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Clinical Trial Results:
A Phase 2a, Randomized, Double-blind, Placebo-controlled, Parallel-arm, Multicenter Study to Evaluate the Efficacy and Safety of CAT-354, a Recombinant Human Monoclonal Antibody Directed against Interleukin-13 (IL-13), on Asthma Control in Adults with Uncontrolled, Moderate-to-severe, Persistent Asthma

Summary
EudraCT number	2008-007844-33
Trial protocol	DE GB BG
Global end of trial date	03 Aug 2010

Results information
Results version number	v1(current)
This version publication date	11 May 2016
First version publication date	11 May 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MI-CP199

ISRCTN number

US NCT number

NCT00873860

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

Milstein Building, Granta Park, Cambridge, United Kingdom, CB21 6GH

Public contact

Rene van de Merwe, Senior Director, Clinical Development, MedImmune, LLC., vandermerwer@medimmune.com

Scientific contact

Rene van de Merwe, Senior Director, Clinical Development, MedImmune, LLC., vandermerwer@medimmune.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Aug 2010

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Aug 2010

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the effect of 3 subcutaneous (SC) treatment regimens of CAT-354 versus placebo on asthma control at Study Day 92 in adults with uncontrolled, moderate-to-severe, persistent asthma.

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Jun 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 37

Country: Number of subjects enrolled

Romania: 77

Country: Number of subjects enrolled

Bulgaria: 52

Country: Number of subjects enrolled

Germany: 21

Country: Number of subjects enrolled

United Kingdom: 7

Worldwide total number of subjects

194

EEA total number of subjects

194

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

194

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 357 participants were screened in this study, out of which 194 participants were enrolled and randomized.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Arm type

Placebo

Investigational medicinal product name

Placebo matched to CAT-354

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

CAT-354 150 mg

Arm description

CAT-354 150 milligram (mg) subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Arm type

Experimental

Investigational medicinal product name

CAT-354

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received CAT-354 150 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

CAT-354 300 mg

Arm description

CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Arm type

Experimental

Investigational medicinal product name

CAT-354

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

CAT-354 600 mg

Arm description

CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Arm type

Experimental

Investigational medicinal product name

CAT-354

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Number of subjects in period 1	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Started	48	47	51	48
Treated	47	47	51	48
Completed	44	47	48	47
Not completed	4	0	3	1
Adverse event, serious fatal	1	-	-	-
Consent withdrawn by subject	1	-	2	-
Unspecified	1	-	1	-
Lost to follow-up	1	-	-	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 150 mg

Reporting group description

CAT-354 150 milligram (mg) subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 300 mg

Reporting group description

CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 600 mg

Reporting group description

CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg	Total
Number of subjects	48	47	51	48	194
Age categorical
Units: Subjects
Adults (18-64 years)	48	47	51	48	194
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	47.2 ± 9.8	43.4 ± 11.1	48.7 ± 11	49.8 ± 10.4	-
Gender, Male/Female
Units: participants
Female	33	19	36	28	116
Male	15	28	15	20	78

End points

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Reporting group title

Placebo

Reporting group description

Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 150 mg

Reporting group description

CAT-354 150 milligram (mg) subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 300 mg

Reporting group description

CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 600 mg

Reporting group description

CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Primary: Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92

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End point title

Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92

End point description

ACQ is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued prior to receiving 4 doses due to safety reasons. Here, ‘n’ signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.

End point type

Primary

End point timeframe

Day 1 (baseline), Day 92

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: units on a scale
arithmetic mean (standard deviation)
Day 1 (n=46, 46, 50, 47)	2.63 ± 0.51	2.72 ± 0.58	2.62 ± 0.5	2.72 ± 0.76
Change at Day 92 (n= 46, 46, 51, 47)	-0.61 ± 0.9	-0.73 ± 1.12	-0.7 ± 0.93	-0.86 ± 1.09

Statistical analysis 1

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.573 ^[1]

Method

ANOVA

Confidence interval

Notes
[1] - Change at Day 92: p-value was based on analysis of variance (ANOVA).

Statistical analysis 2

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.64 ^[2]

Method

ANOVA

Confidence interval

Notes
[2] - Change at Day 92: p-value was based on ANOVA.

Statistical analysis 3

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.224 ^[3]

Method

ANOVA

Confidence interval

Notes
[3] - Change at Day 92: p-value was based on ANOVA.

Secondary: Time to First Observed Asthma Control

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End point title

Time to First Observed Asthma Control

End point description

Time to first asthma control defined as number of days from Study Day 1 to the post-baseline ACQ score measurement time point when greater than or equal to (>=) 0.5 reduction from baseline in mean ACQ score was first observed. Time to first asthma control was analyzed from Day 1 through Day 92 and up to entire study duration through Day 169. The ACQ score is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons.

End point type

Secondary

End point timeframe

Day 1 to Day 92 and Day 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: days
median (confidence interval 95%)
Day 1 to 92	25.5 (15 to 71)	22 (15 to 43)	15 (15 to 43)	15 (15 to 36)
Day 1 to 169	25.5 (15 to 71)	22 (15 to 43)	15 (15 to 43)	15 (15 to 36)

Statistical analysis 1

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4686 ^[4]

Method

Logrank

Confidence interval

Notes
[4] - Day 1 to 92: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 2

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.317 ^[5]

Method

Logrank

Confidence interval

Notes
[5] - Day 1 to 92: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 3

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1664 ^[6]

Method

Logrank

Confidence interval

Notes
[6] - Day 1 to 92: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 4

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3234 ^[7]

Method

Logrank

Confidence interval

Notes
[7] - Day 1 to 169: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 5

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3133 ^[8]

Method

Logrank

Confidence interval

Notes
[8] - Day 1 to 169: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 6

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2108 ^[9]

Method

Logrank

Confidence interval

Notes
[9] - Day 1 to 169: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Secondary: Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites at Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169

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End point title

Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites at Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169

End point description

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Spirometry was performed with the participant in the sitting/standing (kept consistent at each visit) position at study sites by the investigator or qualified designee according to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. Multiple forced expiratory efforts (at least 3 but no more than 8) were performed for each office spirometry session and the 2 best efforts that met ATS/ERS acceptability and reproducibility criteria were recorded. The best efforts were based on the highest FEV1. The maximum FEV1 of the 2 best efforts was used for the analysis. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons.Here, ''n'' signifies participants evaluable for specified category for each arm, respectively.

End point type

Secondary

End point timeframe

Day 1 (baseline), 15, 29, 43, 57, 71, 85, 92, 127 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: liters
arithmetic mean (standard deviation)
Day 1 (n=46,46,51,47)	1.949 ± 0.479	2.178 ± 0.661	1.907 ± 0.586	1.977 ± 0.646
Change at Day 15 (n=44,46,50,46)	0.019 ± 0.42	0.122 ± 0.316	0.116 ± 0.378	0.134 ± 0.348
Change at Day 29 (n=46,46,49,47)	0.051 ± 0.424	0.138 ± 0.315	0.149 ± 0.303	0.222 ± 0.354
Change at Day 43 (n=45,44,47,47)	0.125 ± 0.399	0.131 ± 0.38	0.164 ± 0.358	0.147 ± 0.373
Change at Day 57 (n=45,46,49,47)	0.043 ± 0.436	0.127 ± 0.339	0.187 ± 0.349	0.201 ± 0.344
Change at Day 71 (n=45,45,49,47)	0.047 ± 0.397	0.158 ± 0.314	0.179 ± 0.381	0.19 ± 0.335
Change at Day 85 (n=45,46,48,47)	0.087 ± 0.397	0.135 ± 0.342	0.286 ± 0.393	0.265 ± 0.473
Change at Day 92 (n=42,44,49,44)	0.063 ± 0.476	0.158 ± 0.348	0.211 ± 0.374	0.262 ± 0.408
Change at Day 127 (n=44,44,49,47)	0.094 ± 0.489	0.144 ± 0.263	0.241 ± 0.381	0.237 ± 0.285
Change at Day 169 (n=42,42,47,47)	0.101 ± 0.442	0.204 ± 0.378	0.211 ± 0.394	0.236 ± 0.366

No statistical analyses for this end point

Secondary: Change From Baseline in Peak Expiratory Flow (PEF) Recorded at Home Every Week From Day 1 to 169

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End point title

Change From Baseline in Peak Expiratory Flow (PEF) Recorded at Home Every Week From Day 1 to 169

End point description

The PEF is a participant’s maximum speed of expiration, as measured with a peak flow meter. Home peak flow testing for PEF was performed every morning while sitting or standing prior to using any medication (if needed) for asthma. Mean of the data was collected over 1 week prior to dosing on Day 1 was considered as baseline. Mean PEF values for each week were used to calculate the change from baseline values starting from Day 2 to 169. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

End point type

Secondary

End point timeframe

Day -7 to 1 (predose), Day 2 to 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: liters/minute
arithmetic mean (standard deviation)
Day -7 to 1 (n=46,46,51,47)	282.63 ± 100.65	351.06 ± 130.41	291.54 ± 119.46	325.23 ± 123.9
Change in Day 2 to 8 (n=44,46,51,47)	-5.77 ± 22.74	1.91 ± 23.81	-4.53 ± 19.02	5.94 ± 29.93
Change in Day 9 to 15 (n=45,46,51,47)	-7.46 ± 29.68	-4.1 ± 28.15	-2.83 ± 24.4	5.75 ± 42.34
Change in Day 16 to 22 (n=45,46,51,47)	-8.94 ± 35.72	-6.53 ± 32.7	-0.37 ± 33.85	10.55 ± 51.26
Change in Day 23 to 29 (n=44,46,51,47)	-10.53 ± 40.06	-6.61 ± 37.95	-0.79 ± 36.94	10.61 ± 52.64
Change in Day 30 to 36 (n=45,46,51,47)	-5.69 ± 44.69	-5.69 ± 41.87	-1.98 ± 36.06	6.52 ± 50.15
Change in Day 37 to 43 (n=44,46,50,47)	-11.08 ± 41.52	-2 ± 49.76	-4.07 ± 39.8	5.55 ± 54.28
Change in Day 44 to 50 (n=44,46,50,47)	-6.37 ± 41.5	-9.02 ± 47.51	-5.3 ± 36.57	-0.84 ± 50.67
Change in Day 51 to 57 (n=45,46,50,47)	-7 ± 41.7	-6.01 ± 47.36	-4.85 ± 41.27	-3.57 ± 52.84
Change in Day 58 to 64 (n=45,46,50,46)	-9.84 ± 38.73	-2.83 ± 47.42	-1.42 ± 41.9	-0.73 ± 55.98
Change in Day 65 to 71 (n=45,46,50,46)	-11.81 ± 43.87	-3.98 ± 47.2	-0.92 ± 49.95	-1.82 ± 49.79
Change in Day 72 to 78 (n=44,45,50,47)	-3.72 ± 44.07	-3.42 ± 53.55	2.54 ± 45.58	1.78 ± 49.45
Change in Day 79 to 85 (n=45,45,50,46)	-10.83 ± 43.99	-6.67 ± 54.49	-0.35 ± 40.29	5.3 ± 60.62
Change in Day 86 to 92 (n=45,46,50,47)	-3.26 ± 47.36	-6.66 ± 51.23	5.04 ± 40.52	0.31 ± 62.86
Change in Day 93 to 99 (n=45,46,50,47)	-2.52 ± 47.94	-4.99 ± 49.91	5.16 ± 40.99	7.81 ± 58.29
Change in Day 100 to 106 (n=44,46,49,47)	-9.6 ± 55.47	-7.33 ± 52.64	1.93 ± 43.08	2 ± 62.18
Change in Day 107 to 113 (n=44,45,48,47)	-7.53 ± 56.29	-11.29 ± 57.33	0.53 ± 45.6	0.39 ± 61.52
Change in Day 114 to 120 (n=42,45,47,47)	-2.19 ± 61.74	-8.97 ± 55.61	4.85 ± 39.54	-3.03 ± 59.68
Change in Day 121 to 127 (n=42,46,46,46)	-3.58 ± 65.64	-8.99 ± 64.6	3.61 ± 46.18	-4.21 ± 57.88
Change in Day 128 to 134 (n=42,45,45,47)	-4.39 ± 61.22	-14.81 ± 61.39	4.62 ± 44.65	-2.64 ± 56.87
Change in Day 135 to 141 (n=40,45,47,47)	-0.26 ± 58.83	-17.03 ± 58.99	1.11 ± 44.36	-6.03 ± 63.13
Change in Day 142 to 148 (n=40,45,47,47)	5.16 ± 66.54	-11.63 ± 61.02	-2.69 ± 51.65	-9.65 ± 65.62
Change in Day 149 to 155 (n=40,45,46,47)	0.43 ± 60.53	-9.56 ± 60.13	-7.65 ± 47.44	-11.07 ± 62.16
Change in Day 156 to 162 (n=40,45,46,46)	-1.38 ± 65.53	-11.6 ± 62.14	-10.05 ± 43.11	-10.68 ± 66.86
Change in Day 163 to 169 (n=37,41,42,40)	-0.36 ± 58.66	-5.68 ± 60.69	-4.71 ± 49.29	-3.23 ± 66.84

No statistical analyses for this end point

Secondary: Number of Puffs of Rescue Beta-2 Agonist Per Week

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End point title

Number of Puffs of Rescue Beta-2 Agonist Per Week

End point description

Number of Puffs of Rescue Beta-2 Agonist Per Week Rescue beta-2 agonist use (total number of puffs for the preceding week) was collected daily in the morning by the participants in the daily diary provided to them. Average values for each week were reported starting from Day -7 to Day 169. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

End point type

Secondary

End point timeframe

Day -7 to 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: puffs per week
arithmetic mean (standard deviation)
Day -7 to 1 (n=46,46, 51,47)	2.58 ± 1.7	2.84 ± 2.03	2.04 ± 1.51	2.62 ± 1.96
Day 2 to 8 (n=45,46, 51,47)	2.5 ± 1.8	2.4 ± 2	1.9 ± 1.5	2.3 ± 2
Day 9 to 15 (n=46,46, 51,47)	2.4 ± 1.8	2.5 ± 2.3	1.9 ± 1.5	2.2 ± 2
Day 16 to 22 (n=46,46, 51,47)	2.6 ± 1.9	2.2 ± 2	1.9 ± 1.7	2.3 ± 2.2
Day 23 to 29 (n=45,46, 51,47)	2.7 ± 2.1	2.2 ± 2	2 ± 1.9	2.2 ± 2.1
Day 30 to 36 (n=46,46, 51,47)	2.5 ± 2	2.1 ± 2.2	1.9 ± 2	2 ± 1.9
Day 37 to 43 (n=45,46, 50,47)	2.4 ± 2	2.1 ± 2.2	1.9 ± 2	2 ± 2
Day 44 to 50 (n=45,46, 50,47)	2.5 ± 2	1.9 ± 2.2	1.7 ± 2	2 ± 2
Day 51 to 57 (n=45,46, 50,47)	2.5 ± 2.1	2 ± 2	1.8 ± 1.9	2 ± 2.1
Day 58 to 64 (n=46,46, 49,46)	2.5 ± 2.2	1.9 ± 2	1.9 ± 2	1.8 ± 2
Day 65 to 71 (n=46,46, 50,47)	2.7 ± 2.3	2 ± 2	1.8 ± 2	2 ± 1.9
Day 72 to 78 (n=45,45, 50,46)	2.5 ± 2.2	2 ± 2	1.8 ± 2.1	1.9 ± 1.8
Day 79 to 85 (n=46,46, 50,46)	2.6 ± 2.3	2.1 ± 2.1	1.9 ± 2	1.8 ± 1.8
Day 86 to 92 (n=46,46, 50,47)	2.5 ± 2.3	2 ± 2.1	1.8 ± 2	1.7 ± 1.7
Day 93 to 99 (n=46,46, 50,47)	2.4 ± 2.2	1.7 ± 2	1.8 ± 2.1	1.6 ± 1.8
Day 100 to 106 (n=45,46, 49,47)	2.3 ± 2.1	1.9 ± 2.2	1.7 ± 2.2	1.8 ± 1.8
Day 107 to 113 (n=45,45, 48,47)	2.4 ± 2.1	1.9 ± 2.2	1.7 ± 1.9	1.7 ± 1.6
Day 114 to 120 (n=43,45, 47,47)	2.3 ± 2	1.9 ± 2.1	1.7 ± 1.9	1.7 ± 1.7
Day 121 to 127 (n=43,46, 46,47)	2.2 ± 1.9	1.9 ± 2.2	1.8 ± 2	1.6 ± 1.6
Day 128 to 134 (n=44,45, 47,47)	2.2 ± 2.1	1.8 ± 2	1.6 ± 1.9	1.6 ± 1.7
Day 135 to 141 (n=42,45, 47,47)	2.2 ± 2	1.9 ± 1.9	1.7 ± 2	1.7 ± 1.8
Day 142 to 148 (n=42,45, 47,47)	2.3 ± 2	1.9 ± 2.1	1.8 ± 2	1.8 ± 1.8
Day 149 to 155 (n=42,45, 46,47)	2.4 ± 2.2	1.9 ± 2.1	1.8 ± 2	1.8 ± 1.8
Day 156 to 162 (n=42,45, 46,46)	2.3 ± 2.1	1.9 ± 2.1	1.7 ± 2.2	2 ± 2
Day 163 to 169 (n=39,41,42,40)	2.7 ± 2.6	1.9 ± 2.1	1.6 ± 1.8	1.7 ± 1.9

No statistical analyses for this end point

Secondary: Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores

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End point title

Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores

End point description

AQLQ[S]: a 32-item questionnaire that measures the functional impairments experienced by adult participants including 4 domains (Symptoms, Activity Limitations, Emotional Function, and Environmental Stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

End point type

Secondary

End point timeframe

Day 1, 29, 57, 92, 127 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: units on a scale
arithmetic mean (standard deviation)
Overall : Day 1 (n=41,41,44,39)	4.22 ± 0.83	3.96 ± 0.89	4.12 ± 0.8	4.11 ± 0.94
Overall: Day 29 (n=43,41,44,40)	4.39 ± 1.04	4.39 ± 1.01	4.47 ± 0.97	4.6 ± 0.91
Overall: Day 57 (n=44,40,43,45)	4.57 ± 1.03	4.56 ± 1.15	4.47 ± 1.05	4.73 ± 0.96
Overall: Day 92 (n=40,42,40,38)	4.7 ± 1.16	4.88 ± 1.31	4.74 ± 1.15	4.87 ± 0.99
Overall: Day 127 (n=41,42,44,42)	4.69 ± 1.22	4.76 ± 1.29	4.64 ± 1.11	4.85 ± 1.13
Overall: Day 169 (n=41,44,45,44)	4.72 ± 1.29	4.73 ± 1.26	4.61 ± 1.27	4.76 ± 1.13
Symptom: Day 1 (n=41,41,44,39)	4.15 ± 0.88	3.89 ± 0.84	4.11 ± 0.71	4.08 ± 1.06
Symptom: Day 29 (n=43,41,44,40)	4.32 ± 1.08	4.44 ± 1.07	4.48 ± 0.94	4.56 ± 1.01
Symptom: Day 57 (n=44,40,43,45)	4.61 ± 1.02	4.68 ± 1.23	4.49 ± 1.05	4.73 ± 1.05
Symptom: Day 92 (n=40,42,40,38)	4.77 ± 1.17	4.88 ± 1.4	4.78 ± 1.17	4.92 ± 1.01
Symptom: Day 127 (n=41,42,44,42)	4.74 ± 1.33	4.79 ± 1.31	4.69 ± 1.09	4.95 ± 1.31
Symptom: Day 169 (n=41,44,45,44)	4.82 ± 1.3	4.76 ± 1.29	4.63 ± 1.26	4.77 ± 1.31
Activity Limitation: Day 1 (n=41,41,44,39)	4.38 ± 0.83	4.07 ± 0.88	4.13 ± 0.97	4.15 ± 0.91
Activity Limitation: Day 29 (n=43,41,44,40)	4.47 ± 1	4.37 ± 1.07	4.42 ± 1.08	4.59 ± 0.92
Activity Limitation: Day 57 (n=44,40,43,45)	4.57 ± 1.03	4.42 ± 1.09	4.41 ± 1.14	4.74 ± 0.99
Activity Limitation: Day 92 (n=40,42,40,38)	4.68 ± 1.19	4.89 ± 1.29	4.73 ± 1.15	4.91 ± 1.04
Activity Limitation: Day 127 (n=41,42,44,42)	4.64 ± 1.2	4.77 ± 1.32	4.62 ± 1.13	4.66 ± 1.08
Activity Limitation: Day 169 (n=41,44,45,44)	4.68 ± 1.28	4.76 ± 1.26	4.54 ± 1.31	4.7 ± 1.14
Emotional Function: Day 1 (n=41,41,44,39)	4.3 ± 1.08	4.2 ± 1.18	4.45 ± 1.1	4.29 ± 1.24
Emotional Function: Day 29 (n=43,41,44,40)	4.64 ± 1.27	4.82 ± 1.17	4.82 ± 1.22	4.88 ± 1.17
Emotional Function: Day 57 (n=44,40,43,45)	4.85 ± 1.36	4.98 ± 1.42	4.87 ± 1.24	4.99 ± 1.13
Emotional Function: Day 92 (n=40,42,40,38)	5 ± 1.31	5.24 ± 1.33	4.99 ± 1.45	4.98 ± 1.02
Emotional Function: Day 127 (n=41,42,44,42)	5.08 ± 1.4	5.06 ± 1.48	4.98 ± 1.4	5.28 ± 1.29
Emotional Function: Day 169 (n=41,44,45,44)	5.05 ± 1.56	5 ± 1.5	5.06 ± 1.39	5.13 ± 1.28
Environment stimuli: Day 1 (n=41,41,44,39)	3.88 ± 1.28	3.55 ± 1.43	3.7 ± 1.11	3.85 ± 1.1
Environment stimuli: Day 29 (n=43,41,44,40)	4.06 ± 1.26	3.75 ± 1.48	4.13 ± 1.41	4.4 ± 1.2
Environment stimuli: Day 57 (n=44,40,43,45)	4.07 ± 1.34	4.04 ± 1.36	4.09 ± 1.43	4.37 ± 1.49
Environment stimuli: Day 92 (n=40,42,40,38)	4.16 ± 1.56	4.44 ± 1.63	4.31 ± 1.43	4.47 ± 1.47
Environment stimuli: Day 127 (n=41,42,44,42)	4.18 ± 1.58	4.3 ± 1.57	4.15 ± 1.56	4.51 ± 1.64
Environment stimuli: Day 169 (n=41,44,45,44)	4.13 ± 1.54	4.26 ± 1.5	4.18 ± 1.76	4.45 ± 1.51

No statistical analyses for this end point

Secondary: Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores at Day 29, 57, 92, 127 and 169

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End point title

Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores at Day 29, 57, 92, 127 and 169

End point description

AQLQ[S]: a 32-item questionnaire that measures the functional impairments experienced by adult participants including 4 domains (Symptoms, Activity Limitations, Emotional Function, and Environmental Stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score calculated as mean response to all questions. The 4 domain scores were means of the responses to questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data collected on Day 1 prior to dosing considered as baseline. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons. Here, 'n' signifies participants who were evaluable at specified time points for each group, respectively.

End point type

Secondary

End point timeframe

Day 1, 29, 57, 92, 127 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: units on a scale
arithmetic mean (standard deviation)
Overall: Day 29 (n=34,35,37,31)	0.32 ± 0.65	0.38 ± 0.64	0.39 ± 0.88	0.66 ± 0.76
Overall: Day 57 (n=33,33,35,34)	0.45 ± 0.77	0.7 ± 0.99	0.38 ± 0.95	0.77 ± 1.04
Overall: Day 92 (n=31,34,35,27)	0.63 ± 0.88	0.94 ± 1.21	0.52 ± 1.07	1.05 ± 1.25
Overall: Day 127 (n=32,36,34,31)	0.71 ± 0.85	0.78 ± 1.21	0.49 ± 1.14	1.05 ± 1.15
Overall: Day 169 (n=31,37,37,34)	0.64 ± 1.05	0.78 ± 1.19	0.56 ± 1.09	0.75 ± 1.26
Symptom: Day 29 (n=34,35,37,31)	0.31 ± 0.81	0.49 ± 0.83	0.43 ± 0.83	0.62 ± 0.8
Symptom: Day 57 (n=33,33,35,34)	0.52 ± 0.86	0.87 ± 1.1	0.44 ± 0.85	0.81 ± 1.11
Symptom: Day 92 (n=31,34,35,27)	0.76 ± 1	1 ± 1.32	0.61 ± 1.11	1.14 ± 1.39
Symptom: Day 127 (n=32,36,34,31)	0.85 ± 1.03	0.87 ± 1.24	0.56 ± 1.14	1.24 ± 1.23
Symptom: Day 169 (n=31,37,37,34)	0.8 ± 1.06	0.86 ± 1.22	0.62 ± 1.17	0.77 ± 1.34
Activity Limitation: Day 29 (n=34,35,37,31)	0.21 ± 0.64	0.25 ± 0.69	0.32 ± 0.96	0.57 ± 0.9
Activity Limitation: Day 57 (n=33,33,35,34)	0.28 ± 0.79	0.44 ± 0.89	0.3 ± 1.08	0.71 ± 1.07
Activity Limitation: Day 92 (n=31,34,35,27)	0.42 ± 0.81	0.8 ± 1.12	0.51 ± 1.12	1.04 ± 1.26
Activity Limitation: Day 127 (n=32,36,34,31)	0.43 ± 0.77	0.65 ± 1.2	0.45 ± 1.14	0.72 ± 1.28
Activity Limitation: Day 169 (n=31,37,37,34)	0.38 ± 1.09	0.68 ± 1.16	0.44 ± 1.09	0.65 ± 1.37
Emotional Function: Day 29 (n=34,35,37,31)	0.5 ± 0.93	0.57 ± 0.76	0.36 ± 1.04	0.86 ± 0.97
Emotional Function: Day 57 (n=33,33,35,34)	0.69 ± 1.15	0.95 ± 1.16	0.42 ± 1.15	0.86 ± 1.21
Emotional Function: Day 92 (n=31,34,35,27)	0.87 ± 1.25	1.06 ± 1.25	0.43 ± 1.26	0.93 ± 1.39
Emotional Function: Day 127 (n=32,36,34,31)	1.02 ± 1.2	0.87 ± 1.38	0.41 ± 1.32	1.32 ± 1.42
Emotional Function: Day 169 (n=31,37,37,34)	0.88 ± 1.42	0.88 ± 1.36	0.63 ± 1.2	0.95 ± 1.4
Environmental Stimuli: Day 29 (n=34,35,37,31)	0.4 ± 0.85	0.16 ± 0.78	0.47 ± 1.18	0.76 ± 0.8
Environmental Stimuli: Day 57 (n=33,33,35,34)	0.36 ± 0.86	0.58 ± 1.39	0.38 ± 1.27	0.65 ± 1.4
Environmental Stimuli: Day 92 (n=31,34,35,27)	0.54 ± 0.94	0.97 ± 1.68	0.42 ± 1.17	0.94 ± 1.28
Environmental Stimuli: Day 127 (n=32,36,34,31)	0.64 ± 1.11	0.74 ± 1.68	0.48 ± 1.45	1.02 ± 1.22
Environmental Stimuli: Day 169 (n=31,37,37,34)	0.52 ± 1.17	0.75 ± 1.55	0.58 ± 1.3	0.74 ± 1.39

No statistical analyses for this end point

Secondary: Patient Global Impression of Change (PGIC)

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End point title

Patient Global Impression of Change (PGIC)

End point description

Patient Global Impression of Change (PGIC): participant rated instrument to measure participant's change in overall status compared to baseline on a 7-point scale; range from 1 (very much worse) to 7 (very much better). Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

End point type

Secondary

End point timeframe

Day 92 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: units on a scale
arithmetic mean (standard deviation)
Day 92 (n=40,42,40,38)	5.1 ± 1.1	5.3 ± 1.1	5.3 ± 1	5.2 ± 1.2
Day 169 (n=42,44,45,44)	5.1 ± 1.1	5.3 ± 1.1	5 ± 1	5.1 ± 1.3

No statistical analyses for this end point

Secondary: Percentage of Participants with Mean Asthma Control Questionnaire (ACQ) Score Less Than or Equal to 0.75 or ACQ Score Greater Than 0.75 but Less Than 1.5

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End point title

Percentage of Participants with Mean Asthma Control Questionnaire (ACQ) Score Less Than or Equal to 0.75 or ACQ Score Greater Than 0.75 but Less Than 1.5

End point description

Percentage of participants with mean ACQ score less than or equal to (<=) 0.75 or mean ACQ score greater than (>) 0.75 and less than (<) 1.5 were analyzed. The ACQ is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score is the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Mean ACQ scores of less than or equal to (<=) 0.75 indicated well-controlled asthma, mean ACQ scores greater than (>) 0.75 but less than (<) 1.5 indicated partly controlled asthma. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons.

End point type

Secondary

End point timeframe

Day 92 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: percentage of participants
number (not applicable)
ACQ score<=0.75: Day 92	13	19.6	11.8	17
ACQ score>0.75 and <1.5: Day 92	15.2	13	15.7	19.1
ACQ score<=0.75: Day 169	13	19.6	13.7	19.1
ACQ score>0.75 and <1.5: Day 169	21.7	10.9	17.6	19.1

Statistical analysis 2

Comparison groups

Placebo v CAT-354 150 mg v CAT-354 300 mg v CAT-354 600 mg

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.592 ^[10]

Method

Fisher exact

Confidence interval

Notes
[10] - ACQ score <=0.75, Day 169: Fisher exact test was used to compare all arms.

Statistical analysis 1

Comparison groups

Placebo v CAT-354 150 mg v CAT-354 300 mg v CAT-354 600 mg

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.934 ^[11]

Method

Fisher exact

Confidence interval

Notes
[11] - ACQ score <=0.75, Day 92: Fisher exact test was used to compare all arms.

Secondary: Serum Concentration for CAT-354

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End point title

Serum Concentration for CAT-354 ^[12]

End point description

Pharmacokinetic (PK) population included participants who received CAT-354 and had a sufficient number of serum concentration measurements for computing PK parameters. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

End point type

Secondary

End point timeframe

Predose on Day 15, 29, 43, 57, 71 and 85; Day 88, 92, 99, 127, and 169

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No inferential statistical analysis was planned for this end-point

End point values	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	47	51	48
Units: microgram per milliliter (mcg/mL)
arithmetic mean (standard deviation)
Day 15 (n=46,48,48)	14.5 ± 5.57	27.8 ± 10.3	56.4 ± 16
Day 29 (n=45,51,47)	20.8 ± 7.2	40.2 ± 15	81.9 ± 23.5
Day 43 (n=46,50,47)	26.9 ± 12.7	51 ± 16	98.5 ± 33.4
Day 57 (n=46,48,46)	28.4 ± 11.3	58.8 ± 20.2	108 ± 35.8
Day 71 (n=46,49,47)	29.3 ± 11.9	61 ± 21.4	112 ± 41.2
Day 85 (n=45,49,47)	31.1 ± 12.5	62 ± 23.8	120 ± 44.5
Day 88 (n=46,48,45)	43.4 ± 15.8	85.7 ± 32.7	157 ± 56.5
Day 92 (n=45,46,45)	42 ± 16.3	86.8 ± 33.1	156 ± 46.6
Day 99 (n=46,50,46)	31.3 ± 13	69.3 ± 27.2	125 ± 41.9
Day 127 (n=47,48,47)	11.5 ± 6.02	22.9 ± 12	43.7 ± 20.5
Day 169 (n=47,48,46)	2.94 ± 2.23	5.87 ± 3.69	10.1 ± 6.71

No statistical analyses for this end point

Secondary: Number of Participants With Anti-Drug Antibodies to CAT-354 at any Visit

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End point title

Number of Participants With Anti-Drug Antibodies to CAT-354 at any Visit

End point description

Safety population included all participants who received any dose of the investigational product. Here, ‘N’(number of participants analyzed) signifies those participants who were evaluable for this measure.

End point type

Secondary

End point timeframe

Day 1, 92 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	47	47	49	47
Units: participants	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Participants With Positive Serum Antibodies to CAT-354 at any Visit

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End point title

Percentage of Participants With Positive Serum Antibodies to CAT-354 at any Visit

End point description

End point type

Secondary

End point timeframe

Day 1, 92 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	47	47	49	47
Units: percentage of participants	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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End point title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

End point description

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state. Safety population included all participants who received any dose of the investigational product.

End point type

Secondary

End point timeframe

Day 1 to 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	47	47	51	48
Units: participants
TEAEs	17	20	25	25
TESAEs	3	2	0	1

No statistical analyses for this end point

Secondary: Percentage of Participants With at least 1 Moderate or Severe Exacerbation

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End point title

Percentage of Participants With at least 1 Moderate or Severe Exacerbation

End point description

Asthma exacerbation was defined as either a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) or a reduction of >= 20 percent (%) in PEF or FEV1 from baseline that did not resolve after the initiation of rescue medications and resulted in an administration of systemic corticosteroids by the investigator or health care provider. Asthma exacerbation severity was classified as: 1) Moderate-worsening symptoms that required systemic corticosteroids. 2) Severe-worsening symptoms that required systemic corticosteroids and hospital admission. No separate analyses were performed for moderate and severe exacerbations since only 1 participant had a severe exacerbation. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued prior to receiving 4 doses due to safety reasons.

End point type

Secondary

End point timeframe

Day 92 and 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: Percentage of Participants
number (not applicable)
Day 92	4.3	2.2	2	4.3
Day 169	4.3	4.3	3.9	6.4

Statistical analysis 1

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[13]

Method

Fisher exact

Confidence interval

Notes
[13] - Day 92: Fisher exact test was used for the analysis.

Statistical analysis 2

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6022 ^[14]

Method

Fisher exact

Confidence interval

Notes
[14] - Day 92: Fisher exact test was used for the analysis.

Statistical analysis 3

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[15]

Method

Fisher exact

Confidence interval

Notes
[15] - Day 92: Fisher exact test was used for the analysis.

Statistical analysis 4

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[16]

Method

Fisher exact

Confidence interval

Notes
[16] - Day 169: Fisher exact test was used for the analysis.

Statistical analysis 5

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[17]

Method

Fisher exact

Confidence interval

Notes
[17] - Day 169: Fisher exact test was used for the analysis.

Statistical analysis 6

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[18]

Method

Fisher exact

Confidence interval

Notes
[18] - Day 169: Fisher exact test was used for the analysis.

Secondary: Moderate or Severe Asthma Exacerbations per Person per Annum

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End point title

Moderate or Severe Asthma Exacerbations per Person per Annum

End point description

Asthma exacerbation was defined as either a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) or a reduction of >=20% in PEF or FEV1 from baseline that did not resolve after the initiation of rescue medications and resulted in an administration of systemic corticosteroids by the investigator or health care provider. Asthma exacerbation rate, calculated as total asthma exacerbations per person per annum, was assessed based on asthma exacerbation data up to Day 92 and 169 (Rate = mean asthma exacerbations for all participants/X days*365 days, where X = 92 or 169). Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons.

End point type

Secondary

End point timeframe

Day 1 to Day 92 and Day 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: asthma exacerbations/person/annum
arithmetic mean (standard error)
Day 1 to 92	0.26 ± 0.19	0.09 ± 0.09	0.08 ± 0.08	0.25 ± 0.19
Day 1 to 169	0.23 ± 0.19	0.14 ± 0.1	0.08 ± 0.06	0.19 ± 0.11

Statistical analysis 1

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.551 ^[19]

Method

Van Elteren Test

Confidence interval

Notes
[19] - Day 1 to 92: P-value was calculated against placebo group from Van Elteren Test.

Statistical analysis 2

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.492 ^[20]

Method

Van Elteren Test

Confidence interval

Notes
[20] - Day 1 to 92: P-value was calculated against placebo group from Van Elteren Test.

Statistical analysis 3

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.983 ^[21]

Method

Van Elteren Test

Confidence interval

Notes
[21] - Day 1 to 92: P-value was calculated against placebo group from Van Elteren Test.

Statistical analysis 4

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.991 ^[22]

Method

Van Elteren Test

Confidence interval

Notes
[22] - Day 1 to 169: P-value was calculated against placebo group from Van Elteren Test.

Statistical analysis 5

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9 ^[23]

Method

Van Elteren Test

Confidence interval

Notes
[23] - Day 1 to 169: P-value was calculated against placebo group from Van Elteren Test.

Statistical analysis 6

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.673 ^[24]

Method

Van Elteren Test

Confidence interval

Notes
[24] - Day 1 to 169: P-value was calculated against placebo group from Van Elteren Test.

Secondary: Time to First Moderate or Severe Asthma Exacerbation

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End point title

Time to First Moderate or Severe Asthma Exacerbation

End point description

Time to first moderate or severe asthma exacerbation was defined as time to first observed progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) or a reduction of >=20% in PEF or FEV1 from baseline that did not resolve after the initiation of rescue medications and resulted in an administration of systemic corticosteroids by the investigator or health care provider. Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued treatment due to safety reasons.

End point type

Secondary

End point timeframe

Day 1 to Day 92 and Day 169

End point values	Placebo	CAT-354 150 mg	CAT-354 300 mg	CAT-354 600 mg
Number of subjects analysed	46	46	51	47
Units: days
arithmetic mean (standard error)
Day 1 to 92	89.67 ± 1.56	90.43 ± 1.32	88.16 ± 2.12	89.94 ± 1.36
Day 1 to 169	162.24 ± 3.79	163.5 ± 3.24	158.29 ± 4.41	161.21 ± 3.71

Statistical analysis 1

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.546 ^[25]

Method

Logrank

Confidence interval

Notes
[25] - Day 1 to 92: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 2

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.534 ^[26]

Method

Logrank

Confidence interval

Notes
[26] - Day 1 to 92: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 3

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.847 ^[27]

Method

Logrank

Confidence interval

Notes
[27] - Day 1 to 92: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 4

Comparison groups

Placebo v CAT-354 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.987 ^[28]

Method

Logrank

Confidence interval

Notes
[28] - Day 1 to 169: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 5

Comparison groups

Placebo v CAT-354 300 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.992 ^[29]

Method

Logrank

Confidence interval

Notes
[29] - Day 1 to 169: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Statistical analysis 6

Comparison groups

Placebo v CAT-354 600 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.688 ^[30]

Method

Logrank

Confidence interval

Notes
[30] - Day 1 to 169: P-value was calculated against placebo group from a stratified log-rank test with atopic asthma status and tertile of baseline mean ACQ score as the stratification factors.

Adverse events

Top of page

Timeframe for reporting adverse events

Day 1 to 169

Adverse event reporting additional description

Safety population included all participants who received any dose of the investigational product.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

13.0

Reporting group title

Placebo

Reporting group description

Placebo matched to CAT-354 subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 600 mg

Reporting group description

CAT-354 600 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 300 mg

Reporting group description

CAT-354 300 mg subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Reporting group title

CAT-354 150 mg

Reporting group description

CAT-354 150 milligram (mg) subcutaneous injection once every 2 weeks on Day 1, 15, 29, 43, 57, 71, and 85.

Serious adverse events	Placebo	CAT-354 600 mg	CAT-354 300 mg	CAT-354 150 mg
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 47 (6.38%)	1 / 48 (2.08%)	0 / 51 (0.00%)	2 / 47 (4.26%)
number of deaths (all causes)	1	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardio-respiratory arrest
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Nervous system disorders
Brain injury
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Post cholecystectomy syndrome
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	2 / 47 (4.26%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Somatoform disorder
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Sinusitis
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo	CAT-354 600 mg	CAT-354 300 mg	CAT-354 150 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 47 (36.17%)	25 / 48 (52.08%)	25 / 51 (49.02%)	19 / 47 (40.43%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 47 (0.00%)	2 / 48 (4.17%)	1 / 51 (1.96%)	1 / 47 (2.13%)
occurrences all number	0	2	1	1
Labile hypertension
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Hypertensive crisis
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Influenza like illness
subjects affected / exposed	2 / 47 (4.26%)	3 / 48 (6.25%)	2 / 51 (3.92%)	1 / 47 (2.13%)
occurrences all number	2	4	2	1
Infusion site induration
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Injection site erythema
subjects affected / exposed	1 / 47 (2.13%)	2 / 48 (4.17%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	7	3	1	0
Injection site induration
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Injection site inflammation
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	2	0
Injection site pain
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	2 / 51 (3.92%)	2 / 47 (4.26%)
occurrences all number	0	7	8	3
Injection site pruritus
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	1 / 47 (2.13%)
occurrences all number	0	0	1	1
Injection site rash
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Injection site reaction
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Oedema peripheral
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Pyrexia
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Menopausal disorder
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	0	0	0
Menstruation irregular
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	3 / 47 (6.38%)	6 / 48 (12.50%)	5 / 51 (9.80%)	5 / 47 (10.64%)
occurrences all number	6	9	6	9
Cough
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	1	1	0
Dyspnoea
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Epistaxis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Nasal congestion
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Productive cough
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	2 / 51 (3.92%)	0 / 47 (0.00%)
occurrences all number	0	1	2	0
Rhinitis allergic
subjects affected / exposed	1 / 47 (2.13%)	1 / 48 (2.08%)	1 / 51 (1.96%)	1 / 47 (2.13%)
occurrences all number	1	2	1	4
Rhinorrhoea
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Psychiatric disorders
Acute psychosis
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Nightmare
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	1	0	1
Blood bilirubin
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Blood chloride increased
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Blood glucose increased
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Blood urea increased
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Lymphocyte count decreased
subjects affected / exposed	3 / 47 (6.38%)	1 / 48 (2.08%)	1 / 51 (1.96%)	2 / 47 (4.26%)
occurrences all number	3	1	1	2
Neutrophil count decreased
subjects affected / exposed	3 / 47 (6.38%)	2 / 48 (4.17%)	1 / 51 (1.96%)	3 / 47 (6.38%)
occurrences all number	3	2	2	3
Platelet count decreased
subjects affected / exposed	1 / 47 (2.13%)	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	2	0	0
Reticulocyte count decreased
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Urine analysis abnormal
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
White blood cell count decreased
subjects affected / exposed	1 / 47 (2.13%)	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	1	1	1	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Fall
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Limb injury
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Muscle rupture
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	1 / 51 (1.96%)	2 / 47 (4.26%)
occurrences all number	1	0	1	2
Headache
subjects affected / exposed	2 / 47 (4.26%)	6 / 48 (12.50%)	1 / 51 (1.96%)	6 / 47 (12.77%)
occurrences all number	3	7	1	8
Hypoaesthesia
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	2	0
Intercostal neuralgia
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Lethargy
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Sciatica
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Somnolence
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	5
Blood and lymphatic system disorders
Eosinophilia
subjects affected / exposed	1 / 47 (2.13%)	3 / 48 (6.25%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	1	3	0	1
Leukopenia
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	2	0	0	0
Monocytopenia
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Monocytosis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Neutropenia
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Eye disorders
Conjunctivitis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	2	0	0
Keratitis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	0	0	0
Abdominal pain lower
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Diarrhoea
subjects affected / exposed	0 / 47 (0.00%)	5 / 48 (10.42%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	6	0	0
Gastritis
subjects affected / exposed	1 / 47 (2.13%)	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	2	0	0
Nausea
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	1	0	1
Odynophagia
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Vomiting
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	1	1	0
Biliary dyskinesia
subjects affected / exposed	1 / 47 (2.13%)	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	1	1	1	0
Hyperbilirubinaemia
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Pruritus
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Renal and urinary disorders
Crystalluria
subjects affected / exposed	0 / 47 (0.00%)	3 / 48 (6.25%)	1 / 51 (1.96%)	1 / 47 (2.13%)
occurrences all number	0	3	1	1
Haematuria
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	1	1	0
Leukocyturia
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	1	0	1
Nitrituria
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Urinary tract inflammation
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	1	0	1	0
Back pain
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	1	1	0
Muscle spasms
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Muscle tightness
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	1 / 51 (1.96%)	2 / 47 (4.26%)
occurrences all number	0	1	1	2
Pain in extremity
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	1	0	2	0
Infections and infestations
Acute tonsillitis
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Bacteriuria
subjects affected / exposed	0 / 47 (0.00%)	4 / 48 (8.33%)	2 / 51 (3.92%)	2 / 47 (4.26%)
occurrences all number	0	4	2	2
Bronchitis
subjects affected / exposed	3 / 47 (6.38%)	0 / 48 (0.00%)	1 / 51 (1.96%)	2 / 47 (4.26%)
occurrences all number	3	0	1	2
Escherichia infection
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Gastroenteritis
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
H1n1 influenza
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Influenza
subjects affected / exposed	2 / 47 (4.26%)	1 / 48 (2.08%)	2 / 51 (3.92%)	0 / 47 (0.00%)
occurrences all number	2	1	2	0
Laryngitis
subjects affected / exposed	0 / 47 (0.00%)	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	2	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Nasopharyngitis
subjects affected / exposed	4 / 47 (8.51%)	4 / 48 (8.33%)	3 / 51 (5.88%)	3 / 47 (6.38%)
occurrences all number	4	5	4	5
Otitis media acute
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Pharyngitis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	2 / 51 (3.92%)	2 / 47 (4.26%)
occurrences all number	0	1	2	2
Pharyngitis bacterial
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Respiratory tract infection
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Respiratory tract infection viral
subjects affected / exposed	1 / 47 (2.13%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	1	0	1	0
Rhinitis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	2 / 51 (3.92%)	2 / 47 (4.26%)
occurrences all number	0	1	2	3
Tonsillitis
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Tooth abscess
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Tooth infection
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 47 (0.00%)
occurrences all number	0	0	1	0
Urinary tract infection
subjects affected / exposed	0 / 47 (0.00%)	2 / 48 (4.17%)	1 / 51 (1.96%)	3 / 47 (6.38%)
occurrences all number	0	2	1	3
Urinary tract infection bacterial
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Viral infection
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Vulvovaginitis
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	0	1	0	0
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1
Hyperglycaemia
subjects affected / exposed	0 / 47 (0.00%)	1 / 48 (2.08%)	1 / 51 (1.96%)	1 / 47 (2.13%)
occurrences all number	0	1	1	2
Hypocalcaemia
subjects affected / exposed	1 / 47 (2.13%)	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 47 (0.00%)
occurrences all number	1	1	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 47 (0.00%)	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 47 (2.13%)
occurrences all number	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

12 Mar 2009

- Modified the description of the gene and protein expression analyses to be performed as part of the exploratory analyses. - The upper age limit for participants in the study was increased to 65 years from 55 years - The inclusion criteria was modified: 1. To place an upper limit for predicted prebronchodilator FEV1 value of less than or equal to (<=) ) 80% of individual predicted value at Visits 1 and 3. 2. Provide clarification to ensure that only participants with uncontrolled asthma. 3. Clarified that participants should have an ACQ score >= 1.5 at Visits 1 and 3. 4. Clarified for the requirement for a chest x-ray from the previous 12 months that had no findings suggestive of acute or chronic respiratory pathology other than asthma. - Exclusion criteria was amended: 1. For the modification to exclude participants with a history of ingestion of untreated water in a location known to be infected with parasites, resulting in acute or chronic diarrhea; or a diagnosis of parasitic infection within 6 months prior to screening rather than 1 month prior to randomization as previously stated. 2. To change from a history of primary immunodeficiency to a history of any known immunodeficiency disorder. 3. Addition of positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or participant’s verbal report, A positive human immunodeficiency virus test or is taking antiretroviral medications, as determined by medical history and/or participant’s verbal report. - Protocol was revised to specify that the SC injections of investigational product were to be administered into the SC tissue of the anterior thigh rather than the triceps muscle as previously written. - Gamma-glutamyl transferase was added to the serum chemistry panel. -Definition of asthma exacerbation and resolution of asthma exacerbation was modified. - Text stating that acute exacerbations were to be reported separately was been deleted from the protocol.

18 Nov 2009

Modified the description of the gene and protein expression analyses to be performed as part of the exploratory analyses. - The inclusion criteria was modified: 1. To remove the upper limit on the prebronchodilator FEV1 value of greater than or equal to (>=) 40 % and <= 80% of individual predicted value at Visits 1 and 3. 2. To increase the upper limit of body mass index (BMI) 35 to 40 kilogram per meter square (kg/m^2). 3. The use of a condom by a male sexual partner of a female subject of childbearing potential was added to the list of acceptable methods of contraception. - Additional criteria for allowing one repeat screening visit was added to the protocol. - The requirements to withhold agents prior to spirometry were clarified to be consistent with the recommendations of the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. - The text describing visits for participants who prematurely discontinue the study was clarified. - The language describing blinding and the planned Stage 1 analysis was clarified to make it clear that group level unblinded data from the Stage 1 analysis would not be shared outside the sponsor.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92

Primary: Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92

Secondary: Time to First Observed Asthma Control

Secondary: Time to First Observed Asthma Control

Secondary: Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites at Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169

Secondary: Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) Recorded at Study Sites at Day 1, 15, 29, 43, 57, 71, 85, 92, 127 and 169

Secondary: Change From Baseline in Peak Expiratory Flow (PEF) Recorded at Home Every Week From Day 1 to 169

Secondary: Change From Baseline in Peak Expiratory Flow (PEF) Recorded at Home Every Week From Day 1 to 169

Secondary: Number of Puffs of Rescue Beta-2 Agonist Per Week

Secondary: Number of Puffs of Rescue Beta-2 Agonist Per Week

Secondary: Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores

Secondary: Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores

Secondary: Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores at Day 29, 57, 92, 127 and 169

Secondary: Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Scores at Day 29, 57, 92, 127 and 169

Secondary: Patient Global Impression of Change (PGIC)

Secondary: Patient Global Impression of Change (PGIC)

Secondary: Percentage of Participants with Mean Asthma Control Questionnaire (ACQ) Score Less Than or Equal to 0.75 or ACQ Score Greater Than 0.75 but Less Than 1.5

Secondary: Percentage of Participants with Mean Asthma Control Questionnaire (ACQ) Score Less Than or Equal to 0.75 or ACQ Score Greater Than 0.75 but Less Than 1.5

Secondary: Serum Concentration for CAT-354

Secondary: Serum Concentration for CAT-354

Secondary: Number of Participants With Anti-Drug Antibodies to CAT-354 at any Visit

Secondary: Number of Participants With Anti-Drug Antibodies to CAT-354 at any Visit

Secondary: Percentage of Participants With Positive Serum Antibodies to CAT-354 at any Visit

Secondary: Percentage of Participants With Positive Serum Antibodies to CAT-354 at any Visit

Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Secondary: Percentage of Participants With at least 1 Moderate or Severe Exacerbation

Secondary: Percentage of Participants With at least 1 Moderate or Severe Exacerbation

Secondary: Moderate or Severe Asthma Exacerbations per Person per Annum

Secondary: Moderate or Severe Asthma Exacerbations per Person per Annum

Secondary: Time to First Moderate or Severe Asthma Exacerbation

Secondary: Time to First Moderate or Severe Asthma Exacerbation

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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