Last reviewed · How we verify

NCT03281876

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.

Completed Phase 2 Results posted Last updated 11 January 2021
What this trial tests

Phase 2 trial testing NTHi Mcat investigational vaccine (GSK3277511A) in Respiratory Disorders in 606 participants. Completed in 26 March 2020.

Timeline
27 November 2017
Primary endpoint
26 March 2020
26 March 2020

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment606
Start date27 November 2017
Primary completion26 March 2020
Estimated completion26 March 2020
Sites67 locations across France, Italy, Belgium, United Kingdom, Germany, Canada, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 40 to 80, any sex, with Respiratory Disorders. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year Primary · From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

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

GroupValue95% CI
GSK3277511A Group1.221.09 – 1.36
Control Group1.171.06 – 1.3
Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year Primary · From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

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

GroupValue95% CI
GSK3277511A Group1.221.05 – 1.41
Control Group1.171.02 – 1.34
Number of Subjects Reported With Each Solicited Local Adverse Event (AE) Secondary · During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61

Assessed solicited local symptoms were pain, redness and swelling

Pain, Dose 1
GroupValue95% CI
GSK3277511A Group153
Control Group16
Pain, Dose 2
GroupValue95% CI
GSK3277511A Group163
Control Group13
Redness (mm), Dose 1
GroupValue95% CI
GSK3277511A Group18
Control Group1
Redness (mm), Dose 2
GroupValue95% CI
GSK3277511A Group37
Control Group0
Swelling (mm), Dose 1
GroupValue95% CI
GSK3277511A Group13
Control Group2
Swelling (mm), Dose 2
GroupValue95% CI
GSK3277511A Group31
Control Group0
Number of Subjects Reported With Each Solicited General AE Secondary · During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61

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.

Chills, Dose 1
GroupValue95% CI
GSK3277511A Group29
Control Group35
Chills, Dose 2
GroupValue95% CI
GSK3277511A Group35
Control Group28
Fatigue, Dose 1
GroupValue95% CI
GSK3277511A Group157
Control Group167
Fatigue, Dose 2
GroupValue95% CI
GSK3277511A Group136
Control Group130
Fever, Dose 1
GroupValue95% CI
GSK3277511A Group24
Control Group25
Fever, Dose 2
GroupValue95% CI
GSK3277511A Group18
Control Group11
Gastrointestinal symptoms, Dose 1
GroupValue95% CI
GSK3277511A Group47
Control Group54
Gastrointestinal symptoms, Dose 2
GroupValue95% CI
GSK3277511A Group39
Control Group35
Number of Subjects Reported With Any Unsolicited Adverse Event (AE) Secondary · During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61

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.

GroupValue95% CI
GSK3277511A Group110
Control Group103
Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs) Secondary · From first vaccination (Day 1) up to Study end (at Day 451)

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.

GroupValue95% CI
GSK3277511A Group6
Control Group3
Number of Subjects Reported With Any Serious Adverse Event (SAE) Secondary · From first vaccination (Day 1) up to Study end (at Day 451)

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

GroupValue95% CI
GSK3277511A Group89
Control Group99
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 Secondary · 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)

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

FROM 0 TO 3 MONTHS
GroupValue95% CI
GSK3277511A Group1.351.1 – 1.66
Control Group1.150.92 – 1.43
FROM 3 TO 6 MONTHS
GroupValue95% CI
GSK3277511A Group1.331.08 – 1.63
Control Group1.441.19 – 1.75
FROM 6 TO 9 MONTHS
GroupValue95% CI
GSK3277511A Group1.361.11 – 1.67
Control Group1.190.96 – 1.48
FROM 9 TO 12 MONTHS
GroupValue95% CI
GSK3277511A Group0.870.69 – 1.11
Control Group0.90.71 – 1.14
Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period Secondary · 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)

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.

FROM 0 TO 3 MONTHS
GroupValue95% CI
GSK3277511A Group1.471.21 – 1.79
Control Group1.331.09 – 1.63
FROM 3 TO 6 MONTHS
GroupValue95% CI
GSK3277511A Group1.561.29 – 1.89
Control Group1.561.29 – 1.88
FROM 6 TO 9 MONTHS
GroupValue95% CI
GSK3277511A Group1.491.23 – 1.82
Control Group1.291.05 – 1.59
FROM 9 TO 12 MONTHS
GroupValue95% CI
GSK3277511A Group0.980.78 – 1.22
Control Group1.040.84 – 1.3
From 0 TO 12 MONTHS
GroupValue95% CI
GSK3277511A Group1.361.19 – 1.57
Control Group1.311.15 – 1.48
Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period Secondary · 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)

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 hospitalizat

MILD, FROM 0 TO 3 MONTHS
GroupValue95% CI
GSK3277511A Group0.02± 0.15
Control Group0.03± 0.20
MILD, FROM 3 TO 6 MONTHS
GroupValue95% CI
GSK3277511A Group0.05± 0.24
Control Group0.02± 0.14
MILD, FROM 6 TO 9 MONTHS
GroupValue95% CI
GSK3277511A Group0.03± 0.19
Control Group0.03± 0.18
MILD, FROM 9 TO 12 MONTHS
GroupValue95% CI
GSK3277511A Group0.03± 0.17
Control Group0.03± 0.16
MODERATE, FROM 0 TO 3 MONTHS
GroupValue95% CI
GSK3277511A Group0.29± 0.62
Control Group0.23± 0.48
MODERATE, FROM 3 TO 6 MONTHS
GroupValue95% CI
GSK3277511A Group0.27± 0.51
Control Group0.3± 0.57
MODERATE, FROM 6 TO 9 MONTHS
GroupValue95% CI
GSK3277511A Group0.3± 0.56
Control Group0.25± 0.51
MODERATE, FROM 9 TO 12 MONTHS
GroupValue95% CI
GSK3277511A Group0.2± 0.44
Control Group0.17± 0.42
Number of Subjects With First Moderate or Severe AECOPD Secondary · From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

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.

GroupValue95% CI
GSK3277511A Group158
Control Group176
Number of Subjects With First AECOPD of Any Severity Secondary · From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

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.

GroupValue95% CI
GSK3277511A Group168
Control Group188

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK3277511A Group
Serious: 89/304 (29%)
Deaths: 1/304
Control Group
Serious: 99/302 (33%)
Deaths: 10/302

Serious adverse events (146 terms)

ReactionSystemGSK3277511A GroupControl Group
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
Infective exacerbation of chronic obstructive airways diseaseInfections and infestations
InfluenzaInfections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
Urinary tract infectionInfections and infestations
Transient ischaemic attackNervous system disorders
Acute myocardial infarctionCardiac disorders
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
BronchitisInfections and infestations
Pneumonia pneumococcalInfections and infestations
UrosepsisInfections and infestations
Adenocarcinoma of colonNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Alcohol withdrawal syndromePsychiatric disorders
Bronchitis chronicRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Acute left ventricular failureCardiac disorders
Angina pectorisCardiac disorders
Angina unstableCardiac disorders
ArrhythmiaCardiac disorders
Other adverse events (159 terms — click to expand)

ReactionSystemGSK3277511A GroupControl Group
Injection site painGeneral disorders
FatigueGeneral disorders
HeadacheNervous system disorders
MyalgiaMusculoskeletal and connective tissue disorders
Gastrointestinal disorderGastrointestinal disorders
ChillsGeneral disorders
Injection site erythemaGeneral disorders
PyrexiaGeneral disorders
Injection site swellingGeneral disorders
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
Oedema peripheralGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
SinusitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
CystitisInfections and infestations
GastroenteritisInfections and infestations
InfluenzaInfections and infestations
PneumoniaInfections and infestations
Nasal congestionRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
VertigoEar and labyrinth disorders
Dental cariesGastrointestinal disorders
ToothacheGastrointestinal disorders
Chest discomfortGeneral disorders
Gastroenteritis viralInfections and infestations
Oral candidiasisInfections and infestations
ContusionInjury, poisoning and procedural complications
Muscle spasmsMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
TenosynovitisMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
SyncopeNervous system disorders
AnxietyPsychiatric disorders
DepressionPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Chronic obstructive pulmonary disease, Pneumonia, Acute respiratory failure, Atrial fibrillation, Infective exacerbation of chronic obstructive airways disease, Influenza, Respiratory failure, Urinary tract infection.

Data from ClinicalTrials.gov NCT03281876 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Technologies to address antimicrobial resistance.
    Baker SJ, Payne DJ, Rappuoli R, De Gregorio E. · · 2018 · cited 143× · PMID 30559181 · DOI 10.1073/pnas.1717160115
  2. The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable <i>Haemophilus influenzae</i>.
    Su YC, Jalalvand F, Thegerström J, Riesbeck K. · · 2018 · cited 72× · PMID 30455693 · DOI 10.3389/fimmu.2018.02530
  3. 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.
    Andreas S, Testa M, Boyer L, Brusselle G, et al · · 2022 · cited 23× · PMID 35026180 · DOI 10.1016/s2213-2600(21)00502-6
  4. Real-time PCR has advantages over culture-based methods in identifying major airway bacterial pathogens in chronic obstructive pulmonary disease: Results from three clinical studies in Europe and North America.
    Schoonbroodt S, Ichanté JL, Boffé S, Devos N, et al · · 2022 · cited 13× · PMID 36909845 · DOI 10.3389/fmicb.2022.1098133
  5. Otitis media: recent advances in otitis media vaccine development and model systems.
    Zahid A, Wilson JC, Grice ID, Peak IR. · · 2024 · cited 11× · PMID 38328427 · DOI 10.3389/fmicb.2024.1345027
  6. Panel 8: Vaccines and immunology.
    Alderson MR, Murphy T, Pelton SI, Novotny LA, et al · · 2020 · cited 6× · PMID 31948716 · DOI 10.1016/j.ijporl.2019.109839
  7. A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial.
    Arora AK, Chinsky K, Keller C, Mayers I, et al · · 2022 · cited 5× · PMID 36068109 · DOI 10.1016/j.vaccine.2022.08.053
  8. The COPD Pipeline XXXVII.
    Gross N. · · 2018 · PMID 29629406 · DOI 10.15326/jcopdf.5.1.2017.0184

Verify or expand the search:

Other trials of NTHi Mcat investigational vaccine (GSK3277511A)

Trials testing the same drug.

Other recruiting trials for Respiratory Disorders

Currently open trials in the same condition.

Other GlaxoSmithKline trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03281876.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing