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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      The purpose of this Phase 2 study is to evaluate two vaccine schedules of the investigational
      NTHi-Mcat vaccine.

      As the prevalence of COPD increases with age and as age has an influence on both the
      immunogenicity and reactogenicity of a vaccine, subjects 40-80 years old will be enrolled. As
      cigarette smoking is the most commonly encountered risk factor for COPD, adults with a
      smoking history of at least 10 pack-years will be selected in order to immunologically match
      the COPD population as much as possible. Literature data indeed suggest that alterations of
      the immune system start early on in smokers, before the COPD disease is recognized [Barcelo
      et al 2008; Droemann et al, 2005; Takanashi et al, 1999].

      Several formulations of a vaccine containing the NTHi antigens (10 or 30 µg) either
      non-adjuvanted or combined with different adjuvants (aluminium [Al], adjuvant system [AS]01E
      and AS04C) were already evaluated in two previous Phase 1 clinical trials (NTHI-002 in
      healthy adults aged 18 - 40 years and NTHI-003 in current and former healthy smokers of 50-70
      years old). The investigational vaccines were well-tolerated, with an acceptable safety and
      reactogenicity profile. These studies allowed the dose selection of the NTHi antigens (10 µg)
      and the adjuvant system (AS01E) evaluated for the first time in moderate and severe COPD
      patients aged 40-80 years in the Phase 2 study NTHI-004.

      The safety, reactogenicity and immunogenicity of different formulations of the NTHi-Mcat
      investigational vaccine have been evaluated in the Phase 1 study in healthy adults aged 18-40
      years and in current and former smokers aged 50-70 years (study NTHI MCAT-001). Based on
      results obtained up to 30 days post-Dose 2 from this study, the AS01E-adjuvanted formulation
      containing 10 µg of NTHi proteins PD and PE-PilA and 3.3 µg of UspA2 has been selected for
      evaluation in the current NTHI MCAT-008 study. The current study will evaluate the impact of
      a 3rd dose (following a 0-2 month vaccination schedule), either given at 6 months or at 12
      months after the first dose. The primary aim is to assess the safety of the additional dose.
      The study will also investigate how the two schedules improve the persistence of antibody
      response.

      To this end, adults aged 40 to 80 years with a smoking history of at least 10 pack-years,
      will receive 2 doses of the NTHi-Mcat investigational vaccine at 0 and 2 months in both study
      arms. Following these 2 doses, one study arm will receive a 3rd dose of the investigational
      NTHi-Mcat vaccine at 6 months and a placebo control at 12 months (Schedule 1) and the other
      study arm will receive a placebo control at 6 months and a 3rd dose of the investigational
      NTHi-Mcat vaccine at 12 months (Schedule 2).
    

Intervention name(s): NTHi Mcat investigational vaccine (GSK3277511A); Placebo
Intervention type(s): Biological; Biological
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Non-typeable Haemophilus influenzae; Moraxella catarrhalis; Safety; Third vaccine dose; Vaccination; Immunogenicity