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

• Register: ANZCTR
• Last refreshed on: 22 February 2013
• Main ID: ACTRN12607000444482
• Date of registration: 31/08/2007
• Primary sponsor: Commercial sector/Industry Cambridge Antibody Technologies
• 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
• Date of first enrolment: 1/09/2007
• Target sample size: 228
• Recruitment status: Terminated
• URL: http://www.anzctr.org.au/ACTRN12607000444482.aspx
• Study type: Interventional
• Study design: Randomised controlled trial Parallel

Countries of recruitment

Australia, Germany, Netherlands, Poland, Russian Federation, United Kingdom

Contacts

• Name: Professor Philip Thompson

• Name: Professor Philip Thompson

Key inclusion & exclusion criteria

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.
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.

Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Uncontrolled Asthma

Intervention(s)

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)

Primary Outcome(s)

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

Secondary Outcome(s)

To extend the CAT-354 immunogenicity database.

To extend the safety and tolerability database of CAT-354;

To obtain additional efficacy data and data on dose response;

To obtain further data on the pharmacokinetics/pharmacodynamics of CAT-354;

Source(s) of Monetary Support

Cambridge Antibody Technology

Secondary Sponsor(s)

PRA International