A Study to Assess Pharmacokinetics, Safety and Tolerability of Multiple Doses of CAT-354 in Subjects With Moderate Asthma

Study identifier:CAT-354-0602

ClinicalTrials.gov identifier:NCT00974675

EudraCT identifier:2006-003199-36

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Double-Blind, Placebo Controlled Study to Assess the Pharmacokinetics, Safety and Tolerability of Multiple Intravenous Doses of 3 Dose Levels of CAT-354 in Subjects With Moderate Asthma

Medical condition

Moderate Asthma

Phase

Phase 1

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 60 Years

Date

Study Start Date: 29 Sept 2006

Primary Completion Date: 03 Aug 2007

Study Completion Date: 03 Aug 2007

Study design

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

Verification:

Verified 01 Mar 2017 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Males or infertile females
- Subjects with asthma, well controlled on inhaled corticosteroid and taken as required (PRN) short acting beta 2 agonist therapy only
- Unchanged dose of inhaled corticosteroid for 3 months prior to Day 0 and no expected need for change in dose during study
- Forced expiratory volume in 1 second (FEV1) greater than or equal to 80% predicted at Screening (Baseline)
- 18-60 years
- General Practitioner diagnosis of asthma of 1 year's minimum duration (with respect to Day 0)
- No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history)
- 12-lead electrocardiogram with no clinical significant abnormality
- Clinical chemistry hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
- A negative screen for drugs of abuse and alcohol
- Body weight between 50-120 kg
- Subjects aged between 18-40 years inclusive must have body mass index (BMI) 18-32 kilogram per square meter (kg/m^2) inclusive. Subjects aged between 41-60 years must have BMI between 18-30 kg/m^2 inclusive.

Exclusion Criteria

- Active concomitant disease, with exception of eczema
- Expected onset of seasonal allergy before the administration of the last dose of study medication
- History of severe exacerbation within 3 years of Day 0
- Recorded use of inhaled short acting beta 2 agonist medication for symptoms within 14 days of Day 0 of: More than 6 doses per day on any 1 day or more than 3 doses per day on 6 or more days
- Any medication other than: inhaled short-acting beta 2 agonist, inhaled corticosteroids, topic eczema treatments (with the exception of fluorinated corticosteroid, dermatological preparations which are not permitted), hormone replacement therapy, vitamin preparation/food supplements, occasional use of proton pump inhibitors, ranitidine, cimetidine, antacids or over-the-counter analgesics
- Treatment within 6 months of Day 0 with any of the following: methylxanthines, inhaled cromones, leukotriene modifiers, anti- immunoglobulin E (IgE), anticholinergics, ketotifen, oral short acting B2 agonists, long-acting B2 agonists, oral or injected corticosteroids
- Treatment of atopic symptoms, other than eczema, within 4 weeks of Day 0
- History of medication that might carry-over effects into the study
- Previously received monoclonal antibody, or a similar related protein, that might sensitize to CAT-354
- Participation in another study within three months of the start of the study or 5 half lives of the previously administered investigational medicinal product (IMP), whichever is longer
- Lower respiratory tract infection within 4 weeks of Day-14
- Any acute illness in the two weeks before Day 0
- Current smokers, those who have smoked in previous year, and those with smoking history of greater than or equal to 10 pack years
- Considered by the investigator to be at risk of transmitting, through blood, the agents responsible for infectious diseases
- Blood donation (550 ml) in the previous 2 months
- Excessive intake of alcohol (more than 21 units a week for females or 28 units a week for males)
- The subject's general practitioner has suggested a reason the subject should not participate in the study
- The Investigator considers the subject should not take part for any reason.

Location

Chiltern International Limited

Slough, Berkshire, United Kingdom, SL1 2AD

Arms	Assigned Interventions
Experimental: CAT-354 1 mg/kg CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.	Biological/Vaccine: CAT-354 1mg/kg CAT-354 1 mg/kg of body weight intravenous infusion over 30 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 30 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 30 minutes on Day 0, 28 and 56. Other Name: Tralokinumab
Experimental: CAT-354 10mg/kg CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.	Biological/Vaccine: CAT-354 10mg/kg CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56. Other Name: Tralokinumab
Placebo Comparator: Placebo Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.	Other: Placebo Placebo matched to CAT-354 intravenous infusion over 30 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
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Placebo	Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Participant Flow: Overall Study

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg	Placebo
STARTED	8	8	3	4
COMPLETED	6	7	1	2
NOT COMPLETED	2	1	2	2
Adverse Event	2	1	1	1
Physician Decision	0	0	1	0
Participant on holiday; unable to attend	0	0	0	1

Baseline Characteristics

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

Safety population included all participants who received at least 1 dose of investigational medicinal product (IMP: CAT-354 or placebo) including those who did not complete the study.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Placebo	Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Baseline Measures

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg	Placebo	Total
Number of Participants [units: Participants]	8	8	3	4	23
Gender, Male/Female [units: participants]
Female	0	0	1	0	1
Male	8	8	2	4	22
Age Continuous [units: years] Mean ± Standard Deviation	39.4 ± 9.07	34.6 ± 7.58	43.3 ± 14.47	40.0 ± 13.04	38.3 ± 9.80

Outcome Measures

1. Primary Outcome Measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]

Measure Type	Primary
Measure Name	Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose
Measure Description
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	8	3
Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose [units: microgram/milliliter (mcg/mL)] Mean (Standard Deviation)	30.3 (5.18)	156.8 (34.55)	306.3 (31.39)

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

2. Primary Outcome Measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35 ]

Measure Type	Primary
Measure Name	Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose
Measure Description
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	7	7	1
Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose [units: mcg/mL] Mean (Standard Deviation)	35.0 (6.81)	161.0 (32.81)	298.0 (NA)^[1]

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

3. Primary Outcome Measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147 ]

Measure Type	Primary
Measure Name	Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose
Measure Description
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	6	7	1
Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose [units: mcg/mL] Mean (Standard Deviation)	41.1 (4.77)	178.7 (25.41)	393.0 (NA)^[1]

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

4. Primary Outcome Measure: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]

Measure Type	Primary
Measure Name	Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose
Measure Description
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	8	3
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose [units: (mcg*day)/mL] Mean (Standard Deviation)	299.6 (42.03)	1691.3 (302.70)	3106.3 (719.25)

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 After First Dose

5. Primary Outcome Measure: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - infinity]) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]

Measure Type	Primary
Measure Name	Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - infinity]) for CAT-354 After First Dose
Measure Description	AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	8	3
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - infinity]) for CAT-354 After First Dose [units: (mcg*day)/mL] Mean (Standard Deviation)	428.0 (83.33)	2314.3 (392.91)	3861.3 (662.42)

No statistical analysis provided for Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - infinity]) for CAT-354 After First Dose

6. Primary Outcome Measure: Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]

Measure Type	Primary
Measure Name	Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose
Measure Description	Terminal elimination phase half-life is the time measured for the serum concentration to decrease by one half.
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	8	3
Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose [units: days] Mean (Standard Deviation)	16.6 (2.67)	16.1 (3.60)	11.8 (1.86)

No statistical analysis provided for Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose

7. Primary Outcome Measure: Clearance (CL) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]

Measure Type	Primary
Measure Name	Clearance (CL) for CAT-354 After First Dose
Measure Description	Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance was normalized by the body weight of the participant.
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	8	3
Clearance (CL) for CAT-354 After First Dose [units: (mL/day)/kilogram] Mean (Standard Deviation)	2.41 (0.45)	2.23 (0.46)	2.64 (0.42)

No statistical analysis provided for Clearance (CL) for CAT-354 After First Dose

8. Primary Outcome Measure: Volume of Distribution (Vd) for CAT-354 After First Dose [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 ]

Measure Type	Primary
Measure Name	Volume of Distribution (Vd) for CAT-354 After First Dose
Measure Description	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Volume of distribution was normalized to the body weight of the participant.
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	8	3
Volume of Distribution (Vd) for CAT-354 After First Dose [units: mL/kg] Mean (Standard Deviation)	56.7 (8.04)	51.0 (10.36)	44.0 (0.79)

No statistical analysis provided for Volume of Distribution (Vd) for CAT-354 After First Dose

9. Primary Outcome Measure: Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose [ Time Frame: Pre-dose on Day 28 ]

Measure Type	Primary
Measure Name	Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose
Measure Description
Time Frame	Pre-dose on 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.
PK population included all participants in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	8	7	1
Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose [units: mcg/mL] Mean (Standard Deviation)	5.3 (1.33)	27.1 (4.91)	40.7 (NA)^[1]

No statistical analysis provided for Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose

10. Primary Outcome Measure: Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose [ Time Frame: Pre-dose on Day 56 ]

Measure Type	Primary
Measure Name	Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose
Measure Description
Time Frame	Pre-dose on Day 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 in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	6	7	1
Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose [units: mcg/mL] Mean (Standard Deviation)	7.7 (1.63)	36.0 (11.51)	59.4 (NA)^[1]

No statistical analysis provided for Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose

11. Primary Outcome Measure: Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose [ Time Frame: Day 84 ]

Measure Type	Primary
Measure Name	Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose
Measure Description
Time Frame	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.
PK population included all participants in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	6	7	1
Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose [units: mcg/mL] Mean (Standard Deviation)	8.6 (1.99)	40.6 (12.26)	79.6 (NA)^[1]

No statistical analysis provided for Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose

12. Primary Outcome Measure: Accumulation Ratio (R0) for CAT-354 [ Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0 and 56; Pre-dose on Day 28; Day 4, 7, 14, 21, 63 and 84 ]

Measure Type	Primary
Measure Name	Accumulation Ratio (R0) for CAT-354
Measure Description	Accumulation ratio is calculated as: R0 = AUC(56 - 84)/AUC(0 - 28) where AUC(0 - 28) and AUC(56 - 84) are the area under the serum concentration time curve over a dosage interval determined after the first dose (Day 0 to Day 28) and after the third dose (Day 56 to Day 84), respectively.
Time Frame	Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0 and 56; Pre-dose on Day 28; Day 4, 7, 14, 21, 63 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.
PK population included all participants in the safety population for whom sufficient post-dose blood samples were taken to estimate a Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 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]	6	7	1
Accumulation Ratio (R0) for CAT-354 [units: ratio] Mean (Standard Deviation)	1.58 (0.21)	1.39 (0.10)	1.67 (NA)^[1]

No statistical analysis provided for Accumulation Ratio (R0) for CAT-354

13. Secondary Outcome Measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 0 to Day 147 ]

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 147 that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Day 0 to Day 147
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 IMP (CAT-354 or placebo) including those who did not complete the study.

Reporting Groups

	Description
CAT-354 1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
CAT-354 10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Placebp	Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Measured Values

	CAT-354 1 mg/kg	CAT-354 5 mg/kg	CAT-354 10 mg/kg	Placebp
Number of Participants Analyzed [units:participants]	8	8	3	4
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [units: participants]
TEAEs	8	8	3	4
TESAEs	0	1	0	0

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 147
Additional Description	No text entered.

Reporting Groups

	Description
1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Placebo	Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Serious Adverse Events

1 mg/kg

5 mg/kg

10 mg/kg

Placebo

Total, serious adverse events

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

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

Other Adverse Events

Time Frame	Day 0 to 147
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
1 mg/kg	CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
5 mg/kg	CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
10 mg/kg	CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.
Placebo	Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.

Other Adverse Events

1 mg/kg

5 mg/kg

10 mg/kg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

8/8 (100.00%)

3/3 (100.00%)

4/4 (100.00%)

Eye disorders

Blepharospasm¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

0/8 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Epigastric discomfort¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Chest discomfort¹,^†

# participants affected / at risk

0/8 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

# events

General disorders and administration site conditions

Feeling hot and cold¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Infusion site pain¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

5/8 (62.50%)

7/8 (87.50%)

2/3 (66.67%)

3/4 (75.00%)

# events

Infections and infestations

Pertussis¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Infections and infestations

Tonsillitis¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Injury, poisoning and procedural complications

Procedural pain¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Investigations

Urine analysis abnormal¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Tendonitis¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Nervous system disorders

Disturbance in attention¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/8 (37.50%)

4/8 (50.00%)

1/3 (33.33%)

2/4 (50.00%)

# events

Nervous system disorders

Lethargy¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

1/8 (12.50%)

0/3 (0.00%)

1/4 (25.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

1/3 (33.33%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sinus congestion¹,^†

# participants affected / at risk

0/8 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

# events

Skin and subcutaneous tissue disorders

Eczema¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash papular¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/3 (0.00%)

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 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
Recruitment to the study was terminated before the planned number of participants was enrolled in CAT-354 10 mg/kg group due to the slow recruitment rate.

Results Point of Contact

Name/Title:	Meena Jain, MB BChir/Associate Medical Director
Organization:	MedImmune, LLC
Phone	301-398-0000
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

MedImmune LLC

MedImmune

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Chiltern International Limited

Trial Results Summaries