A Phase 2 interventional study of Tezepelumab and Placebo in Chronic Obstructive Pulmonary Disease (COPD), sponsored by AstraZeneca. Completed at 91 sites in 10 countries. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-02-18.
Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving triple inhaled maintenance therapy, and having had 2 or more documented COPD exacerbations in the 12 months prior to Visit 1. Approximately, 338 subjects will be randomized globally. Subjects will be stratified by region and prior number of exacerbations (2 vs. 3 or more). Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52 week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.
4,131 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 697 are open to participants now.
This study's enrollment of 337 is above the median of 70 across 2,926 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.
Browse Pulmonary Disease, Chronic Obstructive studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Tezepelumab, SC, Q4W
Biological: Tezepelumab
Matching placebo, SC, Q4W
Other: Placebo
Tezepelumab subcutaneous injection
Placebo subcutaneous injection
Rate of Moderate or Severe COPD Exacerbations in Participants With Moderate to Very Severe COPD.
A COPD exacerbation was defined as a change in the participant's usual COPD symptoms that is beyond normal day-to-day variation, is acute in onset, lasts 2 or more days, and may warrant a change in regular medication and leads to any of the following: Use of systemic corticosteroids for at least 3 days, use of antibiotics for at least 3 days, an inpatient hospitalisation due to COPD, or results in death. Analysis was done using a negative binomial model with the response variable as the number of COPD exacerbations experienced during the follow-up for exacerbations. The model included covariates of treatment group, region, and number of exacerbations reported at randomisation as recorded in IWRS (2, \>=3). The logarithm of the time at risk (in years) for exacerbation in the study is used as an offset variable.
Time frame: From randomisation up to Week 52
Time to First Moderate/Severe COPD Exacerbation
Time to first moderate/severe COPD exacerbation post-randomisation, presented as number of subjects with at least one moderate/severe COPD exacerbation.
Time frame: From randomisation up to Week 52
Proportion of Participants COPD Exacerbation Free at Week 52
An exacerbation event was defined as described in primary analysis. A participant was exacerbation free if they did not experience any moderate or severe exacerbations from randomisation to Week 52 (EOT).
Time frame: From randomisation up to Week 52
Comparison of Annual Severe COPD Exacerbation Rates Over 52 Weeks
An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.
Time frame: From randomisation up to Week 52
Proportion of Participants With >=1 Severe COPD Exacerbations Over 52 Weeks
An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.
Time frame: From randomisation up to Week 52
Time to First Severe COPD Exacerbation
Time to first severe COPD exacerbation post-randomisation, presented as number of subjects with at least one severe COPD exacerbation.
Time frame: From randomisation up to Week 52
Least Square (LS) Mean Difference in Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 (FEV1) at Week 52
Pre-Bronchodilator FEV1 (L) was determined by spirometry at the clinic visit. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. Change from baseline was obtained as an absolute difference between Week 52 measure and the baseline value. Baseline was defined as the last assessment recorded prior to the first dose of study treatment.
Time frame: Baseline and Week 52
Lease Square (LS) Mean Difference in Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Baseline is the measurement recorded at Week 0 (Visit 3).
Time frame: Baseline and Week 52
Proportion of Participants Achieving a Minimum Clinically Important Difference of 4 Units or More in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. A responder was defined as an individual who had "improvement" at Week 52 (\>=4 point decrease in SGRQ total score).
Time frame: Baseline and Week 52
Least Square (LS) Mean Difference in Change From Baseline in COPD Assessment Tool (CAT) Total Score at Week 52
The CAT is an 8-item PRO developed to measure the impact of COPD on health status. A CAT total score is the sum of item responses. Scores range from 0-40 with higher scores indicative of greater COPD impact on health status. Baseline was defined as the value at the randomisation visit (Visit 3). If the Visit 3 measurement was missing, the screening value was used as baseline instead.
Time frame: Baseline and Week 52
Serum Concentration of Tezepelumab
Blood samples were collected to determine the serum concentration of Tezepelumab. With the exception of Week 0 and Week 64, only pre-dose data from samples collected between 21 and 35 days after previous dose of investigational product were included.
Time frame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab
Blood samples were measured for the presence of ADAs for tezepelumab using validated assays. Treatment-induced ADA positive was defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive was defined as baseline positive ADA titre that was boosted to a 4 fold or higher level following IP administration. TE-ADA positive was defined as the sum of treatment-induced ADA positive and treatment-boosted ADA positive. ADA incidence is the proportion of TE-ADA positive subjects in a population. ADA persistently positive was defined as ADA positive at \>= 2 post-baseline assessments or ADA positive at last post-baseline assessment. ADA transiently positive was defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of ADA persistently positive. Treatment-induced nAb positive was defined as nAb negative or ADA negative at baseline and nAb positive at any post-baseline visit.
Time frame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
The study was conducted at 80 centres in 10 countries. A total of 579 participants were screened of which 337 were randomised. Of the 337 randomised, 333 participants received treatment. 4 participants randomised in error and did not receive treatment. 187 participants not randomised were due to screen failures.
| Milestone | Tezepelumab | Placebo |
|---|---|---|
| Started | 169 | 168 |
| Received treatment | 165 | 168 |
| Completed treatment | 138 | 138 |
| Completed | 146 | 150 |
| Not completed | 23 | 18 |
| Withdrew: Withdrawal by subject | 8 | 11 |
| Withdrew: Lost to follow-up | 1 | 1 |
| Withdrew: Adverse event | 2 | 2 |
| Withdrew: Death | 2 | 4 |
| Withdrew: Site closure | 6 | 0 |
| Withdrew: Failure to meet randomisation criteria | 4 | 0 |
A COPD exacerbation was defined as a change in the participant's usual COPD symptoms that is beyond normal day-to-day variation, is acute in onset, lasts 2 or more days, and may warrant a change in regular medication and leads to any of the following: Use of systemic corticosteroids for at least 3 days, use of antibiotics for at least 3 days, an inpatient hospitalisation due to COPD, or results in death. Analysis was done using a negative binomial model with the response variable as the number of COPD exacerbations experienced during the follow-up for exacerbations. The model included covariates of treatment group, region, and number of exacerbations reported at randomisation as recorded in IWRS (2, \>=3). The logarithm of the time at risk (in years) for exacerbation in the study is used as an offset variable.
| exacerbations per year | Tezepelumab | Placebo |
|---|---|---|
| Rate of Moderate or Severe COPD Exacerbations in Participants With Moderate to Very Severe COPD. | 1.75 (1.45 to 2.11) | 2.11 (1.77 to 2.53) |
Time to first moderate/severe COPD exacerbation post-randomisation, presented as number of subjects with at least one moderate/severe COPD exacerbation.
| Participants | Tezepelumab | Placebo |
|---|---|---|
| Time to First Moderate/Severe COPD Exacerbation | 94 | 105 |
An exacerbation event was defined as described in primary analysis. A participant was exacerbation free if they did not experience any moderate or severe exacerbations from randomisation to Week 52 (EOT).
| Participants | Tezepelumab | Placebo |
|---|---|---|
| Proportion of Participants COPD Exacerbation Free at Week 52 | 71 | 63 |
An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.
| exacerbations per year | Tezepelumab | Placebo |
|---|---|---|
| Comparison of Annual Severe COPD Exacerbation Rates Over 52 Weeks | 0.13 (0.07 to 0.24) | 0.25 (0.15 to 0.42) |
An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.
| Participants | Tezepelumab | Placebo |
|---|---|---|
| Proportion of Participants With >=1 Severe COPD Exacerbations Over 52 Weeks | 16 | 22 |
Time to first severe COPD exacerbation post-randomisation, presented as number of subjects with at least one severe COPD exacerbation.
| Participants | Tezepelumab | Placebo |
|---|---|---|
| Time to First Severe COPD Exacerbation | 16 | 22 |
Pre-Bronchodilator FEV1 (L) was determined by spirometry at the clinic visit. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. Change from baseline was obtained as an absolute difference between Week 52 measure and the baseline value. Baseline was defined as the last assessment recorded prior to the first dose of study treatment.
| Liters | Tezepelumab | Placebo |
|---|---|---|
| Least Square (LS) Mean Difference in Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 (FEV1) at Week 52 | 0.026 ± 0.015 | -0.029 ± 0.015 |
The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Baseline is the measurement recorded at Week 0 (Visit 3).
| units on a scale | Tezepelumab | Placebo |
|---|---|---|
| Lease Square (LS) Mean Difference in Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | -4.796 ± 1.176 | -1.863 ± 1.189 |
The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. A responder was defined as an individual who had "improvement" at Week 52 (\>=4 point decrease in SGRQ total score).
| Participants | Tezepelumab | Placebo |
|---|---|---|
| Proportion of Participants Achieving a Minimum Clinically Important Difference of 4 Units or More in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 | 65 | 59 |
The CAT is an 8-item PRO developed to measure the impact of COPD on health status. A CAT total score is the sum of item responses. Scores range from 0-40 with higher scores indicative of greater COPD impact on health status. Baseline was defined as the value at the randomisation visit (Visit 3). If the Visit 3 measurement was missing, the screening value was used as baseline instead.
| units on a scale | Tezepelumab | Placebo |
|---|---|---|
| Least Square (LS) Mean Difference in Change From Baseline in COPD Assessment Tool (CAT) Total Score at Week 52 | -3.037 ± 0.524 | -1.182 ± 0.524 |
Blood samples were collected to determine the serum concentration of Tezepelumab. With the exception of Week 0 and Week 64, only pre-dose data from samples collected between 21 and 35 days after previous dose of investigational product were included.
| microgram per milliliter (mg/mL) | Tezepelumab | Placebo |
|---|---|---|
| Week 0 | NA ± NA | — |
| Week 4 | 25.881 ± 11.8828 | — |
| Week 12 | 44.316 ± 19.0716 | — |
| Week 24 | 49.093 ± 21.2414 | — |
| Week 36 | 48.667 ± 22.2241 | — |
| Week 52 | 52.659 ± 26.1703 | — |
| Follow-up Week 64 | 6.602 ± 6.1832 | — |
Blood samples were measured for the presence of ADAs for tezepelumab using validated assays. Treatment-induced ADA positive was defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive was defined as baseline positive ADA titre that was boosted to a 4 fold or higher level following IP administration. TE-ADA positive was defined as the sum of treatment-induced ADA positive and treatment-boosted ADA positive. ADA incidence is the proportion of TE-ADA positive subjects in a population. ADA persistently positive was defined as ADA positive at \>= 2 post-baseline assessments or ADA positive at last post-baseline assessment. ADA transiently positive was defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of ADA persistently positive. Treatment-induced nAb positive was defined as nAb negative or ADA negative at baseline and nAb positive at any post-baseline visit.
| Participants | Tezepelumab | Placebo |
|---|---|---|
| ADA positive at baseline and/or post-baseline (ADA prevalence) | 10 | 19 |
| Any baseline ADA positive | 5 | 8 |
| Only baseline ADA positive | 2 | 1 |
| Any post-baseline ADA positive | 8 | 18 |
| Both baseline and at least one post-baseline ADA positive | 3 | 7 |
| Treatment-induced ADA positive | 5 | 11 |
| Treatment-boosted ADA positive | 0 | 0 |
| TE-ADA positive (ADA incidence) | 5 | 11 |
| ADA persistently positive | 5 | 15 |
| ADA transiently positive | 3 | 3 |
| nAb positive at baseline and/or post-baseline (nAb prevalence) | 0 | 0 |
| Treatment-induced nAb positive (nAb incidence) | 0 | 0 |
Collected over From first dose of study drug until end of study at Week 64.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Teze 420 mg Q4W | 3/165 (1.8%) | 56/165 (33.9%) | 78/165 (47.3%) |
| Placebo | 6/168 (3.6%) | 58/168 (34.5%) | 56/168 (33.3%) |
| Event | Teze 420 mg Q4W | Placebo |
|---|---|---|
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 20/165 | 26/168 |
| PneumoniaInfections and infestations | 7/165 | 5/168 |
| Pneumonia bacterialInfections and infestations | 3/165 | 3/168 |
| COVID-19Infections and infestations | 2/165 | 3/168 |
| DiverticulitisInfections and infestations | 2/165 | 1/168 |
| Myocardial infarctionCardiac disorders | 2/165 | 0/168 |
| Transient ischaemic attackNervous system disorders | 2/165 | 0/168 |
| Benign prostatic hyperplasiaReproductive system and breast disorders | 2/165 | 0/168 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 2/165 | 1/168 |
| Inguinal herniaGastrointestinal disorders | 2/165 | 0/168 |
| Event | Teze 420 mg Q4W | Placebo |
|---|---|---|
| COVID-19Infections and infestations | 25/165 | 16/168 |
| NasopharyngitisInfections and infestations | 17/165 | 9/168 |
| HypertensionVascular disorders | 12/165 | 5/168 |
| Oedema peripheralGeneral disorders | 11/165 | 8/168 |
| FallInjury, poisoning and procedural complications | 11/165 | 10/168 |
| ContusionInjury, poisoning and procedural complications | 10/165 | 0/168 |
| Urinary tract infectionInfections and infestations | 5/165 | 10/168 |
| HeadacheNervous system disorders | 3/165 | 10/168 |
| DizzinessNervous system disorders | 9/165 | 1/168 |
| DiarrhoeaGastrointestinal disorders | 9/165 | 4/168 |
The Full Analysis Set included all participants randomised to study treatment who received at least one dose of investigational product, irrespective of their protocol adherence, and continued participation in the study.
| Age, Continuous(Years) | Tezepelumab | Placebo | Total |
|---|---|---|---|
| Age (Years) | 67.4 ± 6.75 | 67.1 ± 7.24 | 67.2 ± 7.00 |
| Age, Customized(Participants) | Tezepelumab | Placebo | Total |
|---|---|---|---|
| Age Group : >=40 - <65 | 52 | 61 | 113 |
| Age Group : >=65 - <=80 | 113 | 107 | 220 |
| Sex: Female, Male(Participants) | Tezepelumab | Placebo | Total |
|---|---|---|---|
| Sex — Female | 77 | 68 | 145 |
| Sex — Male | 88 | 100 | 188 |
| Ethnicity (NIH/OMB)(Participants) | Tezepelumab | Placebo | Total |
|---|---|---|---|
| Ethnic Group — Hispanic or Latino | 7 | 3 | 10 |
| Ethnic Group — Not Hispanic or Latino | 158 | 165 | 323 |
| Ethnic Group — Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Tezepelumab | Placebo | Total |
|---|---|---|---|
| Race — White | 147 | 146 | 293 |
| Race — Black or African American | 2 | 2 | 4 |
| Race — Asian | 16 | 18 | 34 |
| Race — Other | 0 | 2 | 2 |
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Pulmonary Disease, Chronic Obstructive→
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