A Study to Test if a Third Dose of the Vaccine is Safe in Current and Former Smokers Aged 40 to 80 Years Old and to Gather Information on the Immune Response Following the Third Dose of the Vaccine
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 and a third dose administered at either Day 181 or Day 361, according to each vaccination scheduling defined per protocol.; One dose administered intramuscularly at either Day 181 or Day 361 in the deltoid region of the non-dominant arm.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: 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) 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 (e.g. study nurse) 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).
The laboratory in charge of the laboratory testing will be blinded to the treatment, and codes will be used to link the subject and study (without any link to the treatment attributed to the subject) to each sample.
Enrollment: 200.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Non-typeable Haemophilus influenzae; Moraxella catarrhalis; Safety; Third vaccine dose; Vaccination; Immunogenicity

Summary:

      The purpose of this study is to test two different vaccine schedules to be used for
      administering the investigational NTHi Mcat vaccine that will be targeting patients with
      chronic obstructive pulmonary disease (COPD) to prevent acute exacerbations. An acute
      exacerbation is when the breathlessness in COPD patients will get even worse than it normally
      already is, sometimes to the point where oxygen therapy is required.

      In previous studies, study participants have received two doses of the vaccine according to a
      0, 2 month vaccination schedule, in addition to standard care. The current study will find
      out if a third dose of the study vaccine against NTHi/Mcat is safe and working well. The
      study will also investigate if the third dose of vaccine works best when given after 6 months
      or after 12 months.
    

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.

          -  Current or former smoker with a cigarette smoking history of ≥ 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:

          -  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
             vaccines (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.

          -  Chronic administration of immunosuppressants or other immune-modifying drugs during
             the period starting six months prior to the first vaccine dose. For corticosteroids,
             this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are
             allowed.

          -  Administration of long-acting immune-modifying drugs at any time 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 and ending 30 days after the last dose
             of vaccine administration, 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.

          -  Previous vaccination with any vaccine containing NTHi and/or Mcat antigens.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination.

          -  History of or current autoimmune disease.

          -  History of any reaction or hypersensitivity likely to be exacerbated by any component
             of the vaccine.

          -  Acute disease and/or fever at the time of enrolment.

               -  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.

          -  Administration of immunoglobulins and/or any blood products during the period starting
             3 months before the first dose of study vaccine or planned administration during the
             study period.

          -  Pregnant or lactating female.

          -  Current alcoholism and/or drug abuse.

          -  Female planning to become pregnant or planning to discontinue contraceptive
             precautions.

          -  Diagnosed with a respiratory disorder.

          -  Has significant disease, in the opinion of the investigator, likely to interfere with
             the study and/or likely to cause death within the study duration.

          -  Malignancies within previous 5 years or lymphoproliferative disorders.

          -  Any other condition that the investigator judges may interfere with study findings.