Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000444482
Ethics application status
Approved
Date submitted
22/08/2007
Date registered
31/08/2007
Date last updated
20/10/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
A Double Blind, Placebo Controlled Parallel Group Study to Assess the Efficacy, Safety and Tolerability of CAT-354 in Subjects with Uncontrolled Asthma Despite Optimal Treatment
Scientific title
A Double Blind, Placebo Controlled Parallel Group Study to Assess the Efficacy, Safety and Tolerability of CAT-354 in Subjects with Uncontrolled Asthma Despite Optimal Treatment
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uncontrolled Asthma 2029 0
Condition category
Condition code
Respiratory 2120 2120 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CAT-354 (Anti-IL-13 HuMab) recombinant human monoclonal antibody of the G4 subclass that neutralises interleukin-13 (IL-13).

Each subject will receive intravenous infusions with CAT-354 or placebo. Dose will be adjusted to body weight.
CAT-354 at the following doses:
- 1 mg/kg CAT-354 on Day 0, 28, and 56;
- 5 mg/kg CAT-354 on Day 0, 28, and 56;
- 10 mg/kg CAT-354 on Day 0, 28, and 56.

Patient participation will be a maximum of 112 days (including a 14 to 28 day screening period)
Intervention code [1] 1882 0
Treatment: Drugs
Comparator / control treatment
Placebo to match all doses of CAT-354 on Day 0, 28, and 56.
Control group
Placebo

Outcomes
Primary outcome [1] 3243 0
To investigate the effects of CAT-354 on airway hyperresponsiveness (AHR) in uncontrolled asthma.
Timepoint [1] 3243 0
Visit 1, Day -28/-14 to Day 0
Visit 2, Day -1/0
Visit 4, Day 14
Visit 5, Day 27/28
Visit 7, Day 56
Visit 9, Day 84/Termination visit
Secondary outcome [1] 5003 0
To obtain additional efficacy data and data on dose response;
Timepoint [1] 5003 0
Length of study
Secondary outcome [2] 5004 0
To extend the safety and tolerability database of CAT-354;
Timepoint [2] 5004 0
Length of study
Secondary outcome [3] 5005 0
To obtain further data on the pharmacokinetics/pharmacodynamics of CAT-354;
Timepoint [3] 5005 0
Length of study
Secondary outcome [4] 5006 0
To extend the CAT-354 immunogenicity database.
Timepoint [4] 5006 0
Length of study

Eligibility
Key inclusion criteria
Signed and dated written informed consent is obtained prior to any study related procedure taking place.
- Women either infertile (e.g. hysterectomised, sterile or post menopausal with amenorrhoea of least one year duration) or who are practicing an acceptable form of birth control (contraceptive pill or double-barrier contraception - partner using condom and subject using spermicide, diaphragm, intra-uterine device or contraceptive sponge) for greater than 2 months prior to Visit 1 (screening visit). Women of childbearing potential must continue to practice birth control during the study and for at least 2 months after completing the study. Women of childbearing potential must have a negative pregnancy test at screening and Visit 2.
- Uncontrolled asthma despite optimal treatment - subjects will have Global Initiative for Asthma (GINA 2006) clinical features of uncontrolled asthma despite treatment with a minimum dose of 800 µg beclomethasone dipropionate or equivalent inhaled corticosteroid per day plus one or more additional controller i.e. long-acting beta-agonist, leukotriene antagonist or theophylline. Oral corticosteroids (not parenteral) as additional treatment at any dose are acceptable. The dose of inhaled and oral corticosteroids must have been stable within 4 weeks preceding Visit 1 (screening visit) and will be expected to remain stable for the duration of the study. If subjects are on single inhaler combination products at Visit 1 (e.g. fluticasone/salmeterol - Advair®/Seretide® or Symbicort (budesonide/formoterol) SMART®) they must receive the two components as two separate inhaler medications for the purpose of the trial. This will facilitate withholding the long-acting beta-agonist component before lung function and challenge testing
- A forced expiratory volume in 1 second (FEV1) acceptable for AHR challenge tests ( = 60% of predicted normal).
- A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) = 4 mg/mL
- Aged 18-80 years and are ambulatory and able to travel to the clinic.
- A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities.
- Clinical chemistry, haematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator.
- Maximum body weight of 130 kg.
- No other clinically significant abnormality on history and clinical examination.
- Able to comply with the requirements of the protocol.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Experienced a severe exacerbation within 28 days preceding Visit 1.
- Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Visit 1. Subjects with a history of allergic rhinitis, seasonal allergy or oesophagitis must be optimally controlled and remain on a stable treatment regimen during the study.
- Participation in another study within five half lives or three months of the start of this study, whichever is the longer. This does not apply to methodological or observational studies in which no investigational medicinal product (IMP) was given.
- Lower respiratory tract infection within six weeks of Visit 1.
- Any acute illness in the two weeks before Visit 1.
- Current smokers or ex-smokers with greater than 10 pack-years (number of pack years = (number of cigarettes per day/20) x number of years smoked, e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years).
- Blood donation (more than 550 mL) in the previous two 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 Visit 1 (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 > 200 mmHg, or diastolic blood pressure > 100 mmHg), heart disease, psoriasis requiring treatment). Subjects who have had a heart attack or stroke within 3 months preceding Visit 1 or who have a known aneurysm.
- Lack of control of asthma caused by coexisting conditions such as rhinitis or gastro-oesophageal reflux disease.
- Subject is a participating Investigator, sub-investigator, study co-ordinator, or employee of a participating Investigator, or is an immediate family member of the aforementioned.
- Any factor which, in the opinion of the Investigator, would jeopardise the evaluation or safety or be associated with poor adherence to the protocol (i.e. inability to complete study diary, perform PEF measurements).
- The subject’s primary care physician recommends the subject should not take part in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The randomisation will proceed according to a centre-specific, computer-generated randomisation code. Randomisation will be conducted through the use of IVRS (Interactive Voice Response System)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomisation will be performed based on atopic and non-atopic status, by country and if possible by centre.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/09/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
228
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 526 0
Germany
State/province [1] 526 0
Country [2] 527 0
Russian Federation
State/province [2] 527 0
Country [3] 528 0
Poland
State/province [3] 528 0
Country [4] 529 0
Netherlands
State/province [4] 529 0
Country [5] 530 0
United Kingdom
State/province [5] 530 0

Funding & Sponsors
Funding source category [1] 2273 0
Commercial sector/Industry
Name [1] 2273 0
Cambridge Antibody Technology
Country [1] 2273 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Cambridge Antibody Technologies
Address
Milstein Building, Granta Park
Cambridge CB21 6GH
Country
United Kingdom
Secondary sponsor category [1] 2054 0
Commercial sector/Industry
Name [1] 2054 0
PRA International
Address [1] 2054 0
Suite 1701, 323 Castlereagh Street
Sydney NSW 200
Country [1] 2054 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4420 0
Ethics committee address [1] 4420 0
Ethics committee country [1] 4420 0
Date submitted for ethics approval [1] 4420 0
18/07/2007
Approval date [1] 4420 0
Ethics approval number [1] 4420 0
Ethics committee name [2] 4500 0
Bellberry Limited
Ethics committee address [2] 4500 0
South Australia
Ethics committee country [2] 4500 0
Australia
Date submitted for ethics approval [2] 4500 0
Approval date [2] 4500 0
22/08/2007
Ethics approval number [2] 4500 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27696 0
Address 27696 0
Country 27696 0
Phone 27696 0
Fax 27696 0
Email 27696 0
Contact person for public queries
Name 11071 0
Professor Philip Thompson
Address 11071 0
The Lung Institute of Western Australia
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6066
Country 11071 0
Australia
Phone 11071 0
(08) 9346 3198
Fax 11071 0
(08) 9346 4159
Email 11071 0
p.thomps@cyllene.uwa.edu.au
Contact person for scientific queries
Name 1999 0
Professor Philip Thompson
Address 1999 0
The Lung Institute of Western Australia
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6066
Country 1999 0
Australia
Phone 1999 0
(08) 9346 3198
Fax 1999 0
(08) 9346 4159
Email 1999 0
p.thomps@cyllene.uwa.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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