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.

NCT03281876 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2074892017-000880-34
• Study Type: interventional
• Target: 606
• Locations: 8 countries
• Sites: 67

Brief 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.

Conditions

Respiratory Disorders

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (31)

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

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

• Number of Subjects Reported With Each Solicited General AE

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

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

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

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

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

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

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

Study Arms (2)

GSK3277511A Group

EXPERIMENTAL

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)

CONTROL Group

PLACEBO COMPARATOR

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

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.

GSK3277511A Group

Placebo BIOLOGICAL

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

CONTROL Group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (67)

GSK Investigational Site

Mesa, Arizona, 85213, United States

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GSK Investigational Site

Phoenix, Arizona, 85018, United States

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GSK Investigational Site

Phoenix, Arizona, 85020, United States

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GSK Investigational Site

Palm Springs, California, 92262, United States

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GSK Investigational Site

Clearwater, Florida, 33765, United States

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GSK Investigational Site

Jacksonville, Florida, 32205, United States

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GSK Investigational Site

Jacksonville, Florida, 32216, United States

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GSK Investigational Site

Council Bluffs, Iowa, 51503, United States

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GSK Investigational Site

Wichita, Kansas, 67207, United States

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GSK Investigational Site

Missoula, Montana, 59808, United States

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GSK Investigational Site

Neptune City, New Jersey, 07753, United States

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GSK Investigational Site

Charlotte, North Carolina, 28207, United States

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GSK Investigational Site

Mooresville, North Carolina, 28117, United States

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GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

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GSK Investigational Site

Columbus, Ohio, 43213, United States

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GSK Investigational Site

Corvallis, Oregon, 97330, United States

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GSK Investigational Site

Medford, Oregon, 97504, United States

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GSK Investigational Site

Erie, Pennsylvania, 16508, United States

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GSK Investigational Site

Gaffney, South Carolina, 29340, United States

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GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

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GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

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GSK Investigational Site

Union, South Carolina, 29379, United States

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GSK Investigational Site

Abingdon, Virginia, 24210, United States

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GSK Investigational Site

Richmond, Virginia, 23225, United States

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GSK Investigational Site

Wenatchee, Washington, 98801, United States

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Genk, 3600, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Kortrijk, 8500, Belgium

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GSK Investigational Site

Leuven, 3000, Belgium

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GSK Investigational Site

Liège, 4000, Belgium

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GSK Investigational Site

Edmonton, Alberta, T6G 2G3, Canada

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GSK Investigational Site

Vancouver, British Columbia, V5Z 1M9, Canada

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GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

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GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

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GSK Investigational Site

Montreal, Quebec, H3T1E2, Canada

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GSK Investigational Site

Québec, Quebec, G1V 4G5, Canada

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GSK Investigational Site

Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

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GSK Investigational Site

Brest, 29609, France

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GSK Investigational Site

Créteil, 94010, France

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GSK Investigational Site

Marseille, 13285, France

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GSK Investigational Site

Montpellier, 34295, France

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GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

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GSK Investigational Site

Immenhausen, Hesse, 34376, Germany

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GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

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GSK Investigational Site

Lübeck, Schleswig-Holstein, 23552, Germany

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GSK Investigational Site

Magdeburg, 39120, Germany

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GSK Investigational Site

Cona (FE), Emilia-Romagna, 44124, Italy

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GSK Investigational Site

Parma, Emilia-Romagna, 43100, Italy

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GSK Investigational Site

Milan, Lombardy, 20122, Italy

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GSK Investigational Site

Milan, Lombardy, 20142, Italy

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GSK Investigational Site

Monza, Lombardy, 20900, Italy

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GSK Investigational Site

Negrar, Veneto, 37024, Italy

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GSK Investigational Site

Barcelona, 08003, Spain

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GSK Investigational Site

Centelles (Barcelona), 08540, Spain

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GSK Investigational Site

Elda, 03600, Spain

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GSK Investigational Site

La Roca Del Valles (Barcelona), 08430, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

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GSK Investigational Site

Vic, 28500, Spain

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GSK Investigational Site

Portsmouth, Hampshire, PO6 3LY, United Kingdom

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GSK Investigational Site

Bradford, BD9 6RJ, United Kingdom

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GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

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GSK Investigational Site

Edinburgh, EH16 4SA, United Kingdom

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GSK Investigational Site

High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom

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GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

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Related Publications (2)

• 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.

  PMID: 36068109 DERIVED

• 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.

  PMID: 35026180 DERIVED

MeSH Terms

Conditions

Respiration Disorders; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data will be collected in an observer-blind manner. By observer-blind, it is meant that during the course of the study, the vaccine recipient and those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity and efficacy) will all be unaware of whether vaccine or placebo was administered. Each study site is responsible for having a blinding plan. To work in an observer-blind manner, vaccine preparation and administration will be done by authorised medical personnel who will not participate in any of the study clinical evaluation assays. Two teams of study personnel will hence be set up: * A team of unblinded personnel (responsible for the preparation and the administration of the vaccines) * A team of blinded personnel (responsible for the clinical evaluation of the subjects).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase IIB, randomised, observer-blind, placebo-controlled, multi-centric study with two parallel groups.

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 13, 2017
• Study Start: November 27, 2017
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: January 11, 2021
• Results First Posted: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (25); CA (7); DE (6); IT (6); BE (6); GB (6); ES (7); FR (4)