A double-blind, placebo-controlled parallel-group study to assess the efficacy, safety, and tolerability of CAT-354

• Conditions: Asthma; MedDRA version: 9.1Level: PTClassification code 10003553Term: Asthma

• Registration Number: EUCTR2007-002090-31-DE
• Lead Sponsor: MedImmune Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Signed and dated written informed consent is obtained prior to any study related procedure taking place.
2. 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, 5, 7 and 9.
3. Uncontrolled (refractory) 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 b-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 b-agonist component before lung function and challenge testing (see Section 9.5.7).
4. A forced expiratory volume in 1 second (FEV1) acceptable for AHR challenge tests (= 60% of predicted normal) on the challenge days.
5. A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) = 4 mg/mL (see also the continuation criteria in Section 9.4.3.2).
6. Aged 18-80 years and are ambulatory and able to travel to the clinic.
7. A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities.
8. Clinical chemistry, haematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator (see Section 11.10 of the protocol for explanation on tests to be performed).
9. Subjects aged between 18 - 40 years inclusive must have a BMI of 18 - 32 kg/m2 inclusive. Subjects aged between 41 and 80 years inclusive must have a BMI 18 - 35 kg/m2.
10. No other clinically significant abnormality on history and clinical examination.
11. Able to comply with the requirements of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Experienced a severe exacerbation (according to the criteria listed in Section 9.6.1.1) within 28 days preceding Visit 1.
2. Onset of uncontrolled seasonal allergy symptoms within 7 days preceding Visit 1. Subjects with a history of allergic rhinitis, seasonal allergy or oesophagitis must be optimally controlled.
3. 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
4. Lower respiratory tract infection within six weeks of Visit 1.
5. 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).
6. Blood donation (more than 550 mL) in the previous two months.
7. Excessive intake of alcohol (as judged by the Investigator) or evidence of drug or solvent abuse.
8. 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.
9. Concurrent medication from Visit 1 (screening visit) and for the duration of the study with any of the prohibited medications listed in Section 9.5.7.
10. Any chronic disease that is clinically unstable and may jeopardise the safety of the subject in the investigator's opinion or that may require treatment with medications prohibited by the protocol.
11. 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.
12. 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).
13. The subject’s primary care physician recommends the subject should not take part in the study.
14. Known hypersensitivity to CAT-354 or its components, to methacholine or to related drugs.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effects of CAT-354 on airway hyperresponsiveness (AHR) in uncontrolled (refractory) asthma. ;Secondary Objective: To obtain additional efficacy data and data on dose response.<br>To extend the safety and tolerability database of CAT-354.<br>To obtain further data on the pharmacokinetics/pharmacodynamics of CAT-354.<br>To extend the CAT-354 immunogenicity database.;Primary end point(s): The doubling concentration of methacholine will be measured at Visit 5 as compared with the pre dose Visit 2 value