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A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GlaxoSmithkline (GSK) Biologicals' Investigational Vaccine GSK2838504A When Administered to Chronic Obstructive Pulmonary Disease (COPD) Patients With Persistent Airflow Obstruction.

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ClinicalTrials.gov Identifier: NCT02075541
Recruitment Status : Completed
First Posted : March 3, 2014
Results First Posted : August 1, 2018
Last Update Posted : August 1, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The purpose of this Phase II study is to assess the safety, reactogenicity and immunogenicity of the investigational Non-typeable Haemophilus influenzae (NTHi) vaccine in patients with moderate and severe persistent airflow obstruction.

Condition or disease Intervention/treatment Phase
Respiratory Disorders Biological: NTHi-10-AS01E Drug: NaCl Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 145 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: An Observer-blind Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Investigational Vaccine GSK2838504A When Administered to Chronic Obstructive Pulmonary Disease (COPD) Patients
Actual Study Start Date : July 8, 2014
Actual Primary Completion Date : April 19, 2017
Actual Study Completion Date : April 19, 2017

Arm Intervention/treatment
Experimental: 10-AS01E group
Subjects in this group will receive the investigational NTHi vaccine.
Biological: NTHi-10-AS01E
Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

Placebo Comparator: Control group
Subjects in this group will receive placebo.
Drug: NaCl Placebo
Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.




Primary Outcome Measures :
  1. Number of Subjects With Any Solicited Local Adverse Events (AEs). [ Time Frame: During a 7-day follow-up period (from Day 0 to Day 6) after first dose. ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.

  2. Number of Subjects With Any Solicited Local AEs. [ Time Frame: During a 7-day follow-up period (from Day 60 to Day 66) after second dose. ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.

  3. Number of Subjects With Any Solicited General AEs. [ Time Frame: During a 7-day follow-up period (from Day 0 to Day 6) following the first dose. ]
    Assessed solicited general symptoms are fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), headache, fever [defined as oral temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade.

  4. Number of Subjects With Any Solicited General AEs [ Time Frame: During a 7-day follow-up period (from Day 60 to Day 66) following the second dose. ]
    Assessed solicited general symptoms are fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), headache, fever (defined as oral temperature equal to or above 37.5 °C). Any = occurrence of the symptom regardless of intensity grade.

  5. Number of Subjects With Any Unsolicited AEs. [ Time Frame: During the 30-day follow-up period (from Day 0 to Day 29) following the first dose. ]
    Assessed unsolicited AEs covered 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.

  6. Number of Subjects With Any Unsolicited AEs [ Time Frame: During the 30-day follow-up period (from Day 60 to Day 89) following the second dose. ]
    Assessed unsolicited AEs covered 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.

  7. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 0. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  8. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 7. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  9. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 30. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  10. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 60. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  11. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 67. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  12. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 90. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  13. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 270. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  14. Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality. [ Time Frame: At Day 450. ]
    Assessed haematological parameters are complete blood cell count: Leukocytes [white blood cells (WBC)], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  15. Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs). [ Time Frame: From first vaccination (Day 0) up to study conclusion (Day 450). ]
    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.

  16. Number of Subjects With Any Serious Adverse Events (SAEs). [ Time Frame: From first vaccination (Day 0) up to study conclusion (Day 450). ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity or are a congenital anomaly/ birth defect in the offspring of a study subject.


Secondary Outcome Measures :
  1. Concentration of Anti Protein D (Anti-PD) Total Immunoglobulin G (IgG) Antibodies Against the NTHi Vaccine Antigens. [ Time Frame: At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450. ]
    Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs) in ELISA units per millilitre (EL.U/mL). The cut-off of the assay was 153 EL.U/mL for anti-PD.

  2. Concentration of Anti Protein E (Anti-PE) Total IgG Antibodies Against the NTHi Vaccine Antigens. [ Time Frame: At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450 ]
    Antibody concentrations were measured by ELISA and expressed as GMCs in EL.U/mL. The cut-off of the assay was 8 EL.U/mL for anti-PE.

  3. Concentration of Anti-PilA Total IgG Antibodies Against the NTHi Vaccine Antigens. [ Time Frame: At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450. ]
    Antibody concentrations were measured by ELISA and expressed as GMCs in EL.U/mL. The cut-off of the assay was 7 EL.U/mL for anti-PilA.

  4. Frequency of Specific Cluster of Differentiation 4 (CD4+) T-cells Against NTHi Antigens Collected for Evaluation of Cell-mediated Immune Response. [ Time Frame: At Day 0, Day 90, Day 270 and at Day 450. ]
    Frequency of specific CD4+ T-cells were measured by flow cytometry intracellular cytokine staining (ICS) expressing two or more markers [such as Interleukin-2 (IL-2), IL-13, IL-17, Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α) and Cluster of Differentiation 40 Ligand (CD40L)].The frequency of specific CD4+ T-cells are summarised [descriptive statistics: Mean and standard deviation (SD)] against each antigen (PD, PE and PilA), by group at each time point during which blood samples are collected for CMI.

  5. Frequency of Specific CD8+ T-cells Against NTHi Antigens Collected for Evaluation of Cell-mediated Immune Response. [ Time Frame: At Day 0, Day 90, Day 270 and at Day 450. ]
    Frequency of specific CD8+ T-cells were measured by flow cytometry ICS expressing two or more markers (such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L).The frequency of specific CD8+ T-cells are summarised [descriptive statistics: Mean and standard deviation (SD)] against each antigen (PD, PE and PilA), by group at each time point during which blood samples are collected for CMI.



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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
  • A male or female between, and including, 40 and 80 years of age at the time of the first vaccination.
  • Written informed consent obtained from the subject.
  • Confirmed diagnosis of COPD with forced expiratory volume in 1 second (FEV1) over forced vital capacity (FVC) ratio (FEV1/FVC) < 0.7, AND FEV1 < 80% and ≥ 30% predicted.
  • Current or former smoker with a cigarette smoking history of ≥ 10 pack-years.
  • Stable COPD patient with documented history of at least 1 moderate or severe acute exacerbation of COPD within the 12 months before Screening.
  • Regular sputum producer.
  • Capable to comply with the daily electronic Diary Card completion throughout the study period, according to investigator's judgement at Visit 1.
  • 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 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:

  • 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.
  • Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, 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, with the exception of any influenza or pneumococcal vaccine which may be administered ≥ 15 days preceding or following any study vaccine dose.
  • Previous vaccination with any vaccine containing NTHi antigens.
  • Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
  • Chronic administration of non-steroid immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • History of immune-mediated disease other than COPD.
  • Administration of systemic corticosteroids within the 30 days before Screening.
  • Administration of systemic antibiotics within the 30 days before Screening.
  • Chronic use of antibiotics for prevention of acute exacerbations of COPD (AECOPD).
  • Receiving oxygen therapy.
  • Planned lung transplantation.
  • Planned/ underwent lung resection surgery.
  • Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD.
  • Diagnosed with a respiratory disorder other than COPD, or chest X-ray/ CT scan revealing evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Subjects with allergic rhinitis can be enrolled.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines and/ or the bronchodilator used for spirometry assessment during the study.
  • Contraindication for spirometry testing.
  • Clinically significant abnormality in haematology or biochemistry parameter.
  • Acute cardiac insufficiency.
  • Malignancies within the previous 5 years or lymphoproliferative disorder.
  • Any known disease or condition likely to cause death during the study period.
  • Acute disease and/ or fever at the time of Screening.

    • Fever is defined as oral or axillary temperature ≥ 37.5°C. The preferred route for recording temperature in this study will be oral.
    • Subjects with acute disease and/ or fever at the time of Screening may be enrolled at a later date if enrolment is still open. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  • Pregnant or lactating female.
  • Current alcoholism and/or drug abuse.
  • Other condition which the investigator judges may put the safety of the subject at risk through study participation or which may interfere with the study findings.
  • Planned move to a location that will complicate participation in the trial through study end.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02075541


Locations
Sweden
GSK Investigational Site
Eskilstuna, Sweden, SE-631 88
GSK Investigational Site
Göteborg, Sweden, SE-413 45
GSK Investigational Site
Örebro, Sweden, SE-703 62
United Kingdom
GSK Investigational Site
Llanelli, Carmarthenshire, United Kingdom, SA14 8QF
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
GSK Investigational Site
Stoke on Trent, Staffordshire, United Kingdom, ST4 6QG
GSK Investigational Site
Bradford, United Kingdom, BD9 6RJ
GSK Investigational Site
Dundee, United Kingdom, DD1 9SY
GSK Investigational Site
Edinburgh, United Kingdom, EH16 4SA
GSK Investigational Site
Liverpool, United Kingdom, L9 7AL
GSK Investigational Site
Poole, Dorset, United Kingdom, BH15 2JB
GSK Investigational Site
Salford, United Kingdom, M6 8HD
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
GSK Investigational Site
Wolverhampton, United Kingdom, WV10 0QP
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] April 15, 2016
Statistical Analysis Plan  [PDF] February 9, 2016


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02075541     History of Changes
Other Study ID Numbers: 200157
2013-003062-13 ( EudraCT Number )
First Posted: March 3, 2014    Key Record Dates
Results First Posted: August 1, 2018
Last Update Posted: August 1, 2018
Last Verified: June 2018

Keywords provided by GlaxoSmithKline:
Immunogenicity
Observer-blind
Reactogenicity
Chronic Obstructive Pulmonary Disease
Safety

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiration Disorders
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs