A Study to Test if the Vaccine is Working Well in Chronic Obstructive Pulmonary Disease (COPD) Patients Aged 40 to 80 Years Old to Reduce Episodes of Worsening Symptoms and to Gather Further Information on Safety and Immune Response.
Condition: Respiratory Disorders
MeSH terms: Respiration Disorders; Respiratory Tract Diseases
Intervention: NTHi Mcat investigational vaccine (GSK3277511A); Placebo
Intervention description: Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.; Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase IIB, randomised, observer-blind, placebo-controlled, multi-centric study with two parallel groups.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Data will be collected in an observer-blind manner. By observer-blind, it is meant that during the course of the study, the vaccine recipient and those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity and efficacy) will all be unaware of whether vaccine or placebo was administered. Each study site is responsible for having a blinding plan. To work in an observer-blind manner, vaccine preparation and administration will be done by authorised medical personnel who will not participate in any of the study clinical evaluation assays. Two teams of study personnel will hence be set up:
A team of unblinded personnel (responsible for the preparation and the administration of the vaccines)
A team of blinded personnel (responsible for the clinical evaluation of the subjects).
Enrollment: 606.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Immunogenicity; Vaccination; Chronic Obstructive Pulmonary Disease; Non-typeable Haemophilus influenzae; Acute exacerbation of COPD; Moraxella catarrhalis; Efficacy; Safety

Summary:

      The purpose of this study is to test if the vaccine is working well in COPD patients aged 40
      to 80 years old to reduce episodes of worsening symptoms ("exacerbations") and to gather
      further information on safety and immune response.

      In the current study, COPD patients with a history of acute exacerbations will receive 2
      doses of the investigational vaccine or placebo intramuscularly according to a 0, 2 month
      vaccination schedule, in addition to standard care.

      The effect of vaccination against two pathogens known to cause exacerbations (Non-typeable
      Haemophilus influenza [NTHi] and Moraxella catarrhalis [Mcat]) will be evaluated at
      pre-defined timepoints (scheduled study visits).

      In addition to the scheduled study visits, additional study visit(s) and/ or phone contact(s)
      will take place for each acute exacerbation of COPD occurring from first vaccination up to
      study conclusion.
    

Eligibility criteria:

        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 prior to performing any study
             specific procedure.

          -  A male or female between, and including, 40 and 80 years of age at the time of the
             first vaccination.

          -  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% predicted (GOLD 2,
             3 and 4).

          -  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 AECOPD
             within the 12 months before Screening.

               -  Patient for whom the last episode of AECOPD is resolved for at least 30 days at
                  the time of first vaccination.

                    -  A documented history of a COPD exacerbation is a medical record of worsening
                       COPD symptoms that required systemic/oral corticosteroids and/or antibiotics
                       (for a moderate exacerbation) or hospitalization (for a severe
                       exacerbation). Prior use of antibiotics alone does not qualify as an
                       exacerbation history unless the use was associated with treatment of
                       worsening symptoms of COPD, such as increased dyspnea, sputum volume, or
                       sputum purulence. Subject verbal reports are not acceptable.

          -  Capable of complying 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.
             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:

          -  Use of any investigational or non-registered product other than the study vaccine
             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.

          -  Any medical condition that in the judgment of the investigator would make
             intramuscular injection unsafe.

          -  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.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination.

          -  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.

          -  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.

          -  Chronic administration of immunosuppressants or other immune-modifying drugs during
             the period starting six months prior to the first vaccine dose (e.g. methotrexate).

          -  Administration of systemic corticosteroids within the 30 days before first
             vaccination.

        Subjects who received systemic corticosteroids within this period may be enrolled at a
        later date if enrolment is still open.

        Inhaled and topical steroids are allowed.

        • Administration of systemic antibiotics within the 30 days before first vaccination.

        Subjects who received systemic antibiotics within this period may be enrolled at a later
        date if enrolment is still open.

          -  Chronic use of antibiotics for prevention of AECOPD (e.g. azithromycin).

          -  Acute disease and/or fever at the time of first vaccination. Fever is defined as
             temperature ≥37.5°C. The preferred location for measuring temperature in this study
             will be the oral cavity or the axilla.

        Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection)
        without fever may be enrolled at the discretion of the investigator.

          -  Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen
             therapy >3L/min (Oxygen use ≤3L/min flow is not exclusionary).

          -  Planned lung transplantation.

          -  Lung resection: Subjects with planned lung volume reduction surgery during the study
             or within the 12 months prior to first vaccination.

          -  Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD.

          -  Diagnosed with a respiratory disorder other than COPD at time of enrolment (such as
             sarcoidosis, active tuberculosis, clinically significant bronchiectasis, clinically
             significant lung fibrosis, clinically significant pulmonary embolism, clinically
             significant pneumothorax, current diagnosis of asthma in the opinion of the
             investigator), 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 do not need to be excluded and may be enrolled at the discretion of the
             investigator.

          -  History of immune-mediated disease other than COPD. If the subject has any condition
             on the non-exhaustive list of potential immune-mediated diseases defined in the
             protocol, they must be excluded unless the aetiology is clearly documented to be
             non-immune mediated.

          -  Previous vaccination with any vaccine containing NTHi and/ or Mcat antigens.

          -  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.

          -  Unstable or life threatening cardiac disease: subjects with any of the following at
             Screening (Visit 1) would be excluded:

        Myocardial infarction or unstable angina in the last 6 months. Unstable or life threatening
        cardiac arrhythmia requiring intervention in the last 3 months NYHA Class IV Heart failure

          -  Malignancies within the previous 5 years or lymphoproliferative disorder.

          -  Any known disease or condition likely to cause death during the study period.

          -  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.