Study to evaluate efficacy & safety of tralokinumab in subjects with asthma inadequately controlled on corticosteroids - MESOS

Study identifier:D2210C00014

ClinicalTrials.gov identifier:NCT02449473

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicentre, Randomized, Double-blind, Parallel Group, Placebo Controlled, 12-Week, Ph 2 Study to Evaluate the Effect of Tralokinumab on Airway Inflammation in Adults with Asthma Inadequately Controlled on Inhaled Corticosteroid (MESOS)

Medical condition

asthma

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 29 Sept 2015

Primary Completion Date: 21 Jun 2017

Study Completion Date: 21 Jun 2017

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2019 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Vancouver, BC, Canada, V5Z 1M9

Location

Research Site

Montreal, QC, Canada, H4A 3J1

Location

Research Site

Quebec, QC, Canada, G1V 4G5

Location

Research Site

Leicester, United Kingdom, LE3 9QP

Location

Research Site

Nottingham, United Kingdom, NG5 1PB

Location

Research Site

Manchester, United Kingdom, M23 9QZ

Location

Research Site

Glasgow, United Kingdom, G12 OYN

Location

Research Site

London, United Kingdom

Arms	Assigned Interventions
Experimental: Tralokinumab Dose Regimen Tralokinumab Subcutaneous Injection	Biological/Vaccine: Tralokinumab Subcutaneous Injection
Placebo Comparator: Placebo Dose Regimen Placebo Subcutaneous Injection	Other: 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
First patient enrolled: 29 Sep 2015; Last patient last visit: 21 Jun 2017. Study performed at 14 sites in 3 countries. Patients maintained on currently prescribed inhaled corticosteroid (≥250 micrograms fluticasone dry powder formulation equivalents total daily dose) + any additional maintenance asthma controller medication throughout the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
79 patients were randomised to receive investigational product (IP) and all those randomised received treatment.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 milligrams (mg) administered subcutaneously every 2 weeks (Q2W) over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Participant Flow: Overall Study

	Tralo 300 mg Q2W	Placebo
STARTED	39	40
COMPLETED	39	40
NOT COMPLETED	0	0

Baseline Characteristics

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

All patients in the full analysis set (FAS) and who received any IP (tralokinumab or placebo) were included in the baseline analysis.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Baseline Measures

	Tralo 300 mg Q2W	Placebo	Total
Number of Participants [units: Participants]	39	40	79
Age Continuous [units: Years] Mean ± Standard Deviation	47.1 ± 14.2	50.1 ± 14.2	48.6 ± 14.2
Sex: Female, Male [units: Participants]
Female	23	20	43
Male	16	20	36
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0
Asian	3	0	3
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	2	1	3
White	34	39	73
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Change from baseline to Week 12, expressed as a ratio, in number of airway submucosal eosinophils [ Time Frame: Baseline (Week 0) and Week 12 ]

Measure Type	Primary
Measure Name	Change from baseline to Week 12, expressed as a ratio, in number of airway submucosal eosinophils
Measure Description	The number of airway submucosal eosinophils per millimetre squared (mm^2) was determined by microscopic evaluation of bronchoscopic biopsies. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of airway submucosal eosinophils is presented as geometric mean ± standard deviation (SD) of log values.
Time Frame	Baseline (Week 0) and Week 12
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 FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Measured Values

	Tralo 300 mg Q2W	Placebo
Number of Participants Analyzed [units:participants]	35	39
Change from baseline to Week 12, expressed as a ratio, in number of airway submucosal eosinophils [units: Ratio] Geometric Mean (Standard Deviation)	1.29 (2.06)	1.07 (1.87)

Statistical Analysis 1 for Change from baseline to Week 12, expressed as a ratio, in number of airway submucosal eosinophils

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.3862
Other^[5]	1.43
95% Confidence Interval	( 0.63 to 3.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of change from baseline, expressed as a ratio, in airway submucosal eosinophils; Tralo 300 mg Q2W vs placebo. The null hypothesis was that the change in airway submucosal eosinophils at Week 12 on tralokinumab was equal to the corresponding change on placebo.
[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:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Change from baseline to Week 12, expressed as a ratio, in number of blood eosinophils [ Time Frame: Baseline (Week 0) and Week 12 ]

Measure Type	Secondary
Measure Name	Change from baseline to Week 12, expressed as a ratio, in number of blood eosinophils
Measure Description	The blood eosinophil count was obtained from the total and differential white blood cell counts. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of blood eosinophils is presented as geometric mean ± SD of log values.
Time Frame	Baseline (Week 0) and Week 12
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 FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Measured Values

	Tralo 300 mg Q2W	Placebo
Number of Participants Analyzed [units:participants]	33	37
Change from baseline to Week 12, expressed as a ratio, in number of blood eosinophils [units: Ratio] Geometric Mean (Standard Deviation)	1.10 (0.38)	0.91 (0.46)

Statistical Analysis 1 for Change from baseline to Week 12, expressed as a ratio, in number of blood eosinophils

Groups^[1]	All groups
Method^[3]	Other [Repeated measures analysis]
P-Value^[4]	0.0546
Other^[5]	1.21
95% Confidence Interval	( 1.00 to 1.48 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of change from baseline, expressed as a ratio, in blood eosinophil count; Tralo 300 mg Q2W vs placebo.
[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:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Change from baseline to Week 12, expressed as a ratio, in number of differential sputum eosinophils [ Time Frame: Baseline (Week 0) and Week 12 ]

Measure Type	Secondary
Measure Name	Change from baseline to Week 12, expressed as a ratio, in number of differential sputum eosinophils
Measure Description	Sputum induction was performed to obtain satisfactory samples of sputum originating from the airways. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of eosinophils in induced sputum is presented as geometric mean ± SD of log values.
Time Frame	Baseline (Week 0) and Week 12
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 FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Measured Values

	Tralo 300 mg Q2W	Placebo
Number of Participants Analyzed [units:participants]	16	17
Change from baseline to Week 12, expressed as a ratio, in number of differential sputum eosinophils [units: Ratio] Geometric Mean (Standard Deviation)	0.20 (3.16)	0.47 (3.63)

Statistical Analysis 1 for Change from baseline to Week 12, expressed as a ratio, in number of differential sputum eosinophils

Groups^[1]	All groups
Method^[3]	Other [Repeated measures analysis]
P-Value^[4]	0.6334
Other^[5]	0.57
95% Confidence Interval	( 0.06 to 6.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of change from baseline, expressed as a ratio, in differential sputum eosinophils; Tralo 300 mg Q2W vs placebo.
[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:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Change from baseline to Week 12, expressed as a ratio, in blood free eosinophil cationic protein (ECP) concentrations [ Time Frame: Baseline (Week 0) and Week 12 ]

Measure Type	Secondary
Measure Name	Change from baseline to Week 12, expressed as a ratio, in blood free eosinophil cationic protein (ECP) concentrations
Measure Description	ECP concentrations were determined to assess evidence of activation of eosinophils in blood. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in blood free ECP concentrations is presented as geometric mean ± SD of log values.
Time Frame	Baseline (Week 0) and Week 12
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 FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Measured Values

	Tralo 300 mg Q2W	Placebo
Number of Participants Analyzed [units:participants]	24	28
Change from baseline to Week 12, expressed as a ratio, in blood free eosinophil cationic protein (ECP) concentrations [units: Ratio] Geometric Mean (Standard Deviation)	1.07 (0.40)	0.92 (0.47)

Statistical Analysis 1 for Change from baseline to Week 12, expressed as a ratio, in blood free eosinophil cationic protein (ECP) concentrations

Groups^[1]	All groups
Method^[3]	Other [Repeated measures analysis]
P-Value^[4]	0.3769
Other^[5]	1.11
95% Confidence Interval	( 0.88 to 1.40 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of change from baseline, expressed as a ratio, in blood free ECP concentration; Tralo 300 mg Q2W vs placebo.
[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:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Change from baseline to Week 12, expressed as a ratio, in sputum free ECP concentrations [ Time Frame: Baseline (Week 0) and Week 12 ]

Measure Type	Secondary
Measure Name	Change from baseline to Week 12, expressed as a ratio, in sputum free ECP concentrations
Measure Description	ECP concentrations were determined to assess evidence of activation of eosinophils in sputum. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in sputum free ECP concentrations is presented as geometric mean ± SD of log values.
Time Frame	Baseline (Week 0) and Week 12
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 FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Measured Values

	Tralo 300 mg Q2W	Placebo
Number of Participants Analyzed [units:participants]	16	17
Change from baseline to Week 12, expressed as a ratio, in sputum free ECP concentrations [units: Ratio] Geometric Mean (Standard Deviation)	0.66 (1.21)	1.83 (1.41)

Statistical Analysis 1 for Change from baseline to Week 12, expressed as a ratio, in sputum free ECP concentrations

Groups^[1]	All groups
Method^[3]	Other [Repeated measures analysis]
P-Value^[4]	0.1126
Other^[5]	0.49
95% Confidence Interval	( 0.20 to 1.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of change from baseline, expressed as a ratio, in sputum free ECP concentration; Tralo 300 mg Q2W vs placebo.
[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:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	12 weeks
Additional Description	Data is reported for adverse events during the treatment period (onset date ≥ the first day of IP and ≤ the last day of IP + 2 weeks). Patient population was the safety analysis set which included all patients who received any IP, classified according to the treatment they actually received.

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Serious Adverse Events

Tralo 300 mg Q2W

Placebo

Total, serious adverse events

# participants affected / at risk

0/39 (0.00%)

1/40 (2.50%)

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/39 (0.00%)

1/40 (2.50%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

Other Adverse Events

Time Frame	12 weeks
Additional Description	Data is reported for adverse events during the treatment period (onset date ≥ the first day of IP and ≤ the last day of IP + 2 weeks). Patient population was the safety analysis set which included all patients who received any IP, classified according to the treatment they actually received.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Tralo 300 mg Q2W	Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).
Placebo	Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses).

Other Adverse Events

Tralo 300 mg Q2W

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

30/39 (76.92%)

27/40 (67.50%)

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

8/39 (20.51%)

17/40 (42.50%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

2/39 (5.13%)

9/40 (22.50%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/39 (7.69%)

2/40 (5.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/39 (5.13%)

1/40 (2.50%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

General disorders

Injection site erythema¹,^†

# participants affected / at risk

3/39 (7.69%)

0/40 (0.00%)

# events

General disorders

Injection site pain¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

General disorders

Injection site pruritus¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

General disorders

Injection site swelling¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

General disorders

Non-cardiac chest pain¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

1/39 (2.56%)

3/40 (7.50%)

# events

Investigations

Weight increased¹,^†

# participants affected / at risk

2/39 (5.13%)

1/40 (2.50%)

# events

Injury, poisoning and procedural complications

Procedural pain¹,^†

# participants affected / at risk

0/39 (0.00%)

3/40 (7.50%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

6/39 (15.38%)

2/40 (5.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

3/39 (7.69%)

2/40 (5.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

3/39 (7.69%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

2/39 (5.13%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

2/39 (5.13%)

0/40 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

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:

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
The results for differential sputum eosinophils and sputum free ECP levels should be viewed cautiously due to the small sample size and wide variability in results for sputum analyses.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	+1 301-398-0582
E-mail:	[email protected]

Documents available

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Download
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Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Christopher Brightling

Institute for Lung Health, United Kingdom

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3064&filename=d2210c00014-sap-redacted2019.pdf

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3064&filename=d2210c00014-csp-Redacted2019.pdf

Trial Results Summaries