Phase I study to assess the safety and tolerability of inhaled interferon-beta (IFN-beta1a) in controlled asthmatic male and female subjects

INTERVENTION: There will be 4 cohorts with 10 subjects in each cohort. The study medication is IFN‐beta1a (IFN‐beta1a plus excipient) and the placebo is the same excipient only. 1. Cohort 1 will receive a low dose of either IFN‐beta1a or placebo as a single dose only 2. Cohort 2 will receive a mid dose of either IFN‐beta1a or placebo as a single dose and then if all safety parameters are within acceptable ranges they will move on to multiple dosing once every 3 days for a 14 day period (5 doses in total, excluding the single dose) 3. Cohort 3 will receive the highest proposed dose of either IFN‐beta1a or placebo as a single dose and then if all safety parameters are within acceptable ranges they will move on to multiple dosing once every 3 days for a 14 day period (5 doses in total, excluding the single dose) 4. Cohort 4 will also receive the highest dose of either IFN‐beta1a or placebo as a single dose and then if all safety parameters are within acceptable ranges they will move on to multiple dosing, once a day for 14 days (14 doses excluding the single dose) Both the IFN‐beta1a and the placebo will be administered via inhalation using the CE marked I‐neb® device manufactured by Respironics Respiratory Drug Delivery (UK) Limited. For all treatment arms, follow up is for 2 weeks post the last dose of study medication. However, there are also optional follow up visits, whereby subjects will be requested to repeat any measurements which are outside of the acceptable ranges until they either return to within the acceptable range or the Investigator is satisfied that the measurements should stop. Therefore follow up could be for longer then 2 weeks. However, if all measurements are within acceptable ranges and there are no ongoing adverse events, follow up will only be for 2 weeks post their last dose of study medication. CONDITION: Asthma ; Respiratory ; Asthma PRIMARY OUTCOME: The primary endpoints will be the assessment of respiratory function:; 1. FEV1, measured at V1, V3.2, V3.3 (at 20 and 40 minutes, 1, 2, 4, 8 and 12 hours), V3.4, V4, V7.2, V7.3 (at 20 and 40 minutes, 1, 2, 4, 8 and 12 hours), V7.4, V8, V9, V10, V11, V12 and V13; 2. Forced vital capacity (FVC), measured at V1, V3.2, V3.3 (at 20 and 40 minutes, 1, 2, 4, 8 and 12 hours), V3.4, V4, V7.2, V7.3 (at 20 and 40 minutes, 1, 2, 4, 8 and 12 hours), V7.4, V8, V9, V10, V11, V12 and V13; 3. TLCO, measured at V1, V3.2, V3.4, V4, V7.2, V7.4, V8, V9, V10, V11, V12 and V13; 4. Fraction of exhaled nitric oxide (FENO) levels, measured at V1, V3.1. V3.2, V3.4, V4, V7.1, V7.2, V7.4, V8, V9, V10, V11 and V12; 5. Significant changes in sputum eosinophils counts, measured at V2, V3.4, V7.4 and V12; ; Timepoints:; Single dose:; V1 (screen 1): day ‐14 to ‐5; V2 (screen 2): day ‐10 to ‐2; V3.1 (night before dosing): ‐1 day (‐ 12 hours); V3.2 (dosing day pre‐dose): Day 0A ; V3.3 (dosing day post‐dosing): Day 0A ; V3.4 (24 hours post‐dosing): Day 1A; V4 (follow‐up): Day 3A; V5 (telephone follow‐up): 15 +/‐ 1 day; V6 (follow up): subjects in cohort 2, 3 and 4 will continue into multiple dosing if they meet the criteria. If they do not meet the criteria then they will require follow up visit 6. ; ; Multiple dose:; V7.1 (night before dosing): ‐1 day (‐12 hours); V7.2 (1st multiple dose day pre‐dose): Day 0B ; V7.3 (dosing day post‐dose): Day 0B ; V7.4 (24 hours post‐dosing): Day 1B; V8/V9/V10/V11: Day 1B+3, 6, 9, 12 days; V12 (follow‐up 1): 3 days post EOT; V13 (follow‐up 2): 5 days post EOT; V14 (telephone follow‐up +/‐1 day): 15 days EOT; V15 (follow‐up): optional SECONDARY OUTCOME: The clinical review and interpretation of general safety measurements including the investigation of pharmacokinetics over time will be secondary endpoints. INCLUSION CRITERIA: To be eligible for inclusion into this study, each subject must fulfil the following criteria: 1. Diagnosis of controlled asthma requiring regular inhaled corticosteroids (ICS). Subjects must have been taking the same dose of ICS regularly for six weeks prior to Screening Visit one. 2. Forced expiratory volume in one second (FEV1) is equal to or greater than 80% predicted and diffusing capacity of the lung for carbon monoxide (DLCO/TLCO) equal to or greater than 80% predicted (pre‐bronchodilator) 3. Presence of bronchial hyperresponsiveness as measured by a methacholine challenge which results in a provocative concentration causing a 20% fall in FEV1 (PC20) equal to or less than 16 mg/ml 4. Stable asthma, indicated by asthma symptoms and bronchodilator usage equal to or less than three times a week when needed to relieve symptoms. In addition to this, bronchodilator usage equal to or less than once a day if taken as a preventative prior to exercise will