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| Phase I study to assess the safety and tolerability of inhaled interferon-beta (IFN-beta1a) in controlled asthmatic male and female subjects |
| Source of record | UK Trials |
| ISRCTN | ISRCTN83107787 |
| Date ISRCTN assigned | 27/02/2008 |
| Local reference number(s) | SG004 |
| Public title | Phase I study to assess the safety and tolerability of inhaled interferon-beta (IFN-beta1a) in controlled asthmatic male and female subjects |
| Scientific title | A double-blind, placebo controlled, single and multiple, dose-escalating, phase I study to assess the safety and tolerability of inhaled interferon-beta (IFN-beta1a) in controlled asthmatic male and female subjects |
| Acronym | N/A |
| Disease/condition/study domain | Asthma |
| Study hypothesis | To evaluate the safety and tolerability of both single and multiple doses of inhaled interferon-beta (IFN-beta1a), administered over a 14 day period to controlled asthmatic subjects. |
| Design/methodology | This study is a randomised, double-blind, placebo controlled, single and multiple, dose-escalating study. It is a multicentre study. |
| Research ethics review | Ethics approval pending from the Berkshire Research Ethics Committee (ref: 08/H0505/17). Committee sat on the 12th February 2008 - awaiting approval decision as of 14/02/2008. |
| Countries of trial | United Kingdom |
| Participants - 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 be allowed. 5. Male or female aged 18 to 55 years 6. Non-smoker or an ex-smoker who has stopped smoking for more than one year and has a smoking history of less than 10 pack-years 7. Written informed consent 8. Vital signs in the following normal range: 8.1. Oral body temperature: 35.0 - 37.5°C 8.2. Blood pressure: 8.2.1. After at least 3 min of rest, measured in the supine position: Systolic blood pressure: 90 - 140 mmHg Diastolic blood pressure: 50 - 90 mmHg 8.2.2. Then, after 3 minutes standing: Systolic blood pressure: no more than a 20 mmHg drop Diastolic blood pressure: no more than 10 mmHg drop 8.3. Pulse rate: after at least 3 min of rest, measured in supine position: 40 - 90 beats per minute (bpm) 8.4. Pulse oximetry greater then or equal to 95% 9. Motivation to complete all study visits, the ability to communicate well with the Investigator and be capable of understanding the nature of the research and its treatment including its risks and benefits |
| Participants - exclusion criteria | Any condition, including findings in the medical history or in the pre-study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for the participation of the subject into the study or that could interfere with the study objectives, conduct or evaluation. In particular: 1. Use of long acting bronchodilators 2. A change in dose of asthma medication during the past six weeks 3. Any clinically significant abnormality in the results of the pre-study safety laboratory tests 4. History of any lung disease other than asthma 5. Current participation in another clinical trial or participation in a clinical trial where the subject has received a dose of the test product (Investigational Medicinal Product [IMP]) within 12 weeks prior to entry into the study (for small molecules) and within 6 months prior to entry into the study (for biologicals) 6. Any clinically significant abnormality on the 12 lead resting electrocardiogram 7. History or presence of hypertension or other significant cardiovascular abnormality 8. Occurrence of any acute infection or disease within the last six weeks prior to screening 9. History of asthma exacerbation and/or upper/lower respiratory tract infection within six weeks prior to screening 10. History of hypersensitivity to natural or recombinant interferon-beta or to any of the drug preparation excipients 11. History of severe depressive disorders and/or suicidal ideation 12. History of liver disease or liver blood test abnormalities other than Gilbert's syndrome 13. History of epilepsy or seizures 14. Definite or suspected personal history of adverse drug reaction or hypersensitivity to drugs with a similar chemical structure to interferon 15. History or presence of drug or alcohol abuse 16. Loss or donation of more than 400 ml of blood within 12 weeks prior to entry into the study 17. Subjects who have taken any prescription drugs within 6 weeks, other than medication for the treatment of asthma and drugs used for the treatment of atopic dermatitis, atopic rhinitis and other allergic conditions. All other concomitant medications will be at the discretion of the Investigator. 18. Subjects who have taken over-the-counter medication, with the exception of multi-vitamins and paracetamol, within 1 week before drug administration. All other concomitant medications will be allowed at the discretion of the Investigator. 19. Subjects will undergo training during the screening phase to ensure their ability to use the I-neb® device. If subjects do not show sufficient proficiency in the use of the device, they will not be eligible for inclusion in the study. 20. Pregnancy either current or planned over the next 12 weeks. For those who are sexually active precautions are to be advised to both male and female subjects to avoid pregnancy during the trial and follow-up period. These precautions include pregnancy testing at screening, baseline and follow up, as well as the use of a highly effective method of birth control (i.e. the oral contraceptive pill or IUD and the use of condoms) or after surgical sterilisation (i.e. hysterectomy). Continued testing and monitoring will take place during the trial if required. |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Anticipated start date | 01/05/2008 |
| Anticipated end date | 01/03/2009 |
| Status of trial | Ongoing |
| Target number of participants | 40 subject will be entered into the study |
| Interventions | 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 exipient 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 evey 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 admisiterd 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. |
| Primary outcome measure(s) | 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 measure(s) | The clinical review and interpretation of general safety measurements including the investigation of pharmacokinetics over time will be secondary endpoints. |
| Sources of funding | Synairgen Research Limited (UK) |
| Sponsor name | Synairgen Research Limited (UK) |
| Sponsor details | Mailpoint 810 Level F, South Block Southampton General Hospital Tremona Road Southampton United Kingdom SO16 6YD |
| Sponsor website | http://www.synairgen.com |
| Contact name | Prof Ratko Djukanovic |
| Contact details | Mailpoint 810 Level F, South Block Southampton General Hospital Tremona Road Southampton United Kingdom SO16 6YD |
| More information | For more up-to-date information please go to the ISRCTN link below. |
| Link to record in ISRCTN Register | ISRCTN83107787 |
| Date last extracted from ISRCTN register | 17/04/2008 |
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