OBERON: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tozorakimab Dose 1 Dosing subcutaneously tozorakimab Dose 1 and placebo |
Drug: Tozorakimab
Administered subcutaneously tozorakimab Dose 1 and placebo through Week 52.
|
| Experimental: Tozorakimab Dose 2 Dosing subcutaneously tozorakimab Dose 2 |
Drug: Tozorakimab
Administered subcutaneously tozorakimab Dose 2 through Week 52.
|
| Placebo Comparator: Placebo Dosing subcutaneously with equivalent volume to tozorakimab |
Drug: Placebo
Placebo administered subcutaneously, equivalent volume to tozorakimab through week 52.
|
Outcome Measures
Primary Outcome Measures
- Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers. [over 52 weeks]
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.
Secondary Outcome Measures
- Annualized rate of moderate to severe COPD exacerbations in former or current smokers. [over 52 weeks]
The annualized rate will be assessed in the overall population of participants including current and former smokers with symptomatic COPD and history of exacerbations, on optimised treatment with maintenance inhaled therapy.
- Time to first moderate to severe COPD exacerbation in former smokers. [over 52 weeks]
To explore the extent to which treatment with each dose of tozorakimab delays the time to first exacerbation compared with placebo in former smokers.
- Mean change from baseline in pre-BD, pre-dose trough FEV1 (mL) in former smokers. [Week 52, or over 52 weeks]
Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers.
- 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]
Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers.
- Percentage of responders achieving MCID in E-RS:COPD total score in former smokers. [Week 52]
Responder analyses for E-RS:COPD total score at Week 52 based upon a ≥ 2 point improvement (decrease) from baseline in former smokers.
- Percentage of responders achieving MCID in E-RS:COPD total score in the overall population of current and former smokers. [Week 52]
Responder analyses for E-RS:COPD total score at Week 52 based upon a ≥ 2 point improvement (decrease) from baseline in the overall population of current and former smokers.
- Mean change from baseline in E-RS:COPD total score in former smokers. [over 52 weeks]
Difference in mean change in E-RS:COPD total score from baseline in former smokers.
- Mean change from baseline in E-RS:COPD total score in the overall population of current and former smokers. [over 52 weeks]
Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers.
- Percentage of responders achieving MCID in SGRQ total score in former smokers. [Week 52]
Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline in former smokers.
- Percentage of responders achieving MCID in SGRQ total score in the overall population of current and former smokers. [Week 52]
Percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline in the overall population of current and former smokers.
- Mean change from baseline in SGRQ total score from in former smokers. [over 52 weeks]
Difference in mean change from baseline in SGRQ total score in former smokers.
- Mean change from baseline in SGRQ total score from in the overall population of current and former smokers [over 52 weeks]
Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers.
- Time to first severe COPD exacerbation in former smokers. [over 52 weeks]
To evaluate hazard ratio of first severe COPD exacerbation in former smokers.
- Annualized rate of severe COPD exacerbations in former smokers. [over 52 weeks]
The rate ratio of severe COPD exacerbations will be assessed in former smokers.
- Change from baseline in CAT total score. [Week 52]
Analyses of change from baseline in CAT total score in former smokers.
- Percentage of participants with a decrease in CAT total score in former smokers. [Week 52]
Proportion of participants achieving MCID in CAT total score, a decrease in CAT total score of ≥ 2 points from baseline in former smokers.
- Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers. [over 52 weeks]
Proportion of participants having ≥ 1 healthcare resource utilization type in former smokers.
- Annualized rate of healthcare resource utilization in former smokers. [over 52 weeks]
Annualized rate of healthcare resource utilization in former smokers.
- The change from baseline in mean number of puffs per day in rescue use in former smokers. [over 52 weeks]
Difference in mean number of puffs per day from baseline.
- Trough serum concentrations of tozorakimab. [over 52 weeks]
Pharmacokinetics: concentrations of tozorakimab in trough serum.
- Presence of anti-drug antibodies. [over 60 weeks]
Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant must be ≥ 40 years of age and capable of giving signed informed consent.
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Documented diagnosis of COPD for at least one year prior to enrolment.
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Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value.
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Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment.
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Documented optimized inhaled dual or triple therapy at a stable dose for at least 3 months prior to enrolment.
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Smoking history of ≥ 10 pack-years.
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CAT total score ≥10, with each of the phlegm (sputum) and cough items with a score ≥
Exclusion Criteria:
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Clinically important pulmonary disease other than COPD.
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Radiological findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms.
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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.
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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.
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COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.
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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.
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Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
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Significant COVID-19 illness within the 6 months prior to enrolment.
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Unstable cardiovascular disorder.
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Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
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History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV
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History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C).
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Evidence of active liver disease, including jaundice during screening.
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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.
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Participants who have evidence of active TB.
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Participants that have previously received tozorakimab.
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Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of their participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.
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Active vaping of any products within the 6 months prior to randomization and during the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Mobile | Alabama | United States | 36608 |
| 2 | Research Site | Montgomery | Alabama | United States | 36106 |
| 3 | Research Site | Phoenix | Arizona | United States | 85051 |
| 4 | Research Site | Bakersfield | California | United States | 93301 |
| 5 | Research Site | Palm Springs | California | United States | 92262 |
| 6 | Research Site | Sacramento | California | United States | 95821 |
| 7 | Research Site | Boynton Beach | Florida | United States | 33435 |
| 8 | Research Site | Jacksonville | Florida | United States | 32209 |
| 9 | Research Site | Kissimmee | Florida | United States | 34744 |
| 10 | Research Site | Ormond Beach | Florida | United States | 32174 |
| 11 | Research Site | Plantation | Florida | United States | 33324 |
| 12 | Research Site | Brookhaven | Georgia | United States | 30329 |
| 13 | Research Site | Meridian | Idaho | United States | 83642 |
| 14 | Research Site | Chicago | Illinois | United States | 60608 |
| 15 | Research Site | Evanston | Illinois | United States | 60201 |
| 16 | Research Site | Evergreen Park | Illinois | United States | 60805 |
| 17 | Research Site | Normal | Illinois | United States | 61761 |
| 18 | Research Site | Iowa City | Iowa | United States | 52242 |
| 19 | Research Site | Kansas City | Kansas | United States | 66104 |
| 20 | Research Site | Baton Rouge | Louisiana | United States | 70816 |
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| 22 | Research Site | Baltimore | Maryland | United States | 21224 |
| 23 | Research Site | Rochester | Minnesota | United States | 55905 |
| 24 | Research Site | Saint Louis | Missouri | United States | 63110 |
| 25 | Research Site | Saint Louis | Missouri | United States | 63141 |
| 26 | Research Site | Missoula | Montana | United States | 59808 |
| 27 | Research Site | Bronx | New York | United States | 10455 |
| 28 | Research Site | Buffalo | New York | United States | 14215 |
| 29 | Research Site | New Hyde Park | New York | United States | 11042 |
| 30 | Research Site | New York | New York | United States | 10036 |
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| 32 | Research Site | North Massapequa | New York | United States | 11758 |
| 33 | Research Site | Charlotte | North Carolina | United States | 28277 |
| 34 | Research Site | Durham | North Carolina | United States | 27710 |
| 35 | Research Site | Gastonia | North Carolina | United States | 28054 |
| 36 | Research Site | Raleigh | North Carolina | United States | 27607 |
| 37 | Research Site | Fargo | North Dakota | United States | 58104 |
| 38 | Research Site | DuBois | Pennsylvania | United States | 15801 |
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| 42 | Research Site | Rapid City | South Dakota | United States | 57702 |
| 43 | Research Site | Franklin | Tennessee | United States | 37067 |
| 44 | Research Site | Nashville | Tennessee | United States | 37232 |
| 45 | Research Site | Fort Worth | Texas | United States | 76107 |
| 46 | Research Site | Houston | Texas | United States | 77022 |
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| 48 | Research Site | Salt Lake City | Utah | United States | 84108 |
| 49 | Research Site | Colchester | Vermont | United States | 05446 |
| 50 | Research Site | Charleston | West Virginia | United States | 25304 |
| 51 | Research Site | Buenos Aires | Argentina | C1121 ABE | |
| 52 | Research Site | Buenos Aires | Argentina | C1414AIF | |
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| 54 | Research Site | Córdoba | Argentina | X5003DCE | |
| 55 | Research Site | Florencio Varela | Argentina | 1888 | |
| 56 | Research Site | Mar del Plata | Argentina | 7600 | |
| 57 | Research Site | Mar del Plata | Argentina | B7600GWV | |
| 58 | Research Site | Mendoza | Argentina | M5500GIP | |
| 59 | Research Site | Ranelagh | Argentina | 1886 | |
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| 61 | Research Site | Tucumán | Argentina | 4000 | |
| 62 | Research Site | Bruxelles | Belgium | 1000 | |
| 63 | Research Site | Gent | Belgium | 9000 | |
| 64 | Research Site | Leuven | Belgium | 3000 | |
| 65 | Research Site | Liege | Belgium | 4000 | |
| 66 | Research Site | Namur | Belgium | 5101 | |
| 67 | Research Site | Dupnitsa | Bulgaria | 2600 | |
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| 90 | Research Site | Quebec | Canada | G1V 4G5 | |
| 91 | Research Site | Brno | Czechia | 625 00 | |
| 92 | Research Site | Broumov | Czechia | 55001 | |
| 93 | Research Site | Jihlava | Czechia | 586 33 | |
| 94 | Research Site | Jindrichuv Hradec | Czechia | 377 01 | |
| 95 | Research Site | Liberec 1 | Czechia | 460 63 | |
| 96 | Research Site | Mlada Boleslav | Czechia | 293 01 | |
| 97 | Research Site | Olomouc | Czechia | 779 00 | |
| 98 | Research Site | Rokycany | Czechia | 337 22 | |
| 99 | Research Site | Aarhus | Denmark | 8200 | |
| 100 | Research Site | Hvidovre | Denmark | 2650 | |
| 101 | Research Site | København NV | Denmark | 2400 | |
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| 106 | Research Site | Helsinki | Finland | 00290 | |
| 107 | Research Site | Hämeenlinna | Finland | 13530 | |
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| 109 | Research Site | Tampere | Finland | 33520 | |
| 110 | Research Site | Turku | Finland | 20100 | |
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| 112 | Research Site | Baja | Hungary | 6500 | |
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| 118 | Research Site | Százhalombatta | Hungary | 2440 | |
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| 120 | Research Site | Belagavi | India | 590010 | |
| 121 | Research Site | Coimbatore | India | 641028 | |
| 122 | Research Site | Dehradun | India | 248001 | |
| 123 | Research Site | Jaipur | India | 302039 | |
| 124 | Research Site | Kolkatta | India | 700027 | |
| 125 | Research Site | Mohali | India | 160062 | |
| 126 | Research Site | Nagpur | India | 440012 | |
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| 128 | Research Site | Nashik | India | 422007 | |
| 129 | Research Site | New Delhi | India | 110017 | |
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| 131 | Research Site | Chuo-ku | Japan | 103-0022 | |
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| 134 | Research Site | Kawachinagano-shi | Japan | 586-8521 | |
| 135 | Research Site | Kiyose-shi | Japan | 204-8585 | |
| 136 | Research Site | Koga-shi | Japan | 811-3195 | |
| 137 | Research Site | Kokubunji-shi | Japan | 185-0014 | |
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| 140 | Research Site | Obihiro | Japan | 080-0017 | |
| 141 | Research Site | Osaka-shi | Japan | 531-0073 | |
| 142 | Research Site | Sakaide-shi | Japan | 762-0031 | |
| 143 | Research Site | Tachikawa-shi | Japan | 190-0014 | |
| 144 | Research Site | Toshima-ku | Japan | 170-0003 | |
| 145 | Research Site | Yokohama-shi | Japan | 223-0059 | |
| 146 | Research Site | Daegu | Korea, Republic of | 42415 | |
| 147 | Research Site | Incheon | Korea, Republic of | 21431 | |
| 148 | Research Site | Jeonju-si | Korea, Republic of | 54907 | |
| 149 | Research Site | Seoul | Korea, Republic of | 03722 | |
| 150 | Research Site | Seoul | Korea, Republic of | 05030 | |
| 151 | Research Site | Seoul | Korea, Republic of | 05505 | |
| 152 | Research Site | Seoul | Korea, Republic of | 06591 | |
| 153 | Research Site | Seoul | Korea, Republic of | 07061 | |
| 154 | Research Site | Benito Juarez | Mexico | 03650 | |
| 155 | Research Site | Chihuahua | Mexico | 31000 | |
| 156 | Research Site | Guadalajara | Mexico | 44100 | |
| 157 | Research Site | Guadalajara | Mexico | 44200 | |
| 158 | Research Site | Mexico City | Mexico | 0 3100 | |
| 159 | Research Site | Monterrey | Mexico | 64460 | |
| 160 | Research Site | Morelia | Mexico | 58000 | |
| 161 | Research Site | Mérida | Mexico | 97070 | |
| 162 | Research Site | Oaxaca | Mexico | 68020 | |
| 163 | Research Site | Veracruz | Mexico | 91910 | |
| 164 | Research Site | Alkmaar | Netherlands | 1815 JD | |
| 165 | Research Site | Eindhoven | Netherlands | 5623EJ | |
| 166 | Research Site | Groningen | Netherlands | 9713 GZ | |
| 167 | Research Site | Harderwijk | Netherlands | 3844 DG | |
| 168 | Research Site | Heerlen | Netherlands | 6419 PC | |
| 169 | Research Site | Zutphen | Netherlands | 7207 AE | |
| 170 | Research Site | Zwolle | Netherlands | 8025 AB | |
| 171 | Research Site | Bergen | Norway | 5021 | |
| 172 | Research Site | Bodø | Norway | 8092 | |
| 173 | Research Site | Levanger | Norway | 7600 | |
| 174 | Research Site | Lørenskog | Norway | 1478 | |
| 175 | Research Site | Oslo | Norway | 0450 | |
| 176 | Research Site | Tønsberg | Norway | 3103 | |
| 177 | Research Site | Lisboa | Portugal | 1769-001 | |
| 178 | Research Site | Lisboa | Portugal | 1998-018 | |
| 179 | Research Site | Galdakao | Spain | 48960 | |
| 180 | Research Site | Madrid | Spain | 28040 | |
| 181 | Research Site | Malaga | Spain | 29010 | |
| 182 | Research Site | Mérida | Spain | 06800 | |
| 183 | Research Site | Pozuelo de Alarcon | Spain | 28223 | |
| 184 | Research Site | Santander | Spain | 39008 | |
| 185 | Research Site | Valencia | Spain | 46010 | |
| 186 | Research Site | Zaragoza | Spain | 50009 | |
| 187 | Research Site | Göteborg | Sweden | 413 46 | |
| 188 | Research Site | Göteborg | Sweden | 41345 | |
| 189 | Research Site | Lund | Sweden | 222 22 | |
| 190 | Research Site | Malmö | Sweden | 205 02 | |
| 191 | Research Site | Stockholm | Sweden | 11239 | |
| 192 | Research Site | Örebro | Sweden | 70185 | |
| 193 | Research Site | Ankara | Turkey | 06620 | |
| 194 | Research Site | Aydin | Turkey | 09100 | |
| 195 | Research Site | Istanbul | Turkey | 34069 | |
| 196 | Research Site | Istanbul | Turkey | ||
| 197 | Research Site | Izmir | Turkey | 35040 | |
| 198 | Research Site | Mersin | Turkey | 33343 | |
| 199 | Research Site | Hanoi | Vietnam | 100000 | |
| 200 | Research Site | Ho Chi Minh | Vietnam | 700000 |
Sponsors and Collaborators
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D9180C00003
- 2021-003797-30