A Study to Assess the Efficacy, Safety, and Tolerability of CAT-354 in Subjects With Asthma

Study identifier:CAT-354-0603

ClinicalTrials.gov identifier:NCT00640016

EudraCT identifier:2007-002090-31

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of CAT-354

Medical condition

asthma

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 01 Jan 2008

Primary Completion Date: 01 Jul 2008

Study Completion Date: 01 Jul 2008

Study design

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

Verification:

Verified 01 Dec 2016 by MedImmune, LLC

Collaborators

Cambridge Antibody Technology, PRA International

Inclusion and exclusion criteria

Inclusion Criteria

- Signed and dated written informed consent is obtained prior to any study related procedure taking place
- Women either infertile (example [e.g.], hysterectomized, sterile or post-menopausal with amenorrhea of least 1 year duration) or who are practicing an acceptable form of birth control
- Uncontrolled (refractory) asthma despite treatment with a minimum dose of 800 microgram (mcg) beclomethasonedipropionate or equivalent inhaled corticosteroid per day plus 1 or more additional controller, that is, long-acting beta-agonist, leukotriene antagonist or theophylline. Oral corticosteroids (not parenteral) as additional treatment at any dose are acceptable
- A forced expiratory volume in 1 second (FEV1) acceptable for airway hyper-responsiveness (AHR) challenge tests (greater than 60 percent of predicted normal) on the challenge days
- A provocative concentration of methacholine causing a 20 percent fall in FEV1 (PC20) less than 4 milligram per milliliter (mg/mL)
- Aged 18-80 years
- A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities
- Clinical chemistry, hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
- Body weight of less than 130 kilogram (kg)
- No other clinically significant abnormality on history and clinical examination
- Able to comply with the requirements of the protocol.

Exclusion Criteria

- Experienced a severe exacerbation within 28 days preceding Day -28/-14 to Day 0
- Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0
- Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study
- Participation in another study within 5 half-lives or 3 months of the start of this study, whichever is the longer
- Lower respiratory tract infection within 6 weeks of Day -28/-14 to Day 0
- Current smokers or ex-smokers with greater than 10 pack-years
- Blood donation (more than 550 mL) in the previous 2 months
- Excessive intake of alcohol (as judged by the Investigator) or evidence of drug or solvent abuse
- Subjects with a physician-diagnosis of any other significant lung disease, including a primary diagnosis of chronic obstructive pulmonary disease or bronchiectasis, or lung cancer, sarcoidosis, tuberculosis, pulmonary fibrosis and cystic fibrosis
- Concurrent medication from Day -28/-14 to Day 0 (Screening visit) and for the duration of the study with any of the prohibited medications
- Significant, uncontrolled disease including serious psychological disorders, chronic renal failure, uncontrolled hypertension
- systolic blood pressure greater than 200 millimeters of mercury (mmHg), or diastolic blood pressure greater than 100 mmHg, heart disease, psoriasis requiring treatment and subjects who have had a heart attack or stroke within the 3 months preceding Day -28/-14 to Day 0, or who have a known aneurysm
- Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0
- Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study
- Any factor which, in the opinion of the Investigator, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol (that is, inability to complete study diary, perform peak expiratory flow (PEF) measurements)
- The subject's primary care physician recommends the subject should not take part in the study
- Known hypersensitivity to CAT-354 or its components, to the challenge agents used in the study or to related drugs.

No locations available

Arms	Assigned Interventions
Placebo Comparator: Placebo Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.	Other: Placebo Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56. Other Name: Tralokinumab
Experimental: CAT-354 1 mg/kg CAT-354 1 milligram per kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Biological/Vaccine: CAT-354 1 mg/kg CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56. Other Name: Tralokinumab
Experimental: CAT-354 5 mg/kg CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Biological/Vaccine: CAT-354 5 mg/kg CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56. Other Name: Tralokinumab
Experimental: CAT-354 10 mg/kg CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56	Other: CAT-354 10 mg/kg CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Placebo	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Participant Flow: Overall Study

	Placebo	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
STARTED	3	3	4	4
Treated	3	2	4	4
COMPLETED	1	1	1	1
NOT COMPLETED	2	2	3	3
Withdrawal by Subject	0	1	0	0
Study termination	2	1	3	2
Adverse Event	0	0	0	1

Baseline Characteristics

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

Analysis population included all participants who were enrolled.

Reporting Groups

	Description
Placebo	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Baseline Measures

	Placebo	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg	Total
Number of Participants [units: Participants]	3	3	4	4	14
Age Continuous [units: years] Mean ± Standard Deviation	34.00 ± 11.136	34.00 ± 14.933	37.75 ± 9.878	40.75 ± 15.086	37.00 ± 11.708
Gender, Male/Female [units: participants]
Female	3	3	2	3	11
Male	0	0	2	1	3

Outcome Measures

1. Primary Outcome Measure: Change From Baseline in Doubling Concentration of Methacholine at Day 28 [ Time Frame: Baseline and Day 28 ]

Measure Type	Primary
Measure Name	Change From Baseline in Doubling Concentration of Methacholine at Day 28
Measure Description	Change in doubling concentrations of methacholine was calculated as Log2 PC20 (Visit x) - Log2 PC20 (Baseline), where x was the post-baseline assessment (Day 28) and PC20 was provocative concentration of methacholine causing 20 percent fall in forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Change in doubling concentration was summarized for sub-therapeutic dose (placebo and CAT-354 1 milligram/kilogram [mg/kg]) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time Frame	Baseline and Day 28
Safety Issue?	No

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.
Safety population included all participants who received at least 1 dose of study medication. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	8	5
Change From Baseline in Doubling Concentration of Methacholine at Day 28 [units: log2 milligram/deciliter (mg/dL)] Mean (Standard Deviation)
Baseline (n=8, 5)	-0.604 (2.4080)	-1.545 (0.8952)
Change at Day 28 (n=5, 4)	-0.207 ( 1.0450)	0.125 ( 2.3433)

No statistical analysis provided for Change From Baseline in Doubling Concentration of Methacholine at Day 28

2. Secondary Outcome Measure: Change From Baseline in Doubling concentration of Methacholine at Day 56, 84 or Early Termination [ Time Frame: Baseline, Day 56, 84 or early termination (any time before Day 84) ]

Measure Type	Secondary
Measure Name	Change From Baseline in Doubling concentration of Methacholine at Day 56, 84 or Early Termination
Measure Description	Change in doubling concentrations of methacholine was calculated as Log2 PC20 (Visit x) - Log2 PC20 (Baseline), where x was the post-baseline assessment (Day 28) and PC20 was provocative concentration of methacholine causing 20 percent fall in forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Change in doubling concentration was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time Frame	Baseline, Day 56, 84 or early termination (any time before Day 84)
Safety Issue?	No

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.
Safety population included all participants who received at least 1 dose of study medication. Here, ‘N’ (number of participants analyzed) signifies those participants who were evaluable for this measure, and 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	3	2
Change From Baseline in Doubling concentration of Methacholine at Day 56, 84 or Early Termination [units: log2 mg/dL] Mean (Standard Deviation)
Change at Day 56 (n=2, 2)	0.062 (1.1309)	-1.423 (0.4059)
Change at Day 84 (n=2, 2)	-0.038 (0.1410)	-1.846 (0.0431)
Change at Early termination (n=3, 2)	-0.514 (0.8636)	0.417 (0.9840)

No statistical analysis provided for Change From Baseline in Doubling concentration of Methacholine at Day 56, 84 or Early Termination

3. Secondary Outcome Measure: Forced expiratory volume in 1 second (FEV1) [ Time Frame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84) ]

Measure Type	Secondary
Measure Name	Forced expiratory volume in 1 second (FEV1)
Measure Description	The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time Frame	Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84)
Safety Issue?	No

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.
Safety population included all participants who received at least 1 dose of study medication. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	8	5
Forced expiratory volume in 1 second (FEV1) [units: liters] Mean (Standard Deviation)
Day 0: Predose (n=8, 5)	2.718 (0.5458 )	2.640 (0.3994)
Day 0: 30 minutes postdose (n=8, 5)	2.684 (0.5695)	2.624 (0.4126)
Day 0: 6 hours postdose (n=8, 5)	2.606 (0.5731)	2.550 (0.4304)
Day 4 (n=8, 5)	2.814 (0.6048)	2.606 (0.2919)
Day 14 (n=6, 5)	2.323 (0.5703)	2.520 (0.0812)
Day 28: Predose (n=5, 4)	2.598 (0.4676 )	2.850 (0.2082)
Day 28: 30 minutes postdose (n=4, 4)	2.535 (0.5639)	2.918 (0.2822)
Day 28: 6 hours postdose (n=4, 4)	2.400 (0.5254 )	2.665 (0.2748)
Day 35 (n= 4, 4)	2.260 (0.5464)	2.778 (0.4228)
Day 56: Predose (n=2, 2)	2.555 (0.6718)	2.700 (0.3677)
Day 56: 30 minutes postdose (n=2, 2)	2.705 (0.7990)	2.830 (0.1697)
Day 56: 6 hours postdose (n=2, 2)	2.510 (0.7071)	2.690 (0.2404)
Day 63 (n= 2, 2)	2.505 (0.6859)	2.580 (0.0283)
Day 84: (n=2, 2)	2.680 ( 0.7778 )	2.540 (0.4101)
Early Termination (n=4, 3)	3.018 (0.5803)	2.867 (0.4400)

No statistical analysis provided for Forced expiratory volume in 1 second (FEV1)

4. Secondary Outcome Measure: Forced Vital Capacity (FVC) [ Time Frame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84) ]

Measure Type	Secondary
Measure Name	Forced Vital Capacity (FVC)
Measure Description	The FVC was volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time Frame	Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84)
Safety Issue?	No

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.
Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	8	5
Forced Vital Capacity (FVC) [units: liters] Mean (Standard Deviation)
Day 0: Predose (n= 8, 5)	3.828 (0.8215 )	3.666 (0.6068)
Day 0: 30 minutes postdose (n= 8, 5)	3.823 (0.6500)	3.722 (0.6752)
Day 0: 6 hours postdose (n= 8, 5)	3.808 (0.7718 )	3.722 (0.7297)
Day 4 (n= 8, 5)	3.988 (0.6058)	3.824 (0.7415)
Day 14 (n=6, 5)	3.462 (0.5926 )	3.710 (0.5220)
Day 28: Predose (n=5, 4)	3.908 (0.7670 )	3.883 (0.6412)
Day 28: 30 minutes postdose (n=4, 4)	3.878 (0.7876)	3.980 (0.7951)
Day 28: 6 hours postdose (n=4, 4)	3.810 (0.7409)	3.790 (0.4830)
Day 35 (n=4, 4)	3.613 (0.6874)	3.920 (0.7777)
Day 56: Predose (n=2, 2)	3.700 (0.5233)	3.410 (0.3818)
Day 56: 30 minutes postdose (n=2, 2)	3.775 (0.5303)	3.540 (0.4667)
Day 56: 6 hours postdose (n=2, 2)	3.715 (0.6435)	3.545 (0.3748)
Day 63 (n=2, 2)	3.705 (0.5162 )	3.575 (0.5020)
Day 84: (n=2, 2)	3.710 (0.6505)	3.415 (0.3323)
Early Termination (n=4, 3)	3.908 (0.8070)	4.193 (0.8364)

No statistical analysis provided for Forced Vital Capacity (FVC)

5. Secondary Outcome Measure: Forced Expiratory Volume in 1 second (FEV1) as Percentage of Forced Vital Capacity (FVC) [ Time Frame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, Day 63, 84 or early termination (any time before Day 84) ]

Measure Type	Secondary
Measure Name	Forced Expiratory Volume in 1 second (FEV1) as Percentage of Forced Vital Capacity (FVC)
Measure Description	Percentage of FEV1 was calculated as (FEV1/FVC)*100. It signified the percentage of the total amount of air exhaled from the lungs during the first second of forced exhalation. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Result was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time Frame	Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, Day 63, 84 or early termination (any time before Day 84)
Safety Issue?	No

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.
Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	8	5
Forced Expiratory Volume in 1 second (FEV1) as Percentage of Forced Vital Capacity (FVC) [units: percentage of FVC] Mean (Standard Deviation)
Day 0: Predose (n=8, 5)	71.875 (10.3156 )	72.600 (11.4149)
Day 0: 30 minutes postdose (n=8, 5)	70.250 (9.1613 )	71.600 (13.1833)
Day 0: 6 hours postdose (n=8, 5)	69.125 (12.5178)	69.600 (12.1984)
Day 4 (n=8, 5)	71.000 (13.1909)	69.400 (8.7063)
Day 14 (n=6, 5)	66.667 (7.5011 )	68.800 (8.1670)
Day 28: Predose (n=5, 4)	67.400 (13.1263)	74.500 (11.2694)
Day 28: 30 minutes postdose (n=4, 4)	66.500 (13.9881)	74.500 (9.6782)
Day 28: 6 hours postdose (n=4, 4)	63.750 (12.3390)	71.250 (13.8173)
Day 35 (n=4, 4)	62.500 (7.5498)	71.750 (7.8049)
Day 56: Predose (n=2, 2)	68.000 (8.4853)	80.000 (19.7990)
Day 56: 30 minutes postdose (n=2, 2)	71.000 (11.3137)	81.000 (15.5563)
Day 56: 6 hours postdose (n=2, 2)	67.000 (7.0711)	76.500 (14.8492)
Day 63 (n=2, 2)	66.500 (9.1924 )	72.500 (9.1924)
Day 84 (n=2, 2)	71.500 (9.1924)	75.500 (19.0919)
Early Termination (n=4, 3)	77.750 (9.8107)	69.000 (5.5678)

No statistical analysis provided for Forced Expiratory Volume in 1 second (FEV1) as Percentage of Forced Vital Capacity (FVC)

6. Secondary Outcome Measure: Asthma Control Questionnaire (ACQ) Total Score [ Time Frame: Baseline, Day 28, 56, 84 or early termination (any time before Day 84) ]

Measure Type	Secondary
Measure Name	Asthma Control Questionnaire (ACQ) Total Score
Measure Description	The ACQ is questionnaire that comprises of 7-questions evaluating participant’s asthma control. Six self-administered questions assess asthma control over the past week covering nocturnal waking, morning symptoms, activity limitations, shortness of breath, wheezing, and short-acting bronchodilator use; using 7-point ordinal rating scale from 0 (good control) to 6 (poor control). Seventh question is completed by a health professional on forced expiratory volume in 1 second (FEV1) percentage (%) predicted; scale: 0 (greater than [>] 95% predicted) to 6 (less than [<] 50% predicted. Final score is the average score of the 7 questions, with a score range of 0 (well controlled) to 6 (extremely poor controlled). Result was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time Frame	Baseline, Day 28, 56, 84 or early termination (any time before Day 84)
Safety Issue?	No

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.
Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	8	5
Asthma Control Questionnaire (ACQ) Total Score [units: units on a scale] Mean (Standard Deviation)
Baseline (n=8, 5)	2.44 (0.737 )	1.77 (0.861)
Day 28 (n=5, 4)	2.00 (0.416)	1.46 (0.914)
Day 56 (n=2, 2)	1.43 (0.808)	1.50 (1.111)
Day 84 (n=2, 2)	1.57 (1.010)	2.36 (0.101)
Early Termination (n=5, 3)	1.72 (1.304)	0.57 (0.378)

No statistical analysis provided for Asthma Control Questionnaire (ACQ) Total Score

7. Secondary Outcome Measure: Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Day 0 to 84 ]

Measure Type	Secondary
Measure Name	Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Measure Description	The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.
Time Frame	Day 0 to 84
Safety Issue?	No

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.
Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	0	0
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [units: liters] Mean (Standard Deviation)

No statistical analysis provided for Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)

8. Secondary Outcome Measure: Number of Participants With Diary Data [ Time Frame: Day 0, 4, 14, 28, 35, 56, 63 to Day and 84 ]

Measure Type	Secondary
Measure Name	Number of Participants With Diary Data
Measure Description	Participants recorded asthma symptoms, use of reliever inhalers (beta-agonist use for symptom relief and as prophylaxis), and morning and evening peak expiratory flow (PEF) measurements in a diary.
Time Frame	Day 0, 4, 14, 28, 35, 56, 63 to Day and 84
Safety Issue?	No

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.
Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	0	0
Number of Participants With Diary Data [units: participants]

No statistical analysis provided for Number of Participants With Diary Data

9. Secondary Outcome Measure: Number of Participants With Exacerbations [ Time Frame: Day 0 to Day 84 ]

Measure Type	Secondary
Measure Name	Number of Participants With Exacerbations
Measure Description	Exacerbation was defined as: Mild (determined from diary data) - 2 consecutive days satisfying the same or 1 of the following criteria: any night with awakening(s) due to asthma or morning PEF 20 % or more below baseline where baseline = average of the 10 days before randomization or as-needed medication use of 2 inhalations or more in 24 hours above baseline where baseline = average of the 10 days before randomization. Severe (determined by taking an exacerbation update and history): deterioration of asthma resulting in emergency treatment or hospitalization or need for oral steroids for 3 days or more (as judged by the Investigator).
Time Frame	Day 0 to Day 84
Safety Issue?	No

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.
Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	0	0
Number of Participants With Exacerbations [units: participants]

No statistical analysis provided for Number of Participants With Exacerbations

10. Secondary Outcome Measure: Morning Peak Flow and Peak Flow Variability [ Time Frame: Day 0 to Day 84 ]

Measure Type	Secondary
Measure Name	Morning Peak Flow and Peak Flow Variability
Measure Description	Peak flow is a participant’s maximum speed of expiration.
Time Frame	Day 0 to Day 84
Safety Issue?	No

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.
Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	0	0
Morning Peak Flow and Peak Flow Variability [units: liters/minute] Mean (Standard Deviation)

No statistical analysis provided for Morning Peak Flow and Peak Flow Variability

11. Secondary Outcome Measure: Adult Asthma Quality of Life (QoL) Questionnaire Final Score [ Time Frame: Day 0, 28, 84 or early termination (any time before Day 84) ]

Measure Type	Secondary
Measure Name	Adult Asthma Quality of Life (QoL) Questionnaire Final Score
Measure Description	The AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants are 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 is calculated as the mean response to all questions. The 4 domain scores are 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).
Time Frame	Day 0, 28, 84 or early termination (any time before Day 84)
Safety Issue?	No

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.
Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.

Reporting Groups

	Description
Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (placebo or CAT-354 1mg/kg)
Number of Participants Analyzed [units:participants]	0	0
Adult Asthma Quality of Life (QoL) Questionnaire Final Score [units: units on a scale] Mean (Standard Deviation)

No statistical analysis provided for Adult Asthma Quality of Life (QoL) Questionnaire Final Score

12. Secondary Outcome Measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 [ Time Frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 ]

Measure Type	Secondary
Measure Name	Maximum Observed Serum Concentration (Cmax) for CAT-354
Measure Description
Time Frame	Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Safety Issue?	No

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.
Pharmacokinetic (PK) population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Number of Participants Analyzed [units:participants]	1	1	1
Maximum Observed Serum Concentration (Cmax) for CAT-354 [units: microgram/milliliter (mcg/mL)] Mean (Standard Deviation)
After first dose (Day 0)	27.7 (NA)^[1]	219 (NA)^[2]	163 (NA)^[3]
After second dose (Day 28)	34.5 (NA)^[4]	255 (NA)^[5]	235 (NA)^[6]
After third dose (Day 56)	33.4 (NA)^[7]	338 (NA)^[8]	251 (NA)^[9]

No statistical analysis provided for Maximum Observed Serum Concentration (Cmax) for CAT-354

13. Secondary Outcome Measure: Minimum Observed Serum Concentration (Cmin) for CAT-354 [ Time Frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 ]

Measure Type	Secondary
Measure Name	Minimum Observed Serum Concentration (Cmin) for CAT-354
Measure Description
Time Frame	Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Safety Issue?	No

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.
PK population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Number of Participants Analyzed [units:participants]	1	1	1
Minimum Observed Serum Concentration (Cmin) for CAT-354 [units: mcg/mL] Mean (Standard Deviation)
After first dose (Day 0)	4.84 (NA)^[1]	51.8 (NA)^[2]	52.8 (NA)^[3]
After second dose (Day 28)	7.91 (NA)^[4]	54.1 (NA)^[5]	64.4 (NA)^[6]
After third dose (Day 56)	9.70 (NA)^[7]	85.5 (NA)^[8]	68.4 (NA)^[9]

No statistical analysis provided for Minimum Observed Serum Concentration (Cmin) for CAT-354

14. Secondary Outcome Measure: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 [ Time Frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354
Measure Description
Time Frame	Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Safety Issue?	No

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.
PK population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Number of Participants Analyzed [units:participants]	1	1	1
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 [units: microgramday/milliliter (mcgday/mL)] Mean (Standard Deviation)
After first dose (Day 0)	335 (NA)^[1]	2820 (NA)^[2]	2090 (NA)^[3]
After second dose (Day 28)	408 (NA)^[4]	4720 (NA)^[5]	3080 (NA)^[6]
After third dose (Day 56)	499 (NA)^[7]	3690 (NA)^[8]	3420 (NA)^[9]

No statistical analysis provided for Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354

15. Secondary Outcome Measure: Accumulation Ratio for CAT-354 (RA) [ Time Frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 ]

Measure Type	Secondary
Measure Name	Accumulation Ratio for CAT-354 (RA)
Measure Description	Accumulation ratio (RA) is calculated for Cmax, Cmin and AUC as RA for Cmax = Cmax (56 - 84)/Cmax (0 - 28); Similarily, RA for Cmin = Cmin (56 - 84)/Cmin (0 - 28) and RA for AUC= AUC (56 - 84)/AUC (0 - 28) where Cmax (0 - 28) and Cmax (56 - 84) are the maximum observed serum concentration after first dose (Day 0 to Day 28) and after third dose (Day 56 to Day 84), respectively; Cmin (0 - 28) and Cmin (56 - 84) are the minimum observed serum concentration after first and third dose, respectively; AUC (0 - 28) and AUC (56 - 84) are the area under the serum concentration time curve over a dosage interval determined after first and third dose, respectively.
Time Frame	Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Safety Issue?	No

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.
PK population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Number of Participants Analyzed [units:participants]	1	1	1
Accumulation Ratio for CAT-354 (RA) [units: ratio] Mean (Standard Deviation)
RA for Cmin	1.20 (NA)^[1]	1.54 (NA)^[2]	1.73 (NA)^[3]
RA for Cmax	2.00 (NA)^[4]	1.65 (NA)^[5]	1.30 (NA)^[6]
RA for AUC	1.49 (NA)^[7]	1.31 (NA)^[8]	1.64 (NA)^[9]

No statistical analysis provided for Accumulation Ratio for CAT-354 (RA)

16. Secondary Outcome Measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 0 to 84 ]

Measure Type	Secondary
Measure Name	Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 are events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Day 0 to 84
Safety Issue?	Yes

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.
Safety population included all participants who received at least 1 dose of study medication.

Reporting Groups

	Description
Placebo	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 1 mg/kg	CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Measured Values

	Placebo	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Number of Participants Analyzed [units:participants]	3	2	4	4
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [units: participants]
TEAEs	2	2	4	3
TESAEs	0	0	0	1

No statistical analysis provided for Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Serious Adverse Events

Time Frame	Day 0 to 84
Additional Description	No text entered.

Reporting Groups

	Description
Placebo	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Serious Adverse Events

Placebo

CAT-354 1 mg/kg

CAT-354 5 mg/kg

CAT-354 10 mg/kg

Total, serious adverse events

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

Immune system disorders

Hypersensitivity¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA. 9.0

Other Adverse Events

Time Frame	Day 0 to 84
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Placebo	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.

Other Adverse Events

Placebo

CAT-354 1 mg/kg

CAT-354 5 mg/kg

CAT-354 10 mg/kg

Total, other (not including serious) adverse events

# participants affected / at risk

2/3 (66.67%)

2/2 (100.00%)

4/4 (100.00%)

2/4 (50.00%)

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

# events

General disorders and administration site conditions

Chest discomfort¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

# events

General disorders and administration site conditions

Inflammation¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

0/4 (0.00%)

1/4 (25.00%)

# events

Immune system disorders

Seasonal allergy¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

0/4 (0.00%)

2/4 (50.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

2/3 (66.67%)

2/2 (100.00%)

1/4 (25.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/3 (33.33%)

0/2 (0.00%)

0/4 (0.00%)

# events

Investigations

Forced expiratory volume decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/2 (50.00%)

0/4 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

1/3 (33.33%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹,^†

# participants affected / at risk

0/3 (0.00%)

1/2 (50.00%)

0/4 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

0/3 (0.00%)

0/2 (0.00%)

1/4 (25.00%)

0/4 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA. 9.0

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: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The Principal Investigator (PIs) also agree for data to be presented first as a joint, multi-center publication.

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
Study was prematurely terminated due to low recruitment rate, delay due to temporary halt and potential for expiry date of study drug. It was not considered possible to draw meaningful conclusions from the small dataset.