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

NCT05166889 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: D9180C000032023-503571-19-002021-003797-30
• Study Type: interventional
• Target: 1,132
• Locations: 21 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)

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Huntsville, Alabama, 35801, United States

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Mobile, Alabama, 36608, United States

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Montgomery, Alabama, 36106, United States

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Phoenix, Arizona, 85044, United States

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Bakersfield, California, 93301, United States

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Sacramento, California, 95821, United States

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Boynton Beach, Florida, 33435, United States

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Ormond Beach, Florida, 32174, United States

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Plantation, Florida, 33324, United States

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Meridian, Idaho, 83642, United States

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Evergreen Park, Illinois, 60805, United States

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Normal, Illinois, 61761, United States

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Iowa City, Iowa, 52242, United States

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Kansas City, Kansas, 66104, United States

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Baton Rouge, Louisiana, 70816, United States

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Zachary, Louisiana, 70791, United States

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Baltimore, Maryland, 21224, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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Missoula, Montana, 59808, United States

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Brick, New Jersey, 08724, United States

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New York, New York, 10037, United States

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The Bronx, New York, 10455, United States

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Charlotte, North Carolina, 28277, United States

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Durham, North Carolina, 27710, United States

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Gastonia, North Carolina, 28054, United States

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Fargo, North Dakota, 58104, United States

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DuBois, Pennsylvania, 15801, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Sayre, Pennsylvania, 18840, United States

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Rapid City, South Dakota, 57702, United States

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Franklin, Tennessee, 37067, United States

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Houston, Texas, 77022, United States

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Kingwood, Texas, 77339, United States

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Salt Lake City, Utah, 84108, United States

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Burlington, Vermont, 05401, United States

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Buenos Aires, C1121 ABE, Argentina

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CABA, C1425BEN, Argentina

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Ciudad de Buenos Aires, C1414AIF, Argentina

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Córdoba, X5003DCE, Argentina

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Mar del Plata, 7600, Argentina

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Mar del Plata, B7600GWV, Argentina

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Mendoza, M5500CCG, Argentina

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Quilmes, B1878FNR, Argentina

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San Fernando, B1646EBJ, Argentina

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San Juan Bautista, 1888, Argentina

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San Miguel de Tucumán, 4000, Argentina

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Brussels, 1000, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Namur, 5101, Belgium

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Dupnitsa, 2600, Bulgaria

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Haskovo, 6305, Bulgaria

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Kozloduy, 3320, Bulgaria

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Lovech, 5500, Bulgaria

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Petrich, 2850, Bulgaria

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Pleven, 5800, Bulgaria

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Rousse, 7002, Bulgaria

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Sliven, 8800, Bulgaria

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Sofia, 1000, Bulgaria

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Sofia, 1606, Bulgaria

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Troyan Municipality, 5600, Bulgaria

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Vratsa, 3000, Bulgaria

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Calgary, Alberta, T3E 7M8, Canada

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Edmonton, Alberta, T5A 4L8, Canada

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Sherwood Park, Alberta, T8L 0N2, Canada

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Kamloops, British Columbia, V2C 5T1, Canada

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Kelowna, British Columbia, V1Y 4N7, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Guelph, Ontario, N1H 6J2, Canada

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Markham, Ontario, L3T 0C8, Canada

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Stouffville, Ontario, L4A 1H2, Canada

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Winchester, Ontario, K0C 2K0, Canada

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Montreal, PQ, H3T 1E2, Canada

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Québec, Quebec, G1G 5X1, Canada

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Québec, Quebec, G1V 4G5, Canada

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Terrebonne, Quebec, J6V 2H2, Canada

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Brno, 625 00, Czechia

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Broumov, 55001, Czechia

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Jindřichův Hradec, 377 01, Czechia

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Liberec, 460 63, Czechia

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Olomouc, 779 00, Czechia

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Rokycany, 337 22, Czechia

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Aalborg, 9000, Denmark

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Hvidovre, 2650, Denmark

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København NV, 2400, Denmark

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Næstved, 4700, Denmark

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Roskilde, 4000, Denmark

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Vejle, 7100, Denmark

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Hämeenlinna, 13530, Finland

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Helsinki, 00290, Finland

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Kuopio, 70210, Finland

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Tampere, 33520, Finland

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Turku, 20100, Finland

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Turku, FI-20521, Finland

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Budapest, 1036, Hungary

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Debrecen, 4032, Hungary

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Edelény, 3780, Hungary

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Encs, 3860, Hungary

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Mosonmagyaróvár, 9200, Hungary

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Nyíregyháza-Sóstóhegy, 4481, Hungary

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Százhalombatta, 2440, Hungary

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Ahmedabad, 382415, India

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Belagavi, 590010, India

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Coimbatore, 641028, India

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Dehradun, 248001, India

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Hyderabad, 500038, India

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Jaipur, 302039, India

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Mohali, 160062, India

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Nagpur, 440012, India

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Nashik, 422007, India

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New Delhi, 110029, India

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Surat, 395009, India

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Thane, 401107, India

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Asahikawa-shi, 078-8510, Japan

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Chikushino-shi, 818-8502, Japan

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Chūōku, 103-0022, Japan

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Fujieda-shi, 426-8677, Japan

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Fukuoka, 819-8555, Japan

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Hamamatsu, 430-8525, Japan

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Hamamatsu, 431-3192, Japan

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Hiroshima, 734-8530, Japan

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Iizuka-shi, 820-8505, Japan

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Itabashi-ku, 173-8610, Japan

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Iwata-shi, 438-8550, Japan

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Joyo-shi, 610-0113, Japan

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Kagoshima, 890-8520, Japan

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Kanazawa, 920-8650, Japan

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Kawachinagano-shi, 586-8521, Japan

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Kitakyusyu-shi, 806-8501, Japan

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Kobe, 651-0072, Japan

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Koga-shi, 811-3195, Japan

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Kokubunji-shi, 185-0014, Japan

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Matsusaka-shi, 515-8544, Japan

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Mizunami-shi, 509-6134, Japan

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Nagaoka-shi, 940-8621, Japan

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Nagoya, 460-0001, Japan

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Obihiro, 080-0017, Japan

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Okayama, 700-8558, Japan

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Osaka, 531-0073, Japan

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Osaka, 543-8555, Japan

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Osaka, 545-8586, Japan

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Sakaishi, 590-0064, Japan

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Shinjuku-ku, 162-8655, Japan

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Shizuoka, 420-8630, Japan

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Toshima-ku, 170-0003, Japan

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Toyonaka-shi, 560-8552, Japan

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Yanagawa-shi, 832-0059, Japan

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Yokohama, 221-0855, Japan

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Yokohama, 223-0059, Japan

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Yokohama, 232-0024, Japan

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Benito Juárez, 03650, Mexico

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Chihuahua City, 31000, Mexico

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Guadalajara, 44100, Mexico

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Guadalajara, 44200, Mexico

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Mexico City, 0 3100, Mexico

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Mérida, 97070, Mexico

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Monterrey, 64460, Mexico

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Morelia, 58000, Mexico

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Oaxaca City, 68020, Mexico

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Veracruz, 91910, Mexico

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Alkmaar, 1815 JD, Netherlands

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Eindhoven, 5623EJ, Netherlands

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Groningen, 9713 GZ, Netherlands

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Harderwijk, 3844 DG, Netherlands

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Heerlen, 6419 PC, Netherlands

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Zutphen, 7207 AE, Netherlands

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Zwolle, 8025 AB, Netherlands

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Ålesund, 6017, Norway

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Bergen, 5021, Norway

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Bodø, 8092, Norway

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Levanger, 7600, Norway

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Lørenskog, 1478, Norway

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Oslo, 0450, Norway

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Tønsberg, 3103, Norway

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Guimarães, 4835-235, Portugal

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Lisbon, 1769-001, Portugal

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Lisbon, 1998-018, Portugal

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Matosinhos Municipality, 4454-509, Portugal

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Vila Franca de Xira, 2600-009, Portugal

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Vila Nova de Gaia, 4434-502, Portugal

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Guaynabo, 00968, Puerto Rico

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Daegu, 42415, South Korea

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Incheon, 21431, South Korea

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Jeonju, 54907, South Korea

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Seoul, 03722, South Korea

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Seoul, 05030, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Seoul, 07061, South Korea

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Galdakao, 48960, Spain

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Madrid, 28040, Spain

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Málaga, 29010, Spain

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Mérida, 06800, Spain

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Pozuelo de Alarcón, 28223, Spain

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Santander, 39008, Spain

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Valencia, 46010, Spain

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Zaragoza, 50009, Spain

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Gothenburg, 413 45, Sweden

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Gothenburg, 413 46, Sweden

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Lund, 222 22, Sweden

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Malmo, 205 02, Sweden

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Stockholm, 11239, Sweden

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Ankara, 06620, Turkey (Türkiye)

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Aydin, 09100, Turkey (Türkiye)

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Istanbul, 34069, Turkey (Türkiye)

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Izmir, 35040, Turkey (Türkiye)

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Izmir, 35965, Turkey (Türkiye)

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Mersin, 33343, Turkey (Türkiye)

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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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 9, 2021
• First Posted: December 22, 2021
• Study Start: January 3, 2022
• Primary Completion: January 19, 2026
• Study Completion: March 11, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

SE (5); TU (6); BU (12); US (36); IN (12); JP (37); PT (6); CZ (6); DK (6); AR (11); HU (7); NO (7); KR (8); VN (2); PR (1); FI (6); ME (10); ES (8); CA (14); BE (5); NL (7)