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

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00640016
• Collaborator: Cambridge Antibody Technology (Other), PRA Health Sciences (Industry)
• Enrollment: 14
• Locations: 41
• Arms: 4
• Duration (Months): 6
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To investigate the effects of CAT-354 on airway hyper-responsiveness (AHR) in uncontrolled asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Other: Placebo; Biological: CAT-354 1 mg/kg; Biological: CAT-354 5 mg/kg; Other: CAT-354 10 mg/kg	Phase 2

Detailed Description

This is a randomized, stratified, double-blind, placebo-controlled, multicenter, multinational study in subjects with uncontrolled asthma despite optimal treatment. Following confirmation of eligibility, subjects will be randomly assigned on Day 0, to 1 of 4 dose groups 1 mg/kg CAT-354, 5 mg/kg CAT-354, 10 mg/kg CAT or Placebo to match all doses of CAT-354. Doses of the assigned treatment will be administered on three occasions 28 days apart. Subjects will be assessed for efficacy, including airway hyper-responsiveness (AHR), safety, pharmacokinetic, pharmacodynamics and immunogenicity until Day 84 post-first dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of CAT-354
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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: 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 Names: 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: 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 Names: 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.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Doubling Concentration of Methacholine at Day 28 [Baseline and Day 28]

   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.

Secondary Outcome Measures

1. Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination [Baseline, Day 56, 84 or early termination (any time before Day 84)]

   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.

2. Forced Expiratory Volume in 1 Second (FEV1) [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)]

   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.

3. Forced Vital Capacity (FVC) [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)]

   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.

4. Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) [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)]

   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.

5. Asthma Control Questionnaire (ACQ) Total Score [Baseline, Day 28, 56, 84 or early termination (any time before Day 84)]

   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.

6. Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [Day 0 to 84]

   The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

7. Number of Participants With Diary Data [Day 0, 4, 14, 28, 35, 56, 63 to Day and 84]

   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.

8. Number of Participants With Exacerbations [Day 0 to Day 84]

   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).

9. Morning Peak Flow and Peak Flow Variability [Day 0 to Day 84]

   Peak flow is a participant's maximum speed of expiration.

10. Adult Asthma Quality of Life (QoL) Questionnaire Final Score [Day 0, 28, 84 or early termination (any time before Day 84)]

    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).

11. Maximum Observed Serum Concentration (Cmax) for CAT-354 [Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56]

12. Minimum Observed Serum Concentration (Cmin) for CAT-354 [Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56]

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

14. Accumulation Ratio for CAT-354 (RA) [Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56]

    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.

15. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [Day 0 to 84]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Vincents Hospital, Thoracic Medicine Unit	Darlinghurst	New South Wales	Australia	2010
2	Respiratory Medicine Department, Mater Adult Hospital,	South Brisbane	Queensland	Australia	4101
3	Princess Alexandria Hospital, Dept of Respiratory Medicine	Woolloongabba	Queensland	Australia	4102
4	Eastern Clinical Research Unit	Box Hill	Victoria	Australia	3128
5	Monash Medical Centre, Dept Respiratory Medicine.	Clayton	Victoria	Australia	3168
6	Dep of Respiratory & Sleep Medicine, Western Hospital	Footscray	Victoria	Australia	3011
7	Respiratory & Sleep Medicine, Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
8	Lung Institute WA, Sir Charles Gardner Hospital	Nedlands	Western Australia	Australia	6009
9	WA Lung Research, Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
10	Evangelische Lungenklinik Berlin - Kardiologie/Pneumologie - 1.OG, Haus 23	Berlin		Germany	13125
11	Med. Klinik m. S. Infektiologie und Pneumologie, Charite - Universitätsmedizin Berlin	Berlin		Germany	D-13353
12	Lungen und Bronchialheikunde	Bonn		Germany	53123
13	Praxis für Lungen-und Bronchialheilkunde, Allergologie und Umweltmedizin	Bonn		Germany	53123
14	Rheinische Friedrich-Wilhelms-Universität, Medizinische Klinik und Poliklinik II, Innere Medizin	Bonn		Germany	53127
15	Internistisches Facharztzentrum Stresemannallee	Frankfurt		Germany	60596
16	Universitätsklinikum Magdeburg Fachbereich Pneumologie	Magdeburg		Germany	39120
17	Universitätsklinikum Mainz, Klinische Forschung Pneumologie, III. med. Klinik	Mainz		Germany	55131
18	Universitätsklinikum Münster Klinik und Poliklinik für Dermatologie	Munster		Germany	48149
19	Universität Rostock, Medizinische Fakultät Klinik und Poliklinik für Innere Medizin	Rostock		Germany	18057
20	Johanniter-Krankenhaus im Fläming gGmbH, Pneumologie	Treuenbrietzen		Germany	14929
21	Academisch Medisch Centrum	Amsterdam		Netherlands	1105 AZ
22	Prywatny Gabinet Internistyczno-Alergologiczny	Bialystok		Poland	15-025
23	ISPL Centrum Medyczne	Białystok		Poland	15-003
24	Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej Akademii Medycznej, Klinika Pneumologii	Katowice		Poland	40-752
25	Niepubliczny Zakład Opieki Zdrowotnej Atopia	Kraków		Poland	31-159
26	Szpital ZOZ Lubin Oddzial Alergologiczny i Chorob Wewnetrznych	Lubin		Poland	59-300
27	Wojewodzki Szpital Specjalistyczny, Poradnia Alergologiczna	Lublin		Poland	20-093
28	Alergopneuma Przychodnia Alergologiczno-Pulmonologiczna Marek Michnar i wsp.	Lublin		Poland	20-607
29	Instytut Gruzlicy i Chorob Pluc	Warszawa		Poland	01-138
30	Wojewódzki Szpital Specjalistyczny w Zgierzu	Zgierz		Poland	95-100
31	Uniwersytecki Szpital Kliniczny nr 1 Im. Norberta Barlickiego w Łodzi	Łódź		Poland	91-153
32	Belfast City Hospital	Belfast		United Kingdom	BT9 7AB
33	Birmingham Heartlands Hospital	Birmingham		United Kingdom	B9 5SS
34	Gartnavel General Hospital	Glasgow		United Kingdom	G12 OYN
35	University Hospitals of Leicester NHS Trust, Glenfield Hospital	Leicester		United Kingdom	LE3 9QP
36	Royal Brompton Hospital	London		United Kingdom	SW3 6HP
37	University Hospital of South Manchester NHS Foundation Trust	Manchester		United Kingdom	M23 9LT
38	Royal Victoria Infirmary	Newcastle upon Tyne		United Kingdom	NE1 4LP
39	Royal Gwent Hospital	Newport		United Kingdom	NP20 2UB
40	Norfolk and Norwich University Hospital	Norwich		United Kingdom	NR4 7UY
41	Lister Hospital	Stevenage, Hertfordshire		United Kingdom	SG1 4AB

Sponsors and Collaborators

• MedImmune LLC
• Cambridge Antibody Technology
• PRA Health Sciences

Investigators

• Study Director: Thomas Mayer, M.D., PRA Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT00640016
• Other Study ID Numbers: CAT-354-0603; 2007-002090-31
• First Posted: Mar 20, 2008
• Last Update Posted: Jan 31, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by MedImmune LLC: Asthma; CAT-354; Tralokinumab
• Additional relevant MeSH terms: Asthma; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Placebo	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Arm/Group Description	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.	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 of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Period Title: Overall Study
STARTED	3	3	4	4
Treated	3	2	4	4
COMPLETED	1	1	1	1
NOT COMPLETED	2	2	3	3

Baseline Characteristics

Arm/Group Title	Placebo	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg	Total
Arm/Group Description	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.	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 of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Total of all reporting groups
Overall Participants	3	3	4	4	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.00 (11.136)	34.00 (14.933)	37.75 (9.878)	40.75 (15.086)	37.00 (11.708)
Gender (Count of Participants)
Female	3 100%	3 100%	2 50%	3 75%	11 78.6%
Male	0 0%	0 0%	2 50%	1 25%	3 21.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Doubling Concentration of Methacholine at Day 28
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg)
Arm/Group Description	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	8	5
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)

2. Secondary Outcome

Title	Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg)
Arm/Group Description	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	3	2
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)

3. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1)
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg)
Arm/Group Description	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	8	5
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)

4. Secondary Outcome

Title	Forced Vital Capacity (FVC)
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg)
Arm/Group Description	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	8	5
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)

5. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC)
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg)
Arm/Group Description	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	8	5
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)

6. Secondary Outcome

Title	Asthma Control Questionnaire (ACQ) Total Score
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg)	Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg)
Arm/Group Description	CAT-354 5 mg/kg or 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	Placebo or CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	8	5
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)

7. Secondary Outcome

Title	Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
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

Outcome Measure Data

Analysis Population Description

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.

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

8. Secondary Outcome

Title	Number of Participants With Diary Data
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

Outcome Measure Data

Analysis Population Description

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.

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

9. Secondary Outcome

Title	Number of Participants With Exacerbations
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

Outcome Measure Data

Analysis Population Description

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.

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

10. Secondary Outcome

Title	Morning Peak Flow and Peak Flow Variability
Description	Peak flow is a participant's maximum speed of expiration.
Time Frame	Day 0 to Day 84

Outcome Measure Data

Analysis Population Description

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.

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

11. Secondary Outcome

Title	Adult Asthma Quality of Life (QoL) Questionnaire Final Score
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)

Outcome Measure Data

Analysis Population Description

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.

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

12. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Arm/Group Description	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 of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	1	1	1
After first dose (Day 0)	27.7 (NA)	219 (NA)	163 (NA)
After second dose (Day 28)	34.5 (NA)	255 (NA)	235 (NA)
After third dose (Day 56)	33.4 (NA)	338 (NA)	251 (NA)

13. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Arm/Group Description	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 of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	1	1	1
After first dose (Day 0)	4.84 (NA)	51.8 (NA)	52.8 (NA)
After second dose (Day 28)	7.91 (NA)	54.1 (NA)	64.4 (NA)
After third dose (Day 56)	9.70 (NA)	85.5 (NA)	68.4 (NA)

14. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Arm/Group Description	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 of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	1	1	1
After first dose (Day 0)	335 (NA)	2820 (NA)	2090 (NA)
After second dose (Day 28)	408 (NA)	4720 (NA)	3080 (NA)
After third dose (Day 56)	499 (NA)	3690 (NA)	3420 (NA)

15. Secondary Outcome

Title	Accumulation Ratio for CAT-354 (RA)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Arm/Group Description	CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	1	1	1
RA for Cmin	1.20 (NA)	1.54 (NA)	1.73 (NA)
RA for Cmax	2.00 (NA)	1.65 (NA)	1.30 (NA)
RA for AUC	1.49 (NA)	1.31 (NA)	1.64 (NA)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg
Arm/Group Description	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 1 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.	CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Measure Participants	3	2	4	4
TEAEs	2 66.7%	2 66.7%	4 100%	3 75%
TESAEs	0 0%	0 0%	0 0%	1 25%

Adverse Events

Time Frame	Day 0 to 84
Arm/Group Title	Placebo		CAT-354 1 mg/kg		CAT-354 5 mg/kg		CAT-354 10 mg/kg
Arm/Group Description	Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56		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 of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.		CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
All Cause Mortality
	Placebo		CAT-354 1 mg/kg		CAT-354 5 mg/kg		CAT-354 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		CAT-354 1 mg/kg		CAT-354 5 mg/kg		CAT-354 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)		0/4 (0%)		1/4 (25%)
Immune system disorders
Hypersensitivity	0/3 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Placebo		CAT-354 1 mg/kg		CAT-354 5 mg/kg		CAT-354 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/2 (100%)		4/4 (100%)		2/4 (50%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Constipation	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Diarrhoea	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Nausea	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Vomiting	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	2	1/4 (25%)	1
General disorders
Chest discomfort	0/3 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Inflammation	0/3 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Immune system disorders
Seasonal allergy	0/3 (0%)	0	0/2 (0%)	0	0/4 (0%)	0	2/4 (50%)	3
Infections and infestations
Nasopharyngitis	2/3 (66.7%)	2	2/2 (100%)	2	1/4 (25%)	1	1/4 (25%)	1
Urinary tract infection	1/3 (33.3%)	1	0/2 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Investigations
Forced expiratory volume decreased	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Musculoskeletal pain	0/3 (0%)	0	1/2 (50%)	1	0/4 (0%)	0	0/4 (0%)	0
Nervous system disorders
Headache	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Hypoaesthesia	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/3 (33.3%)	2	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Dyspnoea exertional	0/3 (0%)	0	1/2 (50%)	1	0/4 (0%)	0	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/3 (0%)	0	0/2 (0%)	0	1/4 (25%)	1	0/4 (0%)	0

Limitations/Caveats

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.

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Certain Agreements

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

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.