E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Eosinophilic Asthma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068462 |
E.1.2 | Term | Eosinophilic asthma |
E.1.2 | System Organ Class | 100000015470 |
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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 determine the effect of OC000459 on induced sputum eosinophil counts at 12 weeks of treatment compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of OC000459 on pre- and post-bronchodilator spirometry (FEV1/FVC), FeNO, ACQ-5 and AQLQ(S), and induced sputum eosinophil count compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent to participate in the study.
2. Be age 18 years and over.
3. Show evidence of reversible airflow obstruction documented within the previous 24 months or prior to Randomisation by one of the following measures:
• airway reversibility (>12% increase in FEV1 and 200ml following 2.5mg nebulised salbutamol),
• airway hyper-responsiveness (methacholine provocative concentration (PC20) causing a 20% fall in FEV1 of ≤8 mg/mL),
• airflow variability in clinic FEV1 ≥15% between two consecutive clinic visits, or airflow variability as indicated by >20% diurnal variability in PEF observed on 3 or more days.
4. Meet the ERS/ATS criteria for severe asthma at Screening:
• A high dose inhaled corticosteroid and long acting β2-agonist or leukotriene modifier/theophylline used for the previous year
• or OCS used for ≥50% of the previous year.
5. Have documented evidence of eosinophilic airway inflammation during the 24 months prior to Screening:
• an induced sputum eosinophil count ≥3%;
• or a peripheral blood eosinophil count ≥0.25 x 109/l that was related to asthma
• or an exhaled nitric oxide concentration (FeNO) >50 ppb.
6. Have evidence of eosinophilic airway inflammation at Screening as reflected by an induced sputum eosinophil count of ≥3%.
7. Subjects who are taking OCS must be receiving a 20 mg prednisolone equivalent dose or less daily for at least four weeks before the first dose of study drug. The dose of OCS should be unchanged for at least 14 days prior to the Baseline visit.
8. Able to comply with the study protocol.
9. Women of child bearing potential must have a negative pregnancy test at Screening and on Day 1 and be prepared to use two forms of reliable contraception (hormonal, either oral or implant; intrauterine device; intravaginal barrier device; condom) during the study and for three months thereafter.
10. Male subjects with female partners of child bearing potential must agree to take adequate contraceptive precautions for the entire duration of study participation. |
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E.4 | Principal exclusion criteria |
1. Treatment with XolairTM or anti-Th2 biologicals within 6 months prior to screening.
2. Subjects with clinically significant abnormal serum biochemistry, haematology and urine examination values (not associated with the study indication) within 21 days of the first dose.
3. Subjects who have been hospitalised in the last 3 months.
4. History of more than 2 episodes of confirmed bacterial lower respiratory tract infection or current lower respiratory tract infection.
5. Subjects who are current smokers or have a smoking history of >15 pack years.
6. Significant comorbidity that in the Investigator’s opinion is likely to impact the subject’s participation in a 26 week study.
7. Presence of a clinically important lung condition other than asthma, e.g. malignancy or previous history of cancer in remission for less than 12 months, clinically important liver or kidney disease, uncontrolled clinically significant cardiovascular or metabolic disease, hypereosinophilic syndromes such as Churg-Strauss Syndrome or eosinophilic oesophagitis.
8. Receipt of any of the following medications – more than 1g of paracetamol per day, prednisolone at a dose of more than 20mg per day, regular nonsteroidal anti-inflammatory drugs (NSAIDs) for more than 3 days in the two weeks prior to randomisation.
9. A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to screening, or positive drugs of abuse result at screening.
10. Participation in another clinical study (observational or interventional) within 3 months of the first dose of study drug or at any time during this study. Studies that require consent only to store data and that do not require follow up are not considered to be observational or interventional and are exempt from this exclusion.
11.A history of hypersensitivity and/or idiosyncrasy to any of the test compounds or excipients employed in this study (see section 6).
12.Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
13.Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
14. Subjects with ALT or AST at screening ≥2xULN.
15. Subjects with active hepatitis, chronic active hepatitis or evidence of chronic liver disease (e.g. alcoholic liver disease, fatty liver disease, autoimmune hepatitis, etc.) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is fold change in induced sputum eosinophil count from baseline to Week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are change from Baseline in the following:
• Induced sputum eosinophil count at Week 12
• ACQ-5 at Weeks 4, 8 and 12
• AQLQ(S) at Weeks 4, 8 and 12
• FeNO at Weeks 4, 8, and 12
• FEV1 and FVC before and 20 minutes after 2.5 mg inhaled salbutamol at Weeks 4, 8, and 12
• Induced sputum eosinophil count at Weeks 4 and 8 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 |