of Subjects With Any Potential Immune-mediated Diseases (pIMD's) During Epoch 001 | pIMD's 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 Day 1 up to and including Day 331 (Epoch 001) | 
| Percentage of Subjects With Any SAE During Epoch 002 | The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 332 up to and including Day 661, are reported for each group. An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, requires hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician. | From Day 332 up to and including Day 661 (Epoch 002) | 
| Percentage of Subjects With Any pIMD's During Epoch 002 | pIMD's 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 Day 332 up to and including Day 661 (Epoch 002) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Chronic obstructive pulmonary disease (COPD), Non-typeable Haemophilus influenza, Moraxella catarrhalis, Shingrix, Herpes Zoster, Adjuvanted vaccines, Safety