Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of MEDI3506 in Adults With Uncontrolled Moderate-to-severe Asthma (NCT NCT04570657)
NCT ID: NCT04570657
Last Updated: 2024-01-30
Results Overview
In-clinic spirometry measurements were taken prior to the administration of bronchodilators. Baseline was the last measurement prior to first injection of investigational product (IP). The least squares (LS) means, LS mean differences and 80% confidence intervals (CIs), and one-sided p-value results were based on a mixed model repeated measures (MMRM). The model included fixed effects for baseline, background medication, geographic region, baseline inhaled corticosteroids (ICS) total daily dose, visit, treatment, and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements.
COMPLETED
PHASE2
250 participants
Baseline and week 16
2024-01-30
Participant Flow
Participants were enrolled and randomised in 52 study centres in 7 countries including Argentina, Germany, Hungary, Poland, South Africa, the United Kingdom, and the United States from 17 September 2020. The last participant completed their last study visit on 06 February 2023.
Adult participants with uncontrolled moderate to severe asthma were randomised in a 1:1:1 ratio to receive tozorakimab (MEDI3506) Dose A (lower dose), tozorakimab Dose B (higher dose), or placebo. Of the 478 participants screened, 250 were enrolled, and of these, 15 were excluded from analysis due to invalidity of data (see limitations and caveats for further details).
Participant milestones
| Measure |
Tozorakimab Dose A
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Overall Study
STARTED
|
77
|
77
|
81
|
|
Overall Study
Intent to Treat (ITT) Population
|
77
|
77
|
81
|
|
Overall Study
As-treated Population
|
77
|
77
|
81
|
|
Overall Study
Pharmacokinetic (PK) Population
|
75
|
77
|
0
|
|
Overall Study
COMPLETED
|
76
|
74
|
77
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
4
|
Reasons for withdrawal
| Measure |
Tozorakimab Dose A
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
2
|
Baseline Characteristics
Study to Assess the Efficacy and Safety of MEDI3506 in Adults With Uncontrolled Moderate-to-severe Asthma
Baseline characteristics by cohort
| Measure |
Tozorakimab Dose A
n=77 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
Total
n=235 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
26 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
83 Participants
n=4 Participants
|
|
Age, Continuous
|
42.1 years
STANDARD_DEVIATION 11.97 • n=5 Participants
|
43.1 years
STANDARD_DEVIATION 12.37 • n=7 Participants
|
48.3 years
STANDARD_DEVIATION 10.41 • n=5 Participants
|
44.5 years
STANDARD_DEVIATION 11.87 • n=4 Participants
|
|
Sex: Female, Male
Female
|
53 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
150 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
51 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
152 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
71 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
210 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
In-clinic spirometry measurements were taken prior to the administration of bronchodilators. Baseline was the last measurement prior to first injection of investigational product (IP). The least squares (LS) means, LS mean differences and 80% confidence intervals (CIs), and one-sided p-value results were based on a mixed model repeated measures (MMRM). The model included fixed effects for baseline, background medication, geographic region, baseline inhaled corticosteroids (ICS) total daily dose, visit, treatment, and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements.
Outcome measures
| Measure |
Tozorakimab Dose A
n=76 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Change From Baseline to Week 16 in Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in the First Second (FEV1) as Measured in the Study Clinic
|
0.148 litres
Standard Error 0.047
|
0.116 litres
Standard Error 0.048
|
0.112 litres
Standard Error 0.046
|
SECONDARY outcome
Timeframe: Baseline and weeks 8 and 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
In-clinic spirometry measurements were taken following the use of bronchodilators. Bronchodilatation was induced using albuterol (90 µg metered dose), salbutamol (100 µg metered dose), or levalbuterol (45 µg metered dose), and measurements were taken after up to a maximum of 4 inhalations. Baseline was the last measurement prior to first injection of IP. The LS means, LS mean differences and 80% CIs, and one-sided p-value results were based on MMRM. The model included fixed effects for baseline, background medication, geographic region, baseline ICS total daily dose, visit, treatment, and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements.
Outcome measures
| Measure |
Tozorakimab Dose A
n=24 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=25 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=35 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Change From Baseline to Weeks 8 and 16 in Post-bronchodilator (Post-BD) FEV1 as Measured in the Study Clinic
Week 8
|
-0.062 litres
Standard Error 0.067
|
0.008 litres
Standard Error 0.068
|
-0.050 litres
Standard Error 0.060
|
|
Change From Baseline to Weeks 8 and 16 in Post-bronchodilator (Post-BD) FEV1 as Measured in the Study Clinic
Week 16
|
-0.064 litres
Standard Error 0.067
|
-0.050 litres
Standard Error 0.068
|
-0.026 litres
Standard Error 0.060
|
SECONDARY outcome
Timeframe: Pharmacokinetic (PK) samples were taken pre-dose (day 1) and at weeks 1, 4, 8, 12, 16, 20, and 24Population: The PK population included participants who received at least one dose of tozorakimab and had at least one detectable serum concentration measurement post-first dose of study intervention. Participants with data available at each time point are presented.
Tozorakimab serum concentrations were measured using a validated assay method.
Outcome measures
| Measure |
Tozorakimab Dose A
n=75 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Serum Concentrations of Tozorakimab
Pre-dose
|
NA µg/L
Geometric Coefficient of Variation NA
Geometric mean (CV%) could not be calculated due to too many samples with tozorakimab concentrations below the limit of quantification.
|
NA µg/L
Geometric Coefficient of Variation NA
Geometric mean (CV%) could not be calculated due to too many samples with tozorakimab concentrations below the limit of quantification.
|
—
|
|
Serum Concentrations of Tozorakimab
Week 1
|
8939.24 µg/L
Geometric Coefficient of Variation 367.31
|
18374.15 µg/L
Geometric Coefficient of Variation 239.89
|
—
|
|
Serum Concentrations of Tozorakimab
Week 4
|
2165.82 µg/L
Geometric Coefficient of Variation 180.17
|
4102.04 µg/L
Geometric Coefficient of Variation 168.60
|
—
|
|
Serum Concentrations of Tozorakimab
Week 8
|
2680.07 µg/L
Geometric Coefficient of Variation 113.59
|
4476.11 µg/L
Geometric Coefficient of Variation 109.27
|
—
|
|
Serum Concentrations of Tozorakimab
Week 12
|
2673.94 µg/L
Geometric Coefficient of Variation 121.08
|
4646.57 µg/L
Geometric Coefficient of Variation 153.62
|
—
|
|
Serum Concentrations of Tozorakimab
Week 16
|
2742.93 µg/L
Geometric Coefficient of Variation 128.83
|
5007.93 µg/L
Geometric Coefficient of Variation 117.76
|
—
|
|
Serum Concentrations of Tozorakimab
Week 20
|
356.56 µg/L
Geometric Coefficient of Variation 177.25
|
761.75 µg/L
Geometric Coefficient of Variation 152.78
|
—
|
|
Serum Concentrations of Tozorakimab
Week 24
|
80.36 µg/L
Geometric Coefficient of Variation 170.34
|
146.67 µg/L
Geometric Coefficient of Variation 214.16
|
—
|
SECONDARY outcome
Timeframe: Blood samples were taken pre-dose (day 1) and at weeks 1, 4, 8, 12, 16, and 24Population: The as-treated population included participants who were randomised and received any study intervention. Participants with data available are included.
ADA prevalence is the number of participants ADA positive (ADA+) at baseline and/or post-baseline. Treatment-emergent ADA+ (TE-ADA +) positive is defined as being either of treatment-induced ADA+ (ADA negative \[ADA-\] at baseline and at least one post-baseline ADA+) and treatment-boosted ADA+ (ADA+ at baseline and baseline titre is boosted by ≥ 4-fold increase at ≥ 1 post-baseline time point). Treatment-emergent ADA- (TE-ADA-) is defined as ADA+ but not fulfilling the definition of TE-ADA+. ADA persistently positive is defined as ADA- at baseline and ADA+ at ≥ 2 post-baseline assessment with ≥ 16 weeks between first and last positive assessments, or ADA+ at the last post-baseline assessment. ADA transiently positive is defined as ADA- at baseline, having at least one post-baseline ADA+ assessment and not fulfilling the conditions of ADA persistently positive. Baseline is defined as the last ADA assessment prior to first injection of IP.
Outcome measures
| Measure |
Tozorakimab Dose A
n=77 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Number of Participants With Anti-drug Antibodies (ADAs)
ADA prevalence
|
3 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Anti-drug Antibodies (ADAs)
TE-ADA+
|
3 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Anti-drug Antibodies (ADAs)
Treatment-induced ADA+
|
3 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Anti-drug Antibodies (ADAs)
TE-ADA-
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Anti-drug Antibodies (ADAs)
Both baseline and post-baseline positive
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Anti-drug Antibodies (ADAs)
ADA persistently positive
|
3 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Anti-drug Antibodies (ADAs)
ADA transiently positive
|
0 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
In the ACQ-6, participants were asked to recall how their asthma has been during the previous week by responding to one BD-use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between \>0.75 and \<1.5 indicate partly controlled asthma, and scores ≥1.5 indicate not well-controlled asthma. Results were based on an MMRM which included fixed effects for baseline, background medication, geographic region, baseline ICS total daily dose, visit, treatment and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements. A negative change from baseline indicates an improvement in asthma control.
Outcome measures
| Measure |
Tozorakimab Dose A
n=76 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Change From Baseline to Week 16 in the Asthma Control Questionnaire-6 (ACQ-6) Score
|
-0.925 score on a scale
Standard Error 0.117
|
-0.942 score on a scale
Standard Error 0.117
|
-0.895 score on a scale
Standard Error 0.112
|
SECONDARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with evaluable ACQ-6 scores were included in the analysis.
In the ACQ-6, participants were asked to recall how their asthma has been during the previous week by responding to one BD-use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between \>0.75 and \<1.5 indicate partly controlled asthma, and scores ≥1.5 indicate not well-controlled asthma. A decrease in ACQ-6 score baseline indicates an improvement in asthma control, and individual changes of at least 0.5 are considered clinically meaningful.
Outcome measures
| Measure |
Tozorakimab Dose A
n=73 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=74 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=77 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Number of Participants With a Decrease in ACQ-6 Score ≥ 0.5 From Baseline to Week 16
|
53 Participants
|
56 Participants
|
53 Participants
|
SECONDARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with evaluable ACQ-6 scores were included in the analysis.
In the ACQ-6, participants were asked to recall how their asthma has been during the previous week by responding to one BD-use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between \>0.75 and \<1.5 indicate partly controlled asthma, and scores ≥1.5 indicate not well-controlled asthma.
Outcome measures
| Measure |
Tozorakimab Dose A
n=73 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=74 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=77 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Number of Participants Achieving ACQ-6 Well Controlled Status at Week 16
|
17 Participants
|
18 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
The SGRQ is a 50-item patient-reported outcome instrument to measure the health status of participants with airway obstruction diseases, giving a total score and 3 domain scores (symptoms, activity, and impacts). The total score is expressed as a percentage of overall impairment, with 100 representing the worst possible health status and 0 the best possible health status. Each domain score ranges from 0 to 100, with higher scores indicating greater impairment. A negative change from baseline indicates an improvement in impairments. Results were based on an MMRM which included fixed effects for baseline, background medication, geographic region, baseline ICS total daily dose, visit, treatment and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements.
Outcome measures
| Measure |
Tozorakimab Dose A
n=76 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=80 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Change From Baseline to Week 16 in St George's Respiratory Questionnaire (SGRQ) Domain and Total Scores
SGRQ Activity Total Score
|
-10.340 score on a scale
Standard Error 2.477
|
-11.706 score on a scale
Standard Error 2.507
|
-10.342 score on a scale
Standard Error 2.390
|
|
Change From Baseline to Week 16 in St George's Respiratory Questionnaire (SGRQ) Domain and Total Scores
SGRQ Impacts Total Score
|
-8.237 score on a scale
Standard Error 1.750
|
-8.509 score on a scale
Standard Error 1.774
|
-6.816 score on a scale
Standard Error 1.689
|
|
Change From Baseline to Week 16 in St George's Respiratory Questionnaire (SGRQ) Domain and Total Scores
SGRQ Symptoms Total Score
|
-15.290 score on a scale
Standard Error 2.828
|
-19.130 score on a scale
Standard Error 2.873
|
-15.981 score on a scale
Standard Error 2.726
|
|
Change From Baseline to Week 16 in St George's Respiratory Questionnaire (SGRQ) Domain and Total Scores
SGRQ Total Score
|
-10.133 score on a scale
Standard Error 1.815
|
-11.366 score on a scale
Standard Error 1.838
|
-9.470 score on a scale
Standard Error 1.750
|
SECONDARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with evaluable SGRQ scores were included in the analysis.
The SGRQ is a 50-item patient-reported outcome instrument to measure the health status of participants with airway obstruction diseases, giving a total score and 3 domain scores (symptoms, activity, and impacts). The total score is expressed as a percentage of overall impairment, with 100 representing the worst possible health status and 0 the best possible health status. A decrease in the SGRQ total score indicates an improvement in overall impairment.
Outcome measures
| Measure |
Tozorakimab Dose A
n=73 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=74 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=77 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Number of Participants With a Decrease in SGRQ Total Score of ≥ 4 Points From Baseline to Week 16
|
50 Participants
|
53 Participants
|
54 Participants
|
SECONDARY outcome
Timeframe: Baseline to week 16Population: The ITT population included participant who were randomised and received any study intervention.
Asthma CompEx is a combination of exacerbations of asthma and diary events (i.e., a combination of electronic diary \[eDiary\] variables). eDiary events are defined by criteria using morning/evening diary variables of PEF, symptoms, and use of rescue medication. A participant was considered to have a CompEx event if they had one or both of an asthma exacerbation or diary event. For participants who did not experience an on-treatment CompEx event, date of censoring was the minimum between the date of last dose + 28 days, and the last day of eDiary recording during the on-treatment period.
Outcome measures
| Measure |
Tozorakimab Dose A
n=77 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Number of Participants With at Least One Asthma CompEx Event From Baseline to Week 16
|
19 Participants
|
15 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Baseline to week 16Population: The ITT population included participants who were randomised and received any study intervention.
The annualised rate of asthma CompEx events was calculated as the total number of asthma CompEx events / (date of last dose of IP + 28 - date of first dose of IP - recovery time + 1) / 365.25. The rates, rate ratios, and one-sided p-values were estimated from a negative binomial regression, with the log(follow up time) included as an offset term. The dependent variable will be the number of CompEx events during the on-treatment period (i.e., from baseline to last dose date +28 days), and the model will include treatment group, background medication, geographic region and baseline ICS total daily dose as covariates.
Outcome measures
| Measure |
Tozorakimab Dose A
n=77 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Asthma CompEx Annualised Event Rate
|
0.86 events per participant-treatment year
Interval 0.58 to 1.28
|
0.69 events per participant-treatment year
Interval 0.44 to 1.07
|
0.99 events per participant-treatment year
Interval 0.68 to 1.44
|
SECONDARY outcome
Timeframe: Baseline and week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
A standardised single-breath FeNO test was performed to evaluate airway inflammation. Results were based on MMRM on log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model were then back transformed. The model included fixed effects for baseline (in log), background medication, geographic region, baseline ICS total daily dose, visit, treatment and the baseline by visit and treatment by visit interactions. Visits within subject were considered as repeated measurements.
Outcome measures
| Measure |
Tozorakimab Dose A
n=74 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 16 in Concentration of Fractional Exhaled Nitric Oxide (FeNO) in Exhaled Breath
|
-17.429 percent change
Interval -23.423 to -10.965
|
-16.500 percent change
Interval -22.548 to -9.981
|
-5.007 percent change
Interval -11.612 to 2.091
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and week 16Population: Participants in the ITT population with 1 or ≥ 2 exacerbations in the previous 12 months are included in the analysis. The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
In-clinic spirometry measurements were taken prior to the administration of bronchodilators. Baseline was the last measurement prior to first injection of IP. The LS means, LS mean differences and 80% CIs, and one-sided p-value results were based on MMRM. The model included fixed effects for baseline, visit, treatment, and the baseline by visit and treatment by visit interactions. Visits within participant were considered as repeated measurements. Analysis is presented by the number of asthma exacerbations experienced within the 12 months prior to baseline (1 or ≥ 2 exacerbations in the previous 12 months).
Outcome measures
| Measure |
Tozorakimab Dose A
n=45 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=47 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=52 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Change From Baseline to Week 16 in Pre-BD FEV1 as Measured in the Study Clinic: Analysis Per Number of Exacerbations in Last 12 Months
1 Exacerbation in Last 12 Months
|
0.188 litres
Standard Error 0.065
|
0.042 litres
Standard Error 0.070
|
0.165 litres
Standard Error 0.062
|
|
Change From Baseline to Week 16 in Pre-BD FEV1 as Measured in the Study Clinic: Analysis Per Number of Exacerbations in Last 12 Months
≥ 2 Exacerbations in Last 12 Months
|
0.059 litres
Standard Error 0.067
|
0.194 litres
Standard Error 0.065
|
-0.018 litres
Standard Error 0.069
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Week 16Population: The ITT population included participants who were randomised and received any study intervention. Participants with data available are included.
The eosinophil count at baseline and week 16 are presented. Baseline was defined as the last measurement prior to first injection of IP.
Outcome measures
| Measure |
Tozorakimab Dose A
n=77 Participants
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 Participants
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 Participants
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Eosinophil Count
Baseline
|
0.187 10^9 cells/L
Geometric Coefficient of Variation 80.4
|
0.200 10^9 cells/L
Geometric Coefficient of Variation 88.4
|
0.178 10^9 cells/L
Geometric Coefficient of Variation 83.3
|
|
Eosinophil Count
Week 16
|
0.122 10^9 cells/L
Geometric Coefficient of Variation 82.9
|
0.136 10^9 cells/L
Geometric Coefficient of Variation 77.6
|
0.185 10^9 cells/L
Geometric Coefficient of Variation 93.2
|
Adverse Events
Tozorakimab Dose A
Tozorakimab Dose B
Placebo
Serious adverse events
| Measure |
Tozorakimab Dose A
n=77 participants at risk
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 participants at risk
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 participants at risk
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
1.3%
1/77 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/81 • Day 1 to Week 24 (up to 24 weeks)
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
1.2%
1/81 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
2.6%
2/77 • Number of events 2 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/81 • Day 1 to Week 24 (up to 24 weeks)
|
|
Gastrointestinal disorders
Acid peptic disease
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
1.3%
1/77 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/81 • Day 1 to Week 24 (up to 24 weeks)
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
1.2%
1/81 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
|
General disorders
Asthenia
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
1.3%
1/77 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/81 • Day 1 to Week 24 (up to 24 weeks)
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
1.3%
1/77 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/81 • Day 1 to Week 24 (up to 24 weeks)
|
Other adverse events
| Measure |
Tozorakimab Dose A
n=77 participants at risk
Participants were randomised to receive tozorakimab Dose A by subcutaneous (SC) injection.
|
Tozorakimab Dose B
n=77 participants at risk
Participants were randomised to receive tozorakimab Dose B by SC injection.
|
Placebo
n=81 participants at risk
Participants were randomised to receive placebo by SC injection.
|
|---|---|---|---|
|
Infections and infestations
COVID-19
|
19.5%
15/77 • Number of events 17 • Day 1 to Week 24 (up to 24 weeks)
|
13.0%
10/77 • Number of events 12 • Day 1 to Week 24 (up to 24 weeks)
|
13.6%
11/81 • Number of events 12 • Day 1 to Week 24 (up to 24 weeks)
|
|
Infections and infestations
Nasopharyngitis
|
7.8%
6/77 • Number of events 6 • Day 1 to Week 24 (up to 24 weeks)
|
6.5%
5/77 • Number of events 6 • Day 1 to Week 24 (up to 24 weeks)
|
4.9%
4/81 • Number of events 5 • Day 1 to Week 24 (up to 24 weeks)
|
|
General disorders
Injection site erythema
|
5.2%
4/77 • Number of events 5 • Day 1 to Week 24 (up to 24 weeks)
|
9.1%
7/77 • Number of events 15 • Day 1 to Week 24 (up to 24 weeks)
|
2.5%
2/81 • Number of events 5 • Day 1 to Week 24 (up to 24 weeks)
|
|
Infections and infestations
Urinary tract infection
|
5.2%
4/77 • Number of events 4 • Day 1 to Week 24 (up to 24 weeks)
|
2.6%
2/77 • Number of events 2 • Day 1 to Week 24 (up to 24 weeks)
|
3.7%
3/81 • Number of events 3 • Day 1 to Week 24 (up to 24 weeks)
|
|
General disorders
Injection site swelling
|
0.00%
0/77 • Day 1 to Week 24 (up to 24 weeks)
|
5.2%
4/77 • Number of events 5 • Day 1 to Week 24 (up to 24 weeks)
|
1.2%
1/81 • Number of events 4 • Day 1 to Week 24 (up to 24 weeks)
|
|
General disorders
Injection site urticaria
|
1.3%
1/77 • Number of events 1 • Day 1 to Week 24 (up to 24 weeks)
|
5.2%
4/77 • Number of events 7 • Day 1 to Week 24 (up to 24 weeks)
|
0.00%
0/81 • Day 1 to Week 24 (up to 24 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place