Tezepelumab COPD Exacerbation study - COURSE

Study identifier:D5241C00001

ClinicalTrials.gov identifier:NCT04039113

EudraCT identifier:2019-001363-67

CTIS identifier:N/A

Study Complete

Official Title

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) (COURSE)

Medical condition

Chronic obstructive pulmonary disease (COPD)

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

337

Study type

Interventional

Age

40 Years - 80 Years

Date

Study Start Date: 30 Jul 2019

Primary Completion Date: 10 Nov 2023

Study Completion Date: 31 Jan 2024

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2025 by AstraZeneca

Collaborators

Amgen

Inclusion and exclusion criteria

Location

Research Site

Truro, NS, Canada, B2N 1L2

Location

Research Site

Montréal, QC, Canada, H1M 1B1

Location

Research Site

Quebec, QC, Canada, G3K 2P8

Location

Research Site

Burlington, ON, Canada, L7N 3V2

Location

Research Site

St Charles Borromee, QC, Canada, J6E 2B4

Location

Research Site

Calgary, AB, Canada, T2N 4Z6

Location

Research Site

Seoul, Republic of Korea, 06591

Location

Research Site

Jeonju-si, Republic of Korea, 54907

Arms	Assigned Interventions
Active Comparator: Tezepelumab Tezepelumab, SC, Q4W	Biological/Vaccine: Tezepelumab Tezepelumab subcutaneous injection Other Name: Tezepelumab
Placebo Comparator: Matching Placebo Matching placebo, SC, Q4W	Other: Placebo Placebo subcutaneous injection

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of a screening period for approximately 6 weeks. At the end of the screening period, participants were randomised in 1:1 ratio for tezepelumab or placebo. Randomisation was stratified by region (North America, Europe, Asia), and number of prior exacerbations (2, >=3) recorded at randomisation in IWRS.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Participant Flow: Overall Study

	Tezepelumab	Placebo
STARTED	169	168
Received Treatment	165	168
Completed Treatment	138	138
COMPLETED	146	150
NOT COMPLETED	23	18
Withdrawal by Subject	8	11
Lost to Follow-up	1	1
Adverse Event	2	2
Death	2	4
Site Closure	6	0
Failure to meet randomisation criteria	4	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

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.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Baseline Measures

	Tezepelumab	Placebo	Total
Number of Participants [units: Participants]	165	168	333
Age Continuous [units: Years] Mean ± Standard Deviation Age (Years)	67.4 ± 6.75	67.1 ± 7.24	67.2 ± 7.00
Age, Customized ^[1] [units: Participants]
Age Group : >=40 - <65	52	61	113
Age Group : >=65 - <=80	113	107	220
Sex: Female, Male [units: Participants] Sex
Female	77	68	145
Male	88	100	188
Race/Ethnicity, Customized ^[2] [units: Participants] Race
White	147	146	293
Black or African American	2	2	4
Asian	16	18	34
Other	0	2	2
Ethnicity (NIH/OMB) [units: Participants] Ethnic Group
Hispanic or Latino	7	3	10
Not Hispanic or Latino	158	165	323
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD. [ Time Frame: From randomisation up to Week 52 ]

Measure Type	Primary
Measure Name	Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD.
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD. [units: exacerbations per year] Least Squares Mean (90% Confidence Interval)	1.75 (1.45 to 2.11)	2.11 (1.77 to 2.53)

Statistical Analysis 1 for Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD.

Groups^[1]	All groups
Method^[3]	Other [Negative Binomial]
P-Value^[4]	0.1042
Other^[5]	0.83
90% Confidence Interval	( 0.64 to 1.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	1-sided p-value
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Rate of moderate or severe COPD exacerbations in participants with moderate to very severe COPD.

Groups^[1]	All groups
Method^[3]	Other [Negative Binomial]
P-Value^[4]	0.2085
Other^[5]	0.83
95% Confidence Interval	( 0.61 to 1.11 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	2-sided p-value
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Time to first moderate/severe COPD exacerbation [ Time Frame: From randomisation up to Week 52 ]

Measure Type	Secondary
Measure Name	Time to first moderate/severe COPD exacerbation
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Time to first moderate/severe COPD exacerbation [units: Participants]	94	105

No statistical analysis provided for Time to first moderate/severe COPD exacerbation

3. Secondary Outcome Measure: Proportion of participants COPD exacerbation free at Week 52 [ Time Frame: From randomisation up to Week 52 ]

Measure Type	Secondary
Measure Name	Proportion of participants COPD exacerbation free at Week 52
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Proportion of participants COPD exacerbation free at Week 52 [units: participants]	71	63

No statistical analysis provided for Proportion of participants COPD exacerbation free at Week 52

4. Secondary Outcome Measure: Comparison of annual severe COPD exacerbation rates over 52 weeks [ Time Frame: From randomisation up to Week 52 ]

Measure Type	Secondary
Measure Name	Comparison of annual severe COPD exacerbation rates over 52 weeks
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Comparison of annual severe COPD exacerbation rates over 52 weeks [units: exacerbations per year] Least Squares Mean (90% Confidence Interval)	0.13 (0.07 to 0.24)	0.25 (0.15 to 0.42)

No statistical analysis provided for Comparison of annual severe COPD exacerbation rates over 52 weeks

5. Secondary Outcome Measure: Proportion of participants with >=1 severe COPD exacerbations over 52 weeks [ Time Frame: From randomisation up to Week 52 ]

Measure Type	Secondary
Measure Name	Proportion of participants with >=1 severe COPD exacerbations over 52 weeks
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Proportion of participants with >=1 severe COPD exacerbations over 52 weeks [units: participants]	16	22

No statistical analysis provided for Proportion of participants with >=1 severe COPD exacerbations over 52 weeks

6. Secondary Outcome Measure: Time to first severe COPD exacerbation [ Time Frame: From randomisation up to Week 52 ]

Measure Type	Secondary
Measure Name	Time to first severe COPD exacerbation
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Time to first severe COPD exacerbation [units: Participants]	16	22

No statistical analysis provided for Time to first severe COPD exacerbation

7. Secondary Outcome Measure: Least square (LS) mean difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 (FEV1) at Week 52 [ Time Frame: Baseline and Week 52 ]

Measure Type	Secondary
Measure Name	Least square (LS) mean difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 (FEV1) at Week 52
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants analyzed is the number of participants with an observation at Week 52. All participants from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	163	166
Least square (LS) mean difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 (FEV1) at Week 52 [units: Liters] Least Squares Mean (Standard Error)	0.026 (0.015)	-0.029 (0.015)

No statistical analysis provided for Least square (LS) mean difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 (FEV1) at Week 52

8. Secondary Outcome Measure: Lease square (LS) mean difference in change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52 [ Time Frame: Baseline and Week 52 ]

Measure Type	Secondary
Measure Name	Lease square (LS) mean difference in change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants analyzed is the number of participants with an observation at Week 52. All participants from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	157	156
Lease square (LS) mean difference in change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52 [units: units on a scale] Least Squares Mean (Standard Error)	-4.796 (1.176)	-1.863 (1.189)

No statistical analysis provided for Lease square (LS) mean difference in change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52

9. Secondary Outcome Measure: 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 [ Time Frame: Baseline and Week 52 ]

Measure Type	Secondary
Measure Name	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
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants analyzed is the number of participants from the Full Analysis Set with a baseline SGRQ score.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	163	163
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 [units: participants]	65	59

No statistical analysis provided for 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

10. Secondary Outcome Measure: Least square (LS) mean difference in change from baseline in COPD assessment tool (CAT) total score at Week 52 [ Time Frame: Baseline and Week 52 ]

Measure Type	Secondary
Measure Name	Least square (LS) mean difference in change from baseline in COPD assessment tool (CAT) total score at Week 52
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants analyzed is the number of participants with an observation at Week 52. All participants from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	159	162
Least square (LS) mean difference in change from baseline in COPD assessment tool (CAT) total score at Week 52 [units: units on a scale] Least Squares Mean (Standard Error)	-3.037 (0.524)	-1.182 (0.524)

No statistical analysis provided for Least square (LS) mean difference in change from baseline in COPD assessment tool (CAT) total score at Week 52

11. Secondary Outcome Measure: Serum concentration of Tezepelumab [ Time Frame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled ]

Measure Type	Secondary
Measure Name	Serum concentration of Tezepelumab
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic (PK) analysis set comprises all subjects who received at least one dose of tezepelumab and have at least one detectable serum concentration post first dose that is not affected by factors such as protocol deviations (e.g. disallowed medication or incorrect study medication received).

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	162	0
Serum concentration of Tezepelumab [units: microgram per milliliter (mg/mL)] Mean (Standard Deviation)
Week 0	NA (NA)^[1]
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)

No statistical analysis provided for Serum concentration of Tezepelumab

12. Secondary Outcome Measure: Number of participants with Anti-Drug Antibody (ADA) response to Tezepelumab [ Time Frame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled ]

Measure Type	Secondary
Measure Name	Number of participants with Anti-Drug Antibody (ADA) response to Tezepelumab
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set included all subjects who received at least one dose of study drug.

Reporting Groups

	Description
Tezepelumab	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Measured Values

	Tezepelumab	Placebo
Number of Participants Analyzed [units:participants]	165	168
Number of participants with Anti-Drug Antibody (ADA) response to Tezepelumab [units: Participants]
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

No statistical analysis provided for Number of participants with Anti-Drug Antibody (ADA) response to Tezepelumab

Serious Adverse Events

Time Frame	From first dose of study drug until end of study at Week 64.
Additional Description	All AE data is based off the Safety Analysis Set, which includes all subjects who received at least one dose of study treatment.

Reporting Groups

	Description
Teze 420 mg Q4W	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Serious Adverse Events

Teze 420 mg Q4W

Placebo

Total, serious adverse events

# participants affected / at risk

56/165 (33.94%)

58/168 (34.52%)

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

General disorders and administration site conditions

Vascular stent stenosis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Hepatobiliary disorders

Cholangitis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Hepatobiliary disorders

Cholecystitis¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Hepatobiliary disorders

Cholecystitis acute¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

1/165 (0.61%)

1/168 (0.60%)

# events

Hepatobiliary disorders

Hepatitis alcoholic¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Immune system disorders

Drug hypersensitivity¹,^†

# participants affected / at risk

1/165 (0.61%)

1/168 (0.60%)

# events

Infections and infestations

Appendicitis¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

2/165 (1.21%)

3/168 (1.79%)

# events

Infections and infestations

COVID-19 pneumonia¹,^†

# participants affected / at risk

1/165 (0.61%)

1/168 (0.60%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

2/165 (1.21%)

1/168 (0.60%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

1/165 (0.61%)

1/168 (0.60%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection bacterial¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Meningitis viral¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Cardiac disorders

Atrioventricular block complete¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

7/165 (4.24%)

5/168 (2.98%)

# events

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

3/165 (1.82%)

3/168 (1.79%)

# events

Infections and infestations

Pneumonia klebsiella¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Infections and infestations

Pneumonia mycoplasmal¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Pneumonia pneumococcal¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Pneumonia pseudomonal¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Infections and infestations

Pneumonia viral¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Infections and infestations

Post procedural infection¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Pseudomonas bronchitis¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Cardiac disorders

Cardiac disorder¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Injury, poisoning and procedural complications

Cervical vertebral fracture¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Injury, poisoning and procedural complications

Femoral neck fracture¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Injury, poisoning and procedural complications

Gun shot wound¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Injury, poisoning and procedural complications

Limb traumatic amputation¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Injury, poisoning and procedural complications

Pelvic fracture¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Injury, poisoning and procedural complications

Procedural dizziness¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Injury, poisoning and procedural complications

Procedural pneumothorax¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Injury, poisoning and procedural complications

Road traffic accident¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Injury, poisoning and procedural complications

Spinal fracture¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Cardiac disorders

Left ventricular failure¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

2/165 (1.21%)

0/168 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma pancreas¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder transitional cell carcinoma¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal melanoma¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma stage I¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma stage II¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage I¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm malignant¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal adenocarcinoma stage IV¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal squamous cell carcinoma stage IV¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer metastatic¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uterine cancer¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Cardiac disorders

Supraventricular extrasystoles¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Nervous system disorders

Ischaemic cerebral infarction¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Nervous system disorders

Subarachnoid haemorrhage¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Nervous system disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

2/165 (1.21%)

0/168 (0.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/165 (0.61%)

1/168 (0.60%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Renal and urinary disorders

Renal artery occlusion¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Reproductive system and breast disorders

Benign prostatic hyperplasia¹,^†

# participants affected / at risk

2/165 (1.21%)

0/168 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

2/165 (1.21%)

1/168 (0.60%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

20/165 (12.12%)

26/168 (15.48%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax spontaneous¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary artery thrombosis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Blood and lymphatic system disorders

Blood loss anaemia¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Vascular disorders

Aortic aneurysm¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Vascular disorders

Coeliac artery occlusion¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Vascular disorders

Iliac artery dissection¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Vascular disorders

Peripheral artery occlusion¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Vascular disorders

Peripheral artery thrombosis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Gastrointestinal disorders

Alcoholic pancreatitis¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Blood and lymphatic system disorders

Lymphadenopathy¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Gastrointestinal disorders

Haemorrhoids¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Gastrointestinal disorders

Inguinal hernia¹,^†

# participants affected / at risk

2/165 (1.21%)

0/168 (0.00%)

# events

Gastrointestinal disorders

Intestinal ischaemia¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Gastrointestinal disorders

Mechanical ileus¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Gastrointestinal disorders

Obstructive pancreatitis¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Gastrointestinal disorders

Oesophageal ulcer¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Gastrointestinal disorders

Retroperitoneal haemorrhage¹,^†

# participants affected / at risk

1/165 (0.61%)

0/168 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/165 (0.00%)

1/168 (0.60%)

# events

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

2/165 (1.21%)

1/168 (0.60%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.1

Other Adverse Events

Time Frame	From first dose of study drug until end of study at Week 64.
Additional Description	All AE data is based off the Safety Analysis Set, which includes all subjects who received at least one dose of study treatment.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Teze 420 mg Q4W	420 mg Tezepelumab injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).
Placebo	Matching Placebo injection delivered subcutaneously every 4 weeks up to maximum of 52 weeks (last dose given at week 48).

Other Adverse Events

Teze 420 mg Q4W

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

78/165 (47.27%)

56/168 (33.33%)

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

11/165 (6.67%)

8/168 (4.76%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

25/165 (15.15%)

16/168 (9.52%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

17/165 (10.30%)

9/168 (5.36%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

5/165 (3.03%)

10/168 (5.95%)

# events

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

10/165 (6.06%)

0/168 (0.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

11/165 (6.67%)

10/168 (5.95%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

9/165 (5.45%)

1/168 (0.60%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/165 (1.82%)

10/168 (5.95%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

12/165 (7.27%)

5/168 (2.98%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

9/165 (5.45%)

4/168 (2.38%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The Investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect proprietary information and to provide comments.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Dave Singh

Division of Infection, Immunity & Resp Medicine, The University of Manchester, United Kingdom

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR Synopsis

Trial Results Summaries