Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations.

NCT05158387 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: D9180C000042021-003771-34
• Study Type: interventional
• Target: 1,172
• Locations: 20 countries
• Sites: 212

Brief Summary

The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab Dose 1 and Dose 2 administered subcutaneously (SC) in adult participants with symptomatic COPD and history of ≥ 2 moderate or ≥ 1 severe exacerbation of COPD in the previous 12 months. Participants should be receiving optimised treatment with maintenance inhaled therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) in stable doses throughout at least 3 months prior to enrolment.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Chronic Obstructive Pulmonary Disease; COPD; tozorakimab; exacerbations; ICS; LABA/LAMA

Outcome Measures

Primary Outcomes (1)

• Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.

  The primary endpoint will be assessed first in the primary population (former smokers with symptomatic COPD and a history of exacerbations, on optimised treatment with maintenance inhaled therapy \[triple therapy, or dual therapy if triple is not considered appropriate\]) and then assessed in the overall population of participants.

  over 52 weeks

Secondary Outcomes (21)

• Annualized rate of moderate to severe COPD exacerbations in former or current smokers.

  over 52 weeks

• Time to first moderate to severe COPD exacerbation in former smokers.

  over 52 weeks

• Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers.

  Week 52, or over 52 weeks

• Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in the overall population of current and former smokers.

  Week 52, or over 52 weeks

• Percentage of responders achieving MCID in E-RS:COPD total score in former smokers

  Week 52

Study Arms (3)

Tozorakimab Dose 1

EXPERIMENTAL

Dosing subcutaneously tozorakimab Dose 1 and placebo

Drug: Tozorakimab

Tozorakimab Dose 2

EXPERIMENTAL

Dosing subcutaneously tozorakimab Dose 2

Drug: Tozorakimab

Placebo

PLACEBO COMPARATOR

Dosing subcutaneously with equivalent volume to tozorakimab

Drug: Placebo

Interventions

Tozorakimab DRUG

Administered subcutaneously tozorakimab Dose 1 and placebo through Week 52.

Tozorakimab Dose 1

Placebo DRUG

Placebo administered subcutaneously, equivalent volume to tozorakimab through week 52.

Placebo

Eligibility Criteria

• Age: 40 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 40 years of age and capable of giving signed informed consent.
• Documented diagnosis of COPD for at least one year prior to enrolment.
• Post BD FEV1/FVC \< 0.70 and post-BD FEV1 \>20% of predicted normal value.
• Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment.
• Documented optimized inhaled dual or triple therapy at a stable dose for at least 3 months prior to enrolment.
• Smoking history of ≥ 10 pack-years.
• CAT total score ≥10, with each of the phlegm (sputum) and cough items with a score ≥ 2

You may not qualify if:

• Clinically important pulmonary disease other than COPD.
• Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms.
• Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
• Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that could affect safety, study findings or participants ability to complete the study.
• COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.
• Active significant infection within the 4 weeks prior to randomization, pneumonia within 6 weeks prior to randomization, or medical condition that predisposes the participant to infection.
• Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
• Significant COVID-19 illness within the 6 months prior to enrolment.
• Unstable cardiovascular disorder.
• Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
• History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.
• History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)
• Evidence of active liver disease, including jaundice during screening.
• Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms.
• Participants who have evidence of active TB.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (212)

Research Site

Sheffield, Alabama, 35660, United States

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Lincoln, California, 95648, United States

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Newport Beach, California, 92663, United States

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Northridge, California, 91324, United States

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Colorado Springs, Colorado, 80909, United States

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Newark, Delaware, 19713, United States

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Bay Pines, Florida, 33744, United States

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Cape Coral, Florida, 33990, United States

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Pensacola, Florida, 32503, United States

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Tampa, Florida, 33607, United States

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Winter Park, Florida, 32789, United States

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Macon, Georgia, 31201, United States

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Greenwood, Indiana, 46143, United States

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Bowling Green, Kentucky, 42101, United States

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White Marsh, Maryland, 21162, United States

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North Dartmouth, Massachusetts, 02747, United States

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Ann Arbor, Michigan, 48109, United States

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Farmington Hills, Michigan, 48336, United States

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Grand Rapids, Michigan, 49546, United States

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Buffalo, New York, 14203, United States

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The Bronx, New York, 10459, United States

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Toledo, Ohio, 43617, United States

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Oklahoma City, Oklahoma, 73104, United States

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Tulsa, Oklahoma, 74133, United States

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Philadelphia, Pennsylvania, 19140, United States

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Rock Hill, South Carolina, 29732, United States

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Amarillo, Texas, 79106, United States

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Boerne, Texas, 78006, United States

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Fort Worth, Texas, 76104, United States

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McKinney, Texas, 75069, United States

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Tomball, Texas, 77375, United States

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Webster, Texas, 77598, United States

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Williamsburg, Virginia, 23188, United States

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Cudahy, Wisconsin, 53110, United States

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Campbelltown, 2560, Australia

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Frankstown, 3199, Australia

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Macquarie University, 2109, Australia

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Melbourne, 3000, Australia

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Nedlands, 6009, Australia

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Southport, 4215, Australia

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Spearwood, 6163, Australia

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Wollongong, 2500, Australia

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Woodville South, 5011, Australia

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Blumenau, 89030-101, Brazil

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Botucatu, 18618-686, Brazil

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Brasília, 71681-603, Brazil

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Curitiba, 80440-220, Brazil

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Porto Alegre, 90035074, Brazil

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Porto Alegre, 9061-000, Brazil

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Porto Alegre, 91010-006, Brazil

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Rio de Janeiro, 22061-080, Brazil

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São Bernardo do Campo, 09750-420, Brazil

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São Paulo, 01323-903, Brazil

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São Paulo, 01409-001, Brazil

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São Paulo, 05403-000, Brazil

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Curicó, 3341643, Chile

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Santiago, 7500010, Chile

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Santiago, 7500657, Chile

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Santiago, 7500698, Chile

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Santiago, 8150000, Chile

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Santiago, 8241479, Chile

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Talca, 3465584, Chile

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Baotou, 014010, China

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Beijing, 100144, China

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Beijing, 101200, China

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Changchun, 130021, China

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Changde, 415000, China

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Changsha, 410015, China

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Chengdu, 610000, China

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Chengdu, 610031, China

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Chengdu, 610083, China

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Chongqing, 400013, China

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Chongqing, 400037, China

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Guangzhou, 510120, China

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Guangzhou, 510180, China

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Guangzhou, 510630, China

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Haikou, 570311, China

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Hangzhou, 310006, China

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Hefei, 230001, China

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Hohhot, 010010, China

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Kunming, 650032, China

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Linhai, 317000, China

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Nanchang, 330006, China

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Nanjing, 210006, China

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Ningbo, 315010, China

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Shanghai, 200002, China

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Shanghai, 200433, China

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Shanghai, 201199, China

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Shengyang, 110004, China

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Shenyang, 110016, China

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Shenzhen, 518020, China

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Shenzhen, 518053, China

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Shijiazhuang, 50051, China

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Suzhou, 215002, China

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Taiyuan, 030001, China

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Tianjin, 300050, China

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Wuhan, 430022, China

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Wuxi, 214023, China

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Xiamen, 361004, China

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Xuzhou, 221000, China

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Xuzhou, 221009, China

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Yangzhou, 225001, China

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Yinchuan, 750004, China

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Zhanjiang, 524004, China

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Zunyi, 563100, China

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Barranquilla, 80007, Colombia

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Ibague, 730006, Colombia

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Rionegro, 054047, Colombia

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Zipaquirá, 200251, Colombia

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Brest, 29609, France

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Dijon, 21079, France

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Grenoble, 38043, France

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Lyon, 69317, France

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Marseille, 13915, France

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Montivilliers, 76290, France

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Montpellier, 34090, France

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Pessac, 33604, France

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Saint-Herblain, 44093, France

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Toulouse, 31059, France

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Ahrensburg, 22926, Germany

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Bamberg, 96049, Germany

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Berlin, 10717, Germany

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Berlin, 12157, Germany

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Cologne, 51069, Germany

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Darmstadt, 64283, Germany

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Halle, 6108, Germany

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Marburg, 35037, Germany

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München, 80336, Germany

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München-Pasing, 81241, Germany

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Peine, 31224, Germany

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Alexandroupoli, 68100, Greece

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Athens, 11527, Greece

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Exohi Thessaloniki, 57010, Greece

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Ioannina, 45500, Greece

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Pátrai, 26500, Greece

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Thessaloniki, 57010, Greece

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Ashkelon, 78278, Israel

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Beersheba, 8410101, Israel

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Jerusalem, 9372212, Israel

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Kfar Saba, 4428164, Israel

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Rehovot, 76100, Israel

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Tel Aviv, 6423906, Israel

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Bari, 70124, Italy

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Massa, 54100, Italy

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Milan, 20142, Italy

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Milan, 20157, Italy

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Naples, 80131, Italy

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Roma, 00168, Italy

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Salerno, 84131, Italy

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San Donà di Piave, 30027, Italy

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Sassari, 07100, Italy

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Statte, 74010, Italy

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Telese Terme, 82037, Italy

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Tradate, 21049, Italy

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Vercelli, 13100, Italy

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Verona, 37134, Italy

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Lima, 15036, Peru

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Lima, 15046, Peru

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Lima, 15088, Peru

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Lima, LIMA 21, Peru

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Baguio City, 2600, Philippines

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Cebu City, 6000, Philippines

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Iloilo City, 5000, Philippines

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Bialystok, 15-044, Poland

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Bialystok, 15-704, Poland

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Bychawa, 23100, Poland

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Bydgoszcz, 85-796, Poland

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Katowice, 40-648, Poland

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Krakow, 30-033, Poland

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Lublin, 20-412, Poland

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Ostrowiec Świętokrzyski, 27-400, Poland

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Ostróda, 14-100, Poland

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Poznan, 60-693, Poland

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Poznan, 61-578, Poland

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Rzeszów, 35-205, Poland

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Skierniewice, 96-100, Poland

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Sosnowiec, 41-208, Poland

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Wroclaw, 53-301, Poland

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Ponce, 00717, Puerto Rico

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Brasov, 500283, Romania

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Bucharest, 050159, Romania

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Cluj-Napoca, 400371, Romania

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Constanța, 900002, Romania

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Timișoara, 300002, Romania

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Penza, 440067, Russia

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Saratov, 410012, Russia

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Hsinchu, 300, Taiwan

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Kaohsiung City, 807, Taiwan

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Kaohsiung City, 82445, Taiwan

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Taichung, 40443, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 100, Taiwan

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Taipei, 110, Taiwan

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Taoyuan District, 333, Taiwan

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Yunlin, 640, Taiwan

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Bang Kra So, 11000, Thailand

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Bangkok, 10700, Thailand

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Hat Yai, 90110, Thailand

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Khon Kaen, 40002, Thailand

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Muang,, 55000, Thailand

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Muang, 22000, Thailand

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Mueang, 20000, Thailand

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Nakhon Ratchasima, 30000, Thailand

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Bradford, BD9 6RJ, United Kingdom

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Corby, NN17 2UR, United Kingdom

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Corby, NN18 9EZ, United Kingdom

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Enfield, EN3 4GS, United Kingdom

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Hampshire, SO16 6YD, United Kingdom

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High Wycombe, HP11 2QW, United Kingdom

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Northwood, HA6 2RN, United Kingdom

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Preston, PR2 9QB, United Kingdom

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Shipley, BD18 3SA, United Kingdom

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MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: unblinded administrator/pharmacist
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: December 15, 2021
• Study Start: February 7, 2022
• Primary Completion: January 19, 2026
• Study Completion: March 22, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

DE (11); RO (5); PR (1); FR (10); US (34); RU (2); GR (6); TH (8); CN (43); IT (14); AU (9); PE (4); CO (4); IL (6); GB (9); PH (3); TW (9); BR (12); PL (15); CL (7)