AzTrials
AzTrials

Respiratory DisordersPhase 2NCT03281876

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 study testing NTHi Mcat investigational vaccine (GSK3277511A) in people with Respiratory Disorders, run by GlaxoSmithKline at 67 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Respiratory Disorders
What is being tested?
NTHi Mcat investigational vaccine (GSK3277511A)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
606 participants
Where
67 sitesin 8 countries
Study dates
27 Nov 2017to 26 Mar 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

67 sites in 8 countries.

67 sites in 8 countries

United States25 sites

  • GSK Investigational Site

    Abingdon, Virginia, 24210

  • GSK Investigational Site

    Charlotte, North Carolina, 28207

  • GSK Investigational Site

    Clearwater, Florida, 33765

  • GSK Investigational Site

    Columbus, Ohio, 43213

  • GSK Investigational Site

    Corvallis, Oregon, 97330

  • GSK Investigational Site

    Council Bluffs, Iowa, 51503

  • GSK Investigational Site

    Erie, Pennsylvania, 16508

  • GSK Investigational Site

    Gaffney, South Carolina, 29340

  • GSK Investigational Site

    Jacksonville, Florida, 32205

  • GSK Investigational Site

    Jacksonville, Florida, 32216

  • GSK Investigational Site

    Medford, Oregon, 97504

  • GSK Investigational Site

    Mesa, Arizona, 85213

  • GSK Investigational Site

    Missoula, Montana, 59808

  • GSK Investigational Site

    Mooresville, North Carolina, 28117

  • GSK Investigational Site

    Mt. Pleasant, South Carolina, 29464

  • GSK Investigational Site

    Neptune City, New Jersey, 07753

  • GSK Investigational Site

    Palm Springs, California, 92262

  • GSK Investigational Site

    Phoenix, Arizona, 85018

  • GSK Investigational Site

    Phoenix, Arizona, 85020

  • GSK Investigational Site

    Richmond, Virginia, 23225

  • GSK Investigational Site

    Spartanburg, South Carolina, 29303

  • GSK Investigational Site

    Union, South Carolina, 29379

  • GSK Investigational Site

    Wenatchee, Washington, 98801

  • GSK Investigational Site

    Wichita, Kansas, 67207

  • GSK Investigational Site

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada7 sites

  • GSK Investigational Site

    Edmonton, Alberta, T6G 2G3

  • GSK Investigational Site

    Halifax, Nova Scotia, B3K 6R8

  • GSK Investigational Site

    Montreal, Quebec, H3T1E2

  • GSK Investigational Site

    Québec, Quebec, G1V 4G5

  • GSK Investigational Site

    Saint-Charles-Borromée, Quebec, J6E 2B4

  • GSK Investigational Site

    Truro, Nova Scotia, B2N 1L2

  • GSK Investigational Site

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Spain7 sites

  • GSK Investigational Site

    Barcelona, 08003

  • GSK Investigational Site

    Centelles (Barcelona), 08540

  • GSK Investigational Site

    Elda, 03600

  • GSK Investigational Site

    La Roca Del Valles (Barcelona), 08430

  • GSK Investigational Site

    Madrid, 28007

  • GSK Investigational Site

    Pozuelo de Alarcón/Madrid, 28223

  • GSK Investigational Site

    Vic, 28500

Other trials in Spain

Belgium6 sites

  • GSK Investigational Site

    Brussels, 1000

  • GSK Investigational Site

    Genk, 3600

  • GSK Investigational Site

    Ghent, 9000

  • GSK Investigational Site

    Kortrijk, 8500

  • GSK Investigational Site

    Leuven, 3000

  • GSK Investigational Site

    Liège, 4000

Other trials in Belgium

Germany6 sites

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60389

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Großhansdorf, Schleswig-Holstein, 22927

  • GSK Investigational Site

    Immenhausen, Hesse, 34376

  • GSK Investigational Site

    Lübeck, Schleswig-Holstein, 23552

  • GSK Investigational Site

    Magdeburg, 39120

Other trials in Germany

Italy6 sites

  • GSK Investigational Site

    Cona (FE), Emilia-Romagna, 44124

  • GSK Investigational Site

    Milan, Lombardy, 20122

  • GSK Investigational Site

    Milan, Lombardy, 20142

  • GSK Investigational Site

    Monza, Lombardy, 20900

  • GSK Investigational Site

    Negrar, Veneto, 37024

  • GSK Investigational Site

    Parma, Emilia-Romagna, 43100

Other trials in Italy

United Kingdom6 sites

  • GSK Investigational Site

    Bradford, BD9 6RJ

  • GSK Investigational Site

    Dundee, DD1 9SY

  • GSK Investigational Site

    Edinburgh, EH16 4SA

  • GSK Investigational Site

    High Heaton, Newcastle Upon Tyne, NE7 7DN

  • GSK Investigational Site

    Portsmouth, Hampshire, PO6 3LY

  • GSK Investigational Site

    Southampton, SO16 6YD

Other trials in United Kingdom

France4 sites

  • GSK Investigational Site

    Brest, 29609

  • GSK Investigational Site

    Créteil, 94010

  • GSK Investigational Site

    Marseille, 13285

  • GSK Investigational Site

    Montpellier, 34295

Other trials in France

About this study

Official title: An Observer-blind Study to Evaluate the Efficacy, Safety, Reactogenicity and Immunogenicity of the GSK Biologicals' Investigational Vaccine GSK3277511A When Administered to COPD Patients

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.

Read more

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.
Being tested
NTHi Mcat investigational vaccine (GSK3277511A), Placebo
Keywords
Immunogenicity, Vaccination, Chronic Obstructive Pulmonary Disease, Non-typeable Haemophilus influenzae, Acute exacerbation of COPD, Moraxella catarrhalis, Efficacy, Safety
Medical subject headings
Respiration Disorders, Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NTHi Mcat investigational vaccine (GSK3277511A)Biological

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

  • PlaceboBiological

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

Study groups in NCT03281876
Study groupRoleWhat they receive
GSK3277511A GroupExperimentalHealthy 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.
Receives: Biological: NTHi Mcat investigational vaccine (GSK3277511A)
CONTROL GroupPlacebo comparatorHealthy males and females, 40 to 80 years of age, who received two doses of placebo vaccine at Day 1 and Day 61.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

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

Secondary outcomes (31)

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

    Assessed solicited local symptoms were pain, redness and swelling

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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).

    Measured: 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).

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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).

    Measured: 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).

    Measured: 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).

    Measured: 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.)

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: At Day 1, Day 91, Day 271 and at Day 451

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2017
  2. Study start27 Nov 2017
  3. Primary completion26 Mar 2020
  4. Study completion26 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase IIB, randomised, observer-blind, placebo-controlled, multi-centric study with two parallel groups.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
606 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03281876
Sponsor's protocol ID
207489
Other IDs
2017-000880-34, 2017
Status last verified
Jan 2021
First submitted
5 Sep 2017
Last updated
11 Jan 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

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.

    PubMed 35026180

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NTHi Mcat investigational vaccine (GSK3277511A) in people with Respiratory Disorders, run by GlaxoSmithKline at 67 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in United States, Canada, Spain, Belgium, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year (time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03281876, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2021.

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