CClinicalTrials.gg
Sign In
CompletedNCT03281876Updated Jan 11, 2021Results posted

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.

A Phase 2 interventional study of NTHi Mcat investigational vaccine (GSK3277511A) and Placebo in Respiratory Disorders, sponsored by GlaxoSmithKline. Completed at 67 sites in 8 countries. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-01-11.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
606
Allocation
Randomized
Ages
40 Years to 80 Years
Sex
All
01

Study 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.

Read the detailed description

The purpose of this Phase IIB proof-of-concept (POC) study in moderate to very severe COPD patients (i.e. GOLD grade 2, 3 and 4) aged 40 to 80 years with a history of moderate or severe acute exacerbations of COPD (AECOPD) in the previous 12 months is to evaluate whether the NTHi-Mcat vaccine can reduce the frequency of AECOPD in this population and to assess the vaccine's safety, reactogenicity and immunogenicity.

Several formulations of a vaccine containing the NTHi antigens (low or high formulation) either non-adjuvanted or combined with different adjuvants (aluminium [Al], adjuvant system) were already evaluated in two previous Phase I 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 (low formulation) and the adjuvant system currently evaluated for the first time in moderate and severe COPD patients aged 45 - 81 years in the Phase II study NTHI-004.

The safety, reactogenicity and immunogenicity of different formulations of the NTHi-Mcat investigational vaccine have been evaluated in the Phase I study in healthy adults aged 19 - 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 adjuvanted formulation containing NTHi proteins PD and PE-PilA and of UspA2 has been selected for evaluation in the current NTHI MCAT-002 study. Placebo will be used as a control. The NTHi-Mcat investigational vaccine and placebo will be given on top of standard of care to subjects in the respective study groups.

In the current study, moderate, severe and very severe COPD patients (i.e. GOLD grade 2, 3 and 4) with a history of AECOPD will receive 2 doses of the NTHi-Mcat investigational vaccine or placebo intramuscularly (IM) according to a 0, 2 month vaccination schedule, in addition to standard care.

Scheduled study visits, during which the effect of immunisation against NTHi and Mcat will be evaluated, will take place at pre-defined timepoints.

In addition to the scheduled study visits, ad hoc AECOPD-driven study visit(s) and/ or phone contact(s) will take place for each AECOPD occurring from first vaccination up to study conclusion:

  • An AECOPD visit will be scheduled as soon as possible after the onset of the AECOPD symptoms (maximum 96 hours after the onset of the symptoms).
  • Follow-up visit(s) and/or phone call(s) will take place to determine the end of the AECOPD.

Rationale for the protocol amendment:

  • CD8+ T cell component was removed from the secondary endpoint, but kept in the exploratory/tertiary endpoint. Previous clinical studies have shown that the investigational NTHi and NTHi-Mcat vaccines do not induce CD8+ T cell responses. This was observed in all studies performed with the NTHi vaccine and seen in the interim analysis of NTHi Mcat-001 study.
  • An exclusion criterion was updated to clarify that only subjects with clinically significant respiratory diseases other than COPD (e.g. clinically significant lung fibrosis, clinically significant pulmonary embolism) need to be excluded from study participation.
  • The polymerase chain reaction (PCR) assay for sputum samples was not designed to discriminate amongst Haemophilus influenzae (Hi) serotypes. Results from AERIS epidemiological study [Wilkinson, 2017] showed that more than 99% of these bacteria would be Non-Typeable Haemophilus influenzae (NTHi). Therefore, the protocol was updated to clarify that the presence of Hi bacteria in sputum during exacerbation will be used to determine AECOPD associated to NTHi.
  • The list of potential immune mediated diseases was updated (effective June 30th 2017).
  • The 87% confidence interval (CI) was removed from all secondary analyses. This confidence interval will only be maintained for the primary analysis because the 95% CIs are underpowered for this study. All other sensitivity analyses on different cohorts will be described using 95% CIs. As the primary objective will have both 87% and 95%, the sensitivity analyses can be interpreted with 95% CIs.
  • A Full-Analysis Set (FAS) that corresponds to an intent-to-treat analysis was added. The FAS will include all randomized subjects who will receive at least 1 vaccine administration and, as per intention-to-treat principle, a subject in the FAS will be analysed "as randomized" (i.e. according to the vaccine a subject was planned to receive irrespectively of his/her real exposure).
  • Cut-off values for anti-PE, anti-PilA and anti-UspA2 antibody ELISAs were updated following the re-set up of the assays.
  • Additional minor updates were based on the scientific and operational experience gained from current COPD studies.
02

Conditions studied

  • Respiratory Disorders

Keywords

  • Immunogenicity
  • Vaccination
  • Chronic Obstructive Pulmonary Disease
  • Non-typeable Haemophilus influenzae
  • Acute exacerbation of COPD
  • Moraxella catarrhalis
  • Efficacy
  • Safety
03

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
606 participants (actual)

Study arms

  • Experimental
    GSK3277511A Group

    Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2) at Day 1 and Day 61.

    Biological: NTHi Mcat investigational vaccine (GSK3277511A)

  • Placebo comparator
    CONTROL Group

    Healthy males and females, 40 to 80 years of age, who received two doses of placebo vaccine at Day 1 and Day 61.

    Biological: Placebo

Interventions

  • BiologicalNTHi Mcat investigational vaccine (GSK3277511A)

    Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.

  • BiologicalPlacebo

    Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.

05

What researchers measure

Primary outcomes

  1. Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year

    Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  2. Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year

    Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

Secondary outcomes

  1. Number of Subjects Reported With Each Solicited Local Adverse Event (AE)

    Assessed solicited local symptoms were pain, redness and swelling

    Time frame: During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61

  2. Number of Subjects Reported With Each Solicited General AE

    Assessed solicited general symptoms were Chills, fatigue, fever \[defined as (oral cavity or axillary) temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\], headache and myalgia.

    Time frame: During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61

  3. Number of Subjects Reported With Any Unsolicited Adverse Event (AE)

    An unsolicited AE covers 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 any solicited symptoms.

    Time frame: During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61

  4. Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs)

    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.

    Time frame: From first vaccination (Day 1) up to Study end (at Day 451)

  5. Number of Subjects Reported With Any Serious Adverse Event (SAE)

    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity

    Time frame: From first vaccination (Day 1) up to Study end (at Day 451)

  6. Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

    The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The severity of AECOPD can be graded according to the intensity of medical intervention required. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.

    Time frame: During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)

  7. Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

    The rates of any AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The intention of the analysis of the Rate during 3, 6, 9 and 12 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 and 0-12 months.

    Time frame: During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months, 0-12 months (observation starting 1 month post-Dose 2)

  8. Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

    The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: It is calculated proportionally to the follow-up time per subject and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for each period considered. The severity of AECOPD can be graded according to the intensity of medical intervention required. Mild = can be controlled with an increase in dosage of regular medications. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.

    Time frame: During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)

  9. Number of Subjects With First Moderate or Severe AECOPD

    Number of subjects with first occurrence of moderate or severe episode of AECOPD was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  10. Number of Subjects With First AECOPD of Any Severity

    Number of subjects with first occurrence of any episode of AECOPD of any severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  11. Number of Subjects With First AECOPD Classified by Severity

    Number of subjects with first occurrence of any episode of AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  12. Number of Days With Moderate and Severe AECOPDs

    The length of each AECOPD was tabulated and presented via descriptive statistics (mean, Standard Deviation) and expressed in Days.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  13. Number of Days With AECOPDs of Any Severity

    The length of each AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  14. Number of Days With AECOPDs Classified by Severity

    The length of each AECOPDs by severity was tabulated and presented via descriptive statistics (mean, Standard Deviation).

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  15. Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD

    The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by Polymerase chain reaction (PCR) analysis in sputum samples.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  16. Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity

    The rates of AECOPD of any severity were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by polymerase chain reaction (PCR) analysis in sputum samples.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  17. Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity

    The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: it is calculated proportionally to the follow-up time per subject, and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for the period considered. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  18. Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD

    Number of subjects with first occurrence of moderate or severe NTHI-associated and/or Mcat-associated AECOPD was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  19. Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity

    Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD of any severity was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  20. Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity

    Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  21. Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD

    The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  22. Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity

    The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  23. Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity

    The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

    Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

  24. Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA)

    Anti-Protein D (PD) antibody concentrations as determined by ELISA, and expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EU/mL). For anti-PD antibodies, the cut-off of the assay is 153 ELISA Units per millilitre (EU/mL.)

    Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

  25. Anti-PE Antibody Concentrations as Measured by ELISA

    Anti-Protein E (PE) antibody concentrations as determined by ELISA and expressed as GMCs in EU/mL For Anti-PE antibodies, the cut-off of the assay is 16 EU/mL.

    Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

  26. Anti-PilA Antibody Concentrations as Measured by ELISA

    Anti-Type IV pilus assembly protein (PilA) antibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-PilA antibodies, the cut-off of the assay is 8 EU/mL.

    Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

  27. Anti-UspA2 Antibody Concentrations as Measured by ELISA

    Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) aantibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-UspA2 antibodies, the cut-off of the assay is 28 EU/mL.

    Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

  28. Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

    The ICS staining assay was used to assess cell-mediated immunogenicity (CMI) responses. After Peripheral blood mononuclear cell (PBMC) stimulation with the relevant antigen, the frequency of PD specific CD4+ T-cells expressing selected combination of cytokines such as interleukine-2, 13, 17 (IL-2, IL-13, IL-17), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L) are evaluated by flow cytometry and expressed as mean and standard deviation.

    Time frame: At Day 1, Day 91, Day 271 and at Day 451

  29. Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

    The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PE specific CD4+ T-cells expressing selected combination of cytokines such as (IL-2, IL-13, IL-17), IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

    Time frame: At Day 1, Day 91, Day 271 and at Day 451

  30. Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

    The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PilA specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

    Time frame: At Day 1, Day 91, Day 271 and at Day 451

  31. Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

    The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of UspA2 specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

    Time frame: At Day 1, Day 91, Day 271 and at Day 451

06

Results

Posted Jan 11, 2021

Participant flow

Participant flow — Overall Study
MilestoneGSK3277511A GroupControl Group
Started304302
Completed281263
Not completed2339
Withdrew: Adverse event415
Withdrew: Lost to follow-up14
Withdrew: Withdrawal by subject1115
Withdrew: Migrated / moved from the study area20
Withdrew: Other55

Outcome measures

PrimaryRate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year

Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Number · exacerbations per person-year
Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year
exacerbations per person-yearGSK3277511A GroupControl Group
Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year1.22 (1.09 to 1.36)1.17 (1.06 to 1.3)
Statistical analysis
  • GSK3277511A Group vs Control Group · Negative Binomial regression · p = 0.8157 · Other: vaccine efficacy rate: -2.26 · 87% CI -18.27 to 11.58Negative Binomial model with arm, country, gold grade, history of exacerbation and age category as covariates and log time as offset variable
PrimaryRate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year

Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Number · exacerbations per person-year
Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year
exacerbations per person-yearGSK3277511A GroupControl Group
Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year1.22 (1.05 to 1.41)1.17 (1.02 to 1.34)
Statistical analysis
  • GSK3277511A Group vs Control Group · Negative Binomial regression · p = 0.8157 · Other: vaccine efficacy rate: -2.26 · 95% CI -23.45 to 15.29Negative Binomial model with arm, country, gold grade, history of exacerbation and age category as covariates and log time as offset variable
SecondaryNumber of Subjects Reported With Each Solicited Local Adverse Event (AE)

Assessed solicited local symptoms were pain, redness and swelling

Time frame:
During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61
Reported as:
Count of participants · Participants
Number of Subjects Reported With Each Solicited Local Adverse Event (AE)
ParticipantsGSK3277511A GroupControl Group
Pain, Dose 115316
Pain, Dose 216313
Redness (mm), Dose 1181
Redness (mm), Dose 2370
Swelling (mm), Dose 1132
Swelling (mm), Dose 2310
SecondaryNumber of Subjects Reported With Each Solicited General AE

Assessed solicited general symptoms were Chills, fatigue, fever \[defined as (oral cavity or axillary) temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\], headache and myalgia.

Time frame:
During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61
Reported as:
Count of participants · Participants
Number of Subjects Reported With Each Solicited General AE
ParticipantsGSK3277511A GroupControl Group
Chills, Dose 12935
Chills, Dose 23528
Fatigue, Dose 1157167
Fatigue, Dose 2136130
Fever, Dose 12425
Fever, Dose 21811
Gastrointestinal symptoms, Dose 14754
Gastrointestinal symptoms, Dose 23935
Headache, Dose 19876
Headache, Dose 27564
Myalgia, Dose 17872
Myalgia, Dose 27443
SecondaryNumber of Subjects Reported With Any Unsolicited Adverse Event (AE)

An unsolicited AE covers 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 any solicited symptoms.

Time frame:
During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61
Reported as:
Count of participants · Participants
Number of Subjects Reported With Any Unsolicited Adverse Event (AE)
ParticipantsGSK3277511A GroupControl Group
Number of Subjects Reported With Any Unsolicited Adverse Event (AE)110103
SecondaryNumber of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs)

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.

Time frame:
From first vaccination (Day 1) up to Study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs)
ParticipantsGSK3277511A GroupControl Group
Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs)63
SecondaryNumber of Subjects Reported With Any Serious Adverse Event (SAE)

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity

Time frame:
From first vaccination (Day 1) up to Study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects Reported With Any Serious Adverse Event (SAE)
ParticipantsGSK3277511A GroupControl Group
Number of Subjects Reported With Any Serious Adverse Event (SAE)8999
SecondaryRate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The severity of AECOPD can be graded according to the intensity of medical intervention required. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.

Time frame:
During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)
Reported as:
Number · exacerbations per person-year
Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period
exacerbations per person-yearGSK3277511A GroupControl Group
FROM 0 TO 3 MONTHS1.35 (1.1 to 1.66)1.15 (0.92 to 1.43)
FROM 3 TO 6 MONTHS1.33 (1.08 to 1.63)1.44 (1.19 to 1.75)
FROM 6 TO 9 MONTHS1.36 (1.11 to 1.67)1.19 (0.96 to 1.48)
FROM 9 TO 12 MONTHS0.87 (0.69 to 1.11)0.9 (0.71 to 1.14)
SecondaryRate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

The rates of any AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The intention of the analysis of the Rate during 3, 6, 9 and 12 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 and 0-12 months.

Time frame:
During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months, 0-12 months (observation starting 1 month post-Dose 2)
Reported as:
Number · exacerbations per person-year
Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period
exacerbations per person-yearGSK3277511A GroupControl Group
FROM 0 TO 3 MONTHS1.47 (1.21 to 1.79)1.33 (1.09 to 1.63)
FROM 3 TO 6 MONTHS1.56 (1.29 to 1.89)1.56 (1.29 to 1.88)
FROM 6 TO 9 MONTHS1.49 (1.23 to 1.82)1.29 (1.05 to 1.59)
FROM 9 TO 12 MONTHS0.98 (0.78 to 1.22)1.04 (0.84 to 1.3)
From 0 TO 12 MONTHS1.36 (1.19 to 1.57)1.31 (1.15 to 1.48)
Statistical analysis
  • GSK3277511A Group vs Control Group · Negative Binomial regression · p = 0.7700 · Vaccine efficacy rate: -2.72 · 95% CI -22.95 to 14.19
SecondaryExacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: It is calculated proportionally to the follow-up time per subject and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for each period considered. The severity of AECOPD can be graded according to the intensity of medical intervention required. Mild = can be controlled with an increase in dosage of regular medications. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.

Time frame:
During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)
Reported as:
Mean · exacerbations per person
Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period
exacerbations per personGSK3277511A GroupControl Group
MILD, FROM 0 TO 3 MONTHS0.02 ± 0.150.03 ± 0.20
MILD, FROM 3 TO 6 MONTHS0.05 ± 0.240.02 ± 0.14
MILD, FROM 6 TO 9 MONTHS0.03 ± 0.190.03 ± 0.18
MILD, FROM 9 TO 12 MONTHS0.03 ± 0.170.03 ± 0.16
MODERATE, FROM 0 TO 3 MONTHS0.29 ± 0.620.23 ± 0.48
MODERATE, FROM 3 TO 6 MONTHS0.27 ± 0.510.3 ± 0.57
MODERATE, FROM 6 TO 9 MONTHS0.3 ± 0.560.25 ± 0.51
MODERATE, FROM 9 TO 12 MONTHS0.2 ± 0.440.17 ± 0.42
SEVERE, FROM 0 TO 3 MONTHS0.04 ± 0.240.05 ± 0.23
SEVERE, FROM 3 TO 6 MONTHS0.05 ± 0.220.06 ± 0.29
SEVERE, FROM 6 TO 9 MONTHS0.05 ± 0.290.05 ± 0.24
SEVERE, FROM 9 TO 12 MONTHS0.01 ± 0.110.05 ± 0.24
SecondaryNumber of Subjects With First Moderate or Severe AECOPD

Number of subjects with first occurrence of moderate or severe episode of AECOPD was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects With First Moderate or Severe AECOPD
ParticipantsGSK3277511A GroupControl Group
Number of Subjects With First Moderate or Severe AECOPD158176
Statistical analysis
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.5751 · Hazard ratio (hr): 0.94 · 95% CI 0.758 to 1.166Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
SecondaryNumber of Subjects With First AECOPD of Any Severity

Number of subjects with first occurrence of any episode of AECOPD of any severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects With First AECOPD of Any Severity
ParticipantsGSK3277511A GroupControl Group
Number of Subjects With First AECOPD of Any Severity168188
Statistical analysis
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.5194 · Hazard ratio (hr): 0.934 · 95% CI 0.758 to 1.15Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
SecondaryNumber of Subjects With First AECOPD Classified by Severity

Number of subjects with first occurrence of any episode of AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects With First AECOPD Classified by Severity
ParticipantsGSK3277511A GroupControl Group
AFTER 1 MONTH POST DOSE 2, MILD2727
AFTER 1 MONTH POST DOSE 2, MODERATE144154
AFTER 1 MONTH POST DOSE 2, SEVERE3041
Statistical analysis
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.8581 · Hazard ratio (hr): 1.05 · 95% CI 0.616 to 1.791Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.9634 · Hazard ratio (hr): 0.995 · 95% CI 0.792 to 1.249Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.1755 · Hazard ratio (hr): 0.722 · 95% CI 0.45 to 1.157Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
SecondaryNumber of Days With Moderate and Severe AECOPDs

The length of each AECOPD was tabulated and presented via descriptive statistics (mean, Standard Deviation) and expressed in Days.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · Days
Number of Days With Moderate and Severe AECOPDs
DaysGSK3277511A GroupControl Group
Number of Days With Moderate and Severe AECOPDs16.6 ± 14.2915.6 ± 13.93
SecondaryNumber of Days With AECOPDs of Any Severity

The length of each AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · Days
Number of Days With AECOPDs of Any Severity
DaysGSK3277511A GroupControl Group
Number of Days With AECOPDs of Any Severity15.9 ± 13.7915.3 ± 13.51
SecondaryNumber of Days With AECOPDs Classified by Severity

The length of each AECOPDs by severity was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · Days
Number of Days With AECOPDs Classified by Severity
DaysGSK3277511A GroupControl Group
MILD, AFTER 1 MONTH POST DOSE 28.9 ± 3.5612.3 ± 9.11
MODERATE, AFTER 1 MONTH POST DOSE 216.1 ± 13.9014.5 ± 10.50
SEVERE, AFTER 1 MONTH POST DOSE 220.4 ± 16.7821.2 ± 23.85
SecondaryRate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD

The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by Polymerase chain reaction (PCR) analysis in sputum samples.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Number · exacerbations per person-year
Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD
exacerbations per person-yearGSK3277511A GroupControl Group
Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD0.32 (0.25 to 0.42)0.32 (0.24 to 0.42)
SecondaryRate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity

The rates of AECOPD of any severity were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by polymerase chain reaction (PCR) analysis in sputum samples.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Number · exacerbations per person- year
Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity
exacerbations per person- yearGSK3277511A GroupControl Group
Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity0.39 (0.30 to 0.50)0.35 (0.27 to 0.45)
SecondaryExacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity

The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: it is calculated proportionally to the follow-up time per subject, and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for the period considered. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · exacerbations per person
Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity
exacerbations per personGSK3277511A GroupControl Group
MILD, AFTER 1 MONTH POST DOSE 20.06 ± 0.280.03 ± 0.21
MODERATE, AFTER 1 MONTH POST DOSE 20.3 ± 0.670.31 ± 0.74
SEVERE, AFTER 1 MONTH POST DOSE 20.02 ± 0.180.01 ± 0.11
SecondaryNumber of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD

Number of subjects with first occurrence of moderate or severe NTHI-associated and/or Mcat-associated AECOPD was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD
ParticipantsGSK3277511A GroupControl Group
Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD6262
Statistical analysis
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.9463 · Hazard ratio (hr): 1.038 · 95% CI 0.73 to 1.477Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
SecondaryNumber of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity

Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD of any severity was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity
ParticipantsGSK3277511A GroupControl Group
Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity7067
Statistical analysis
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.6042 · Hazard ratio (hr): 1.093 · 95% CI 0.782 to 1.528Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
SecondaryNumber of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity

Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Count of participants · Participants
Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity
ParticipantsGSK3277511A GroupControl Group
AFTER 1 MONTH POST DOSE 2, MILD157
AFTER 1 MONTH POST DOSE 2, MODERATE5859
AFTER 1 MONTH POST DOSE 2, SEVERE44
Statistical analysis
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.0777 · Hazard ratio (hr): 2.243 · 95% CI 0.914 to 5.504Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.9121 · Hazard ratio (hr): 1.021 · 95% CI 0.71 to 1.467Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
  • GSK3277511A Group vs Control Group · Regression, Cox · p = 0.8737 · Hazard ratio (hr): 1.12 · 95% CI 0.278 to 4.502Analysis using Cox proportional hazard regression including history of exacerbation, study treatment, GOLD grade and age group as covariate.
SecondaryNumber of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD

The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · Days
Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD
DaysGSK3277511A GroupControl Group
Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD14 ± 10.4312.3 ± 5.59
SecondaryNumber of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity

The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · Days
Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity
DaysGSK3277511A GroupControl Group
Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity13.3 ± 9.7612.1 ± 5.72
SecondaryNumber of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity

The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Time frame:
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Reported as:
Mean · Days
Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity
DaysGSK3277511A GroupControl Group
AFTER 1 MONTH POST DOSE 2, MILD9.5 ± 3.549.9 ± 6.83
AFTER 1 MONTH POST DOSE 2, MODERATE13.8 ± 10.4112.5 ± 5.62
AFTER 1 MONTH POST DOSE 2, SEVERE17.3 ± 11.027.5 ± 1.00
SecondaryAnti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA)

Anti-Protein D (PD) antibody concentrations as determined by ELISA, and expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EU/mL). For anti-PD antibodies, the cut-off of the assay is 153 ELISA Units per millilitre (EU/mL.)

Time frame:
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Reported as:
Geometric mean · EU/mL.
Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA)
EU/mL.GSK3277511A GroupControl Group
Day 1103.7 (93.8 to 114.7)95.4 (86.3 to 105.4)
Day 311048.1 (910.2 to 1206.8)98.2 (85.3 to 113.1)
Day 61654.6 (572.3 to 748.9)95.5 (83.6 to 109.1)
Day 911521.4 (1357.6 to 1704.9)90.3 (80.6 to 101.3)
Day 271546 (480.3 to 620.8)94.8 (83.6 to 107.4)
Day 451444.1 (390.2 to 505.4)97.9 (85.9 to 111.5)
SecondaryAnti-PE Antibody Concentrations as Measured by ELISA

Anti-Protein E (PE) antibody concentrations as determined by ELISA and expressed as GMCs in EU/mL For Anti-PE antibodies, the cut-off of the assay is 16 EU/mL.

Time frame:
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Reported as:
Geometric mean · EU/mL.
Anti-PE Antibody Concentrations as Measured by ELISA
EU/mL.GSK3277511A GroupControl Group
Day 120.9 (17.6 to 24.8)21.6 (18.2 to 25.7)
Day 311108.1 (921.5 to 1332.5)20.7 (17.2 to 24.9)
Day 61872.8 (726.6 to 1048.3)20.5 (17.1 to 24.6)
Day 916020 (5181.2 to 6994.7)20.1 (17.3 to 23.4)
Day 2711254.9 (1069.5 to 1472.5)19.3 (16.5 to 22.5)
Day 451835.2 (715.0 to 975.6)19.7 (16.8 to 23.0)
SecondaryAnti-PilA Antibody Concentrations as Measured by ELISA

Anti-Type IV pilus assembly protein (PilA) antibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-PilA antibodies, the cut-off of the assay is 8 EU/mL.

Time frame:
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Reported as:
Geometric mean · EU/mL.
Anti-PilA Antibody Concentrations as Measured by ELISA
EU/mL.GSK3277511A GroupControl Group
Day 18.3 (6.9 to 9.8)8.5 (7.1 to 10.1)
Day 31153 (124.2 to 188.6)9.2 (7.5 to 11.4)
Day 61134.2 (109.7 to 164.2)8.8 (7.2 to 10.8)
Day 91913.5 (770.5 to 1082.9)8.9 (7.5 to 10.5)
Day 271189.6 (159.2 to 225.7)8 (6.8 to 9.5)
Day 451126.5 (106.1 to 150.8)8.3 (6.9 to 9.9)
SecondaryAnti-UspA2 Antibody Concentrations as Measured by ELISA

Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) aantibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-UspA2 antibodies, the cut-off of the assay is 28 EU/mL.

Time frame:
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Reported as:
Geometric mean · EU/mL
Anti-UspA2 Antibody Concentrations as Measured by ELISA
EU/mLGSK3277511A GroupControl Group
Day 1540.3 (452.6 to 645.0)604.7 (507.2 to 721.0)
Day 311092.1 (997.5 to 1195.5)485.2 (442.9 to 531.6)
Day 61848.7 (781.5 to 921.5)473.5 (436.2 to 513.9)
Day 911223.7 (1110.8 to 1348.0)446 (404.5 to 491.8)
Day 271645.1 (582.1 to 714.8)445.4 (402.7 to 492.6)
Day 451575.9 (512.9 to 646.7)468.5 (416.5 to 527.1)
SecondaryFrequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess cell-mediated immunogenicity (CMI) responses. After Peripheral blood mononuclear cell (PBMC) stimulation with the relevant antigen, the frequency of PD specific CD4+ T-cells expressing selected combination of cytokines such as interleukine-2, 13, 17 (IL-2, IL-13, IL-17), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L) are evaluated by flow cytometry and expressed as mean and standard deviation.

Time frame:
At Day 1, Day 91, Day 271 and at Day 451
Reported as:
Mean · T cells/million cells
Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
T cells/million cellsGSK3277511A GroupControl Group
Day 156.6 ± 125.759.7 ± 118.2
Day 91890.2 ± 988.855.8 ± 88.2
Day 271364.6 ± 363.951.8 ± 90.9
Day 451267 ± 282.646.7 ± 101.1
SecondaryFrequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PE specific CD4+ T-cells expressing selected combination of cytokines such as (IL-2, IL-13, IL-17), IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

Time frame:
At Day 1, Day 91, Day 271 and at Day 451
Reported as:
Mean · T cells/million cells
Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
T cells/million cellsGSK3277511A GroupControl Group
Day 163.1 ± 211.492.9 ± 266.0
Day 91797 ± 1082.976.2 ± 195.0
Day 271384.8 ± 539.961.4 ± 207.2
Day 451335.7 ± 493.781.2 ± 258.9
SecondaryFrequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PilA specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

Time frame:
At Day 1, Day 91, Day 271 and at Day 451
Reported as:
Mean · T cells/million cells
Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
T cells/million cellsGSK3277511A GroupControl Group
Day 126.2 ± 45.453.3 ± 95.9
Day 91305.8 ± 321.744.6 ± 114.8
Day 271137.3 ± 163.242.1 ± 78.2
Day 451141 ± 147.142.4 ± 95.3
SecondaryFrequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of UspA2 specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

Time frame:
At Day 1, Day 91, Day 271 and at Day 451
Reported as:
Mean · T cells/million cells
Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
T cells/million cellsGSK3277511A GroupControl Group
Day 166.1 ± 177.147.2 ± 85.8
Day 91646.3 ± 545.270.3 ± 94.6
Day 271330.5 ± 278.560.8 ± 80.0
Day 451331.3 ± 310.461.5 ± 89.2

Adverse events

Collected over Solicited AEs reported during the 7-day follow-up period and Unsolicited AEs reported during the 30-day follow-up period after any vaccination. SAEs reported from first vaccination (Day 1) up to Study end (at Day 451 - an average of 15 months).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GSK3277511A Group1/304 (0.3%)89/304 (29.3%)276/304 (90.8%)
Control Group10/302 (3.3%)99/302 (32.8%)247/302 (81.8%)
Most frequent serious events
Showing 10 of 146
Most frequent serious events
EventGSK3277511A GroupControl Group
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders41/30453/302
PneumoniaInfections and infestations5/30415/302
Acute respiratory failureRespiratory, thoracic and mediastinal disorders7/3047/302
Infective exacerbation of chronic obstructive airways diseaseInfections and infestations1/3044/302
Respiratory failureRespiratory, thoracic and mediastinal disorders2/3044/302
Atrial fibrillationCardiac disorders4/3042/302
InfluenzaInfections and infestations4/3042/302
Urinary tract infectionInfections and infestations0/3043/302
Transient ischaemic attackNervous system disorders3/3040/302
Cardiac failureCardiac disorders0/3042/302
Most frequent other events
Showing 10 of 159
Most frequent other events
EventGSK3277511A GroupControl Group
Injection site painGeneral disorders213/30430/302
FatigueGeneral disorders195/304197/302
HeadacheNervous system disorders127/304111/302
MyalgiaMusculoskeletal and connective tissue disorders115/30494/302
Gastrointestinal disorderGastrointestinal disorders71/30477/302
ChillsGeneral disorders52/30452/302
Injection site erythemaGeneral disorders43/3041/302
PyrexiaGeneral disorders39/30432/302
Injection site swellingGeneral disorders35/3043/302
NasopharyngitisInfections and infestations13/30413/302

Baseline characteristics

Age, Continuous
Age, Continuous(Years)GSK3277511A GroupControl GroupTotal
Mean65.7 ± 7.566.3 ± 7.366.0 ± 7.4
Sex: Female, Male
Sex: Female, Male(Participants)GSK3277511A GroupControl GroupTotal
Female120125245
Male184177361
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)GSK3277511A GroupControl GroupTotal
American Indian Or Alaska Native011
Asian - Central / South Asian Heritage202
Asian - South East Asian Heritage011
Black Or African American549
Other101
White - Arabic / North African Heritage202
White - Caucasian / European Heritage294296590
07

Study locations

67 sites
  • GSK Investigational Site
    Mesa, Arizona 85213, United States
  • GSK Investigational Site
    Phoenix, Arizona 85018, United States
  • GSK Investigational Site
    Phoenix, Arizona 85020, United States
  • GSK Investigational Site
    Palm Springs, California 92262, United States
  • GSK Investigational Site
    Clearwater, Florida 33765, United States
  • GSK Investigational Site
    Jacksonville, Florida 32205, United States
  • GSK Investigational Site
    Jacksonville, Florida 32216, United States
  • GSK Investigational Site
    Council Bluffs, Iowa 51503, United States
  • GSK Investigational Site
    Wichita, Kansas 67207, United States
  • GSK Investigational Site
    Missoula, Montana 59808, United States
  • GSK Investigational Site
    Neptune, New Jersey 07753, United States
  • GSK Investigational Site
    Charlotte, North Carolina 28207, United States
  • GSK Investigational Site
    Mooresville, North Carolina 28117, United States
  • GSK Investigational Site
    Winston-Salem, North Carolina 27103, United States
  • GSK Investigational Site
    Columbus, Ohio 43213, United States
  • GSK Investigational Site
    Corvallis, Oregon 97330, United States
  • GSK Investigational Site
    Medford, Oregon 97504, United States
  • GSK Investigational Site
    Erie, Pennsylvania 16508, United States
  • GSK Investigational Site
    Gaffney, South Carolina 29340, United States
  • GSK Investigational Site
    Mount Pleasant, South Carolina 29464, United States
  • GSK Investigational Site
    Spartanburg, South Carolina 29303, United States
  • GSK Investigational Site
    Union, South Carolina 29379, United States
  • GSK Investigational Site
    Abingdon, Virginia 24210, United States
  • GSK Investigational Site
    Richmond, Virginia 23225, United States
  • GSK Investigational Site
    Wenatchee, Washington 98801, United States
  • GSK Investigational Site
    Brussels, 1000, Belgium
  • GSK Investigational Site
    Genk, 3600, Belgium
  • GSK Investigational Site
    Gent, 9000, Belgium
  • GSK Investigational Site
    Kortrijk, 8500, Belgium
  • GSK Investigational Site
    Leuven, 3000, Belgium
  • GSK Investigational Site
    Liège, 4000, Belgium
  • GSK Investigational Site
    Edmonton, Alberta T6G 2G3, Canada
  • GSK Investigational Site
    Vancouver, British Columbia V5Z 1M9, Canada
  • GSK Investigational Site
    Halifax, Nova Scotia B3K 6R8, Canada
  • GSK Investigational Site
    Truro, Nova Scotia B2N 1L2, Canada
  • GSK Investigational Site
    Montreal, Quebec H3T1E2, Canada
  • GSK Investigational Site
    St-Charles-Borromée, Quebec J6E 2B4, Canada
  • GSK Investigational Site
    Quebec, G1V 4G5, Canada
  • GSK Investigational Site
    Brest Cedex, 29609, France
  • GSK Investigational Site
    Créteil cedex, 94010, France
  • GSK Investigational Site
    Marseille cedex 08, 13285, France
  • GSK Investigational Site
    Montpellier cedex 5, 34295, France
  • GSK Investigational Site
    Frankfurt, Hessen 60389, Germany
  • GSK Investigational Site
    Frankfurt, Hessen 60596, Germany
  • GSK Investigational Site
    Immenhausen, Hessen 34376, Germany
  • GSK Investigational Site
    Grosshansdorf, Schleswig-Holstein 22927, Germany
  • GSK Investigational Site
    Luebeck, Schleswig-Holstein 23552, Germany
  • GSK Investigational Site
    Magdeburg, 39120, Germany
  • GSK Investigational Site
    Cona (FE), Emilia-Romagna 44124, Italy
  • GSK Investigational Site
    Parma, Emilia-Romagna 43100, Italy
  • GSK Investigational Site
    Milano, Lombardia 20122, Italy
  • GSK Investigational Site
    Milano, Lombardia 20142, Italy
  • GSK Investigational Site
    Monza, Lombardia 20900, Italy
  • GSK Investigational Site
    Negrar, Veneto 37024, Italy
  • GSK Investigational Site
    Barcelona, 08003, Spain
  • GSK Investigational Site
    Centelles (Barcelona), 08540, Spain
  • GSK Investigational Site
    Elda, 03600, Spain
  • GSK Investigational Site
    La Roca Del Valles (Barcelona), 08430, Spain
  • GSK Investigational Site
    Madrid, 28007, Spain
  • GSK Investigational Site
    Pozuelo De Alarcón/Madrid, 28223, Spain
  • GSK Investigational Site
    Vic, 28500, Spain
  • GSK Investigational Site
    Portsmouth, Hampshire PO6 3LY, United Kingdom
  • GSK Investigational Site
    Bradford, BD9 6RJ, United Kingdom
  • GSK Investigational Site
    Dundee, DD1 9SY, United Kingdom
  • GSK Investigational Site
    Edinburgh, EH16 4SA, United Kingdom
  • GSK Investigational Site
    High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom
  • GSK Investigational Site
    Southampton, SO16 6YD, United Kingdom
08

References and documents

Publications

  • Arora AK, Chinsky K, Keller C, Mayers I, Pascual-Guardia S, Vera MP, Lambert C, Lombardi S, Rondini S, Tian S, Ulloa-Montoya F, Moraschini L, Casula D; NTHi-Mcat-002 study group. A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial. Vaccine. 2022 Sep 29;40(41):5924-5932. doi: 10.1016/j.vaccine.2022.08.053. Epub 2022 Sep 6. PubMed 36068109 ↗
  • Andreas S, Testa M, Boyer L, Brusselle G, Janssens W, Kerwin E, Papi A, Pek B, Puente-Maestu L, Saralaya D, Watz H, Wilkinson TMA, Casula D, Di Maro G, Lattanzi M, Moraschini L, Schoonbroodt S, Tasciotti A, Arora AK, Maltais F; NTHi-Mcat-002 study group. Non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine for the prevention of exacerbations in chronic obstructive pulmonary disease: a multicentre, randomised, placebo-controlled, observer-blinded, proof-of-concept, phase 2b trial. Lancet Respir Med. 2022 May;10(5):435-446. doi: 10.1016/S2213-2600(21)00502-6. Epub 2022 Jan 10. Erratum In: Lancet Respir Med. 2022 Aug;10(8):e77. doi: 10.1016/S2213-2600(22)00254-5. PubMed 35026180 ↗

Study documents

  • Study protocol · Mar 27, 2019
  • Statistical analysis plan · Nov 29, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03281876
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Sep 13, 2017
Start date
Nov 27, 2017
Primary completion
Mar 26, 2020
Completion
Mar 26, 2020
Results posted
Jan 11, 2021
Last update
Jan 11, 2021

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Respiration Disorders→

Other studies from this sponsor

GlaxoSmithKline

Start the discussion