E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effects of CAT-354 on airway hyperresponsiveness (AHR) in uncontrolled (refractory) asthma. |
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E.2.2 | Secondary objectives of the trial |
To obtain additional efficacy data and data on dose response.
To extend the safety and tolerability database of CAT-354.
To obtain further data on the pharmacokinetics/pharmacodynamics of CAT-354.
To extend the CAT-354 immunogenicity database. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 1 month prior to Visit 1 (screening visit) or longer if requested by the investigator. 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 β-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 β-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 (see also Exclusion Criteria).
11. Able to comply with the requirements of the protocol.
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E.4 | Principal exclusion criteria |
1. Experienced a severe exacerbation (according to the criteria listed in Section 9.6.1.1) within 28 days preceding Visit
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 observational studies in which no investigational medicinal product (IMP) was given.
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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The doubling concentration of methacholine will be measured at Visit 5 as compared with the pre dose Visit 2 value |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |