| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Chronic Obstructive Pulmonary Disease (COPD). In part 1 of the study the patients are in stable state. In part 2 of the study patients have a respiratory virus infection (i.e. cold or flu virus). |
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| E.1.1.1 | Medical condition in easily understood language |
| COPD is a disease of the airways resulting in breathing difficulties. The most common cause is smoking. |
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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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010953 |
| E.1.2 | Term | COPD exacerbation |
| E.1.2 | System Organ Class | 100000004855 |
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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 |
| We want to see if SNG001 activates antiviral defences in the lungs of people with COPD. We are interested in doing this because COPD patients often suffer badly when they get colds, it seems that the colds really hit their chest. SNG001 is an inhaled form of interferon beta, an antiviral protein we all make when we have a viral infection. Data has shown that interferon beta boosts COPD cell defences in the laboratory. We hope we can boost the lungs defences in COPD patients by delivering SNG001 by inhaler directly into the lungs of patients when they have a confirmed virus infection. We can measure this in sputum (phlegm) during the trial. |
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| E.2.2 | Secondary objectives of the trial |
We will also want to see if lung function and symptoms scores suggest a potential clinical benefit of SNG001. This will help with the design of future trials.
SNG001 has been delivered safely to more than 130 asthma patients before, and it showed some clinical benefit, this is the first time it has been delivered to COPD patients, so we will dose 10 (8 SNG001, 2 placebo) patients when they haven’t got a cold, before moving onto the main part of the study, where 80 patients will be dosed. Thus an important aspect of the trial is the assessment of the safety of SNG001 in COPD patients.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
PART 1
1. Male or female, between and including 40-75 years of age, at the time of the screening visit.
2. A confirmed physician diagnosis of COPD or a medical history consistent with a diagnosis of COPD for at least 12 months prior to the screening visit.
3. Post bronchodilator FEV1/FVC ratio <0.7.
4. Post bronchodilator FEV1 ≥40% of predicted (at screening and post sputum induction pre-dose).
5. Should have stable COPD, having no symptoms of an exacerbation and/or respiratory tract infection currently and/or within the past 6 weeks of screening and/or randomisation.
6. Should be prescribed and taking regularly one or more long acting bronchodilator (e.g. long acting β2 agonist (LABA), long acting muscarinic antagonist [LAMA]) with or without an inhaled corticosteroid maintenance therapies for their COPD.
7. Patients who produce sputum most days.
8. Provide written informed consent.
9. The patient produced an adequate sputum sample at the screening visit.
10. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception. Acceptable birth control methods are stated in the protocol. Women should have been stable on their chosen method of birth control for a minimum of 3 months before entering the trial and should continue with birth control for 1 month after the last dose of inhaled IFN-β-1a/matching placebo. In addition to the acceptable birth control method (except for the practice of total sexual abstinence), condom (in UK with spermicides) should be used by the male partner for sexual intercourse from randomisation (Visit 2) and for 1 month after the last dose of inhaled IFN-β-1a/matching placebo to prevent pregnancy.
Women not of childbearing potential are defined in the protocol.
11. Motivation (in the Investigator’s opinion) to comply with protocol requirements and complete all study visits, including 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 potential benefits).
PART 2
1. Male or female, between and including 40-85 years of age at the time of the consent visit.
2. A confirmed physician diagnosis of COPD or a medical history consistent with a diagnosis of COPD for at least 12 months prior to the consent visit.
3. Post bronchodilator FEV1/FVC ratio <0.7.
4. Post bronchodilator FEV1 ≥30% of predicted.
5. To have had 1 or more COPD exacerbations in the last 12 months requiring intervention with oral corticosteroids and/or antibiotics.
6. Patient reported evidence that a respiratory virus has made their COPD significantly worse in the past.
7. Patients who have chronic bronchitis OR produce sputum on most days.
8. Should be prescribed and taking regularly one or more long acting bronchodilator (e.g. LABA, LAMA) with or without an inhaled corticosteroid mainte nance therapy for their COPD.
9. Patients on self-management plans agree to consult a healthcare professional prior to taking oral corticosteroids or antibiotics for treatment of a COPD exacerbation.
10. Provide written informed consent.
11. Be the owner or user of a mobile phone and be able to and agree to respond to the required SMS messages for the trial.
12. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception. Acceptable birth control methods are stated in the protocol. Women should have been stable on their chosen method of birth control for a minimum of 3 months before entering the trial and should continue with birth control for 1 month after the last dose of inhaled IFN-β-1a/matching placebo. In addition to the acceptable birth control method (except for the practice of total sexual abstinence), condom (in UK with spermicides) should be used by the male partner for sexual intercourse from randomisation (Visit 2) and for 1 month after the last dose of inhaled IFN-β-1a/matching placebo to prevent pregnancy.
Women not of childbearing potential are defined in the protocol.
13. Motivation (in the Investigator’s opinion) to comply with protocol requirements and complete all study visits, including 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 potential benefits).
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| E.4 | Principal exclusion criteria |
PART 1
1. Any condition, including findings in the medical history or in the pre-randomisation assessments that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct or evaluation.
2. Current treatment or treatment within the past 6 weeks with oral corticosteroids or other systemic immunosuppressive.
3. Oxygen saturation of ≤ 92%.
4. Patients who require any form of oxygen therapy or non-invasive ventilation.
5. The patient has received live vaccines in the past six weeks prior to randomisation or attenuated vaccines in the past two weeks prior to randomisation.
6. Current or previous participation in another clinical trial where the patient has received a dose of an investigational medicinal product (IMP) containing small molecules within 12 weeks prior to entry into this study or containing biologicals within 12 months prior to entry into this study.
7. Active interstitial lung disease or past history of lung cancer not considered cured, significant bronchiectasis, cystic fibrosis, alpha1 antitrypsin deficiency or a history of significant chronic asthma.
8. Patients who currently have, or have had within the past 3 months, any significant underlying medical condition(s) that could impact the interpretation of results (see protocol for examples)
9. History of hypersensitivity to natural or recombinant IFN-β or to any of the excipients in the drug preparation.
10. Significant history of depressive disorder or suicidal ideation. Specifically, individuals with current severe depression (see protocol for examples) individuals with a past history of depression that required hospitalisation or referral to psychiatric services in the past 5 years; individuals who currently feel suicidal or have attempted suicide in the past.
11. Patients who are currently receiving anti-epileptic therapy and/or have uncontrolled epilepsy.
12. History of drug or alcohol abuse within 12 months prior to enrolment.
13. Female who is breast-feeding, pregnant or intends to become pregnant.
14. Patients with clinically significant arrhythmias or implantation of permanent pacemaker or implanted cardiac defibrillator
15. Patients with unstable ischaemic heart disease (including, but not limited to, unstable angina, myocardial infarction within the preceding 6 months).
PART 2
1. Any condition, including findings in the medical history or in the pre-study assessments that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct or evaluation.
2. The patient currently has or has had any of the following within the past 6 weeks:
a. A moderate or severe exacerbation of COPD (Appendix A: Exacerbations definitions (GOLD 2017)).
b. An upper or lower respiratory tract infection
Note: there should be at least 6 weeks between the resolution of any of the above and the patient entering the study.
3. Oxygen saturation of ≤92%.
4. Patients who require any form of oxygen therapy.
5. Current or previous participation in another clinical trial where the patient has received a dose of an investigational medicinal product (IMP) containing small molecules within 12 weeks prior to entry into this study or containing biologicals within 12 months prior to entry into this study.
6. Active interstitial lung disease or past history of lung cancer not considered cured, significant bronchiectasis, cystic fibrosis, alpha-1 antitrypsin deficiency or a history of significant chronic asthma.
7. Patients who currently have, or have had within the past 3 months, any significant underlying medical condition(s) that could impact interpretation of results (see protocol for examples)
8. History of hypersensitivity to natural or recombinant IFN-β or to any of the excipients in the drug preparation.
9. Significant history of depressive disorder or suicidal ideation. Specifically, individuals with current severe depression (see protocol for examples) individuals with a past history of depression that required hospitalisation or referral to psychiatric services in the past 5 years; individuals who currently feel suicidal or have attempted suicide in the past.
10. Patients who are currently receiving anti-epileptic therapy and/or have uncontrolled epilepsy.
11. History of drug or alcohol abuse within 12 months prior to enrolment.
12. Patients with clinically significant arrhythmias or implantation of permanent pacemaker or implanted cardiac defibrillator
13. Patients with unstable ischaemic heart disease
14. Female who is breast-feeding, pregnant or intends to become pregnant.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1
The following outcome measures will be used to assess respiratory function, induction of biomarkers and general safety and tolerability as co-primary endpoints of equal importance:
- Forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR).
- Changes in sputum differential cell counts
- Anti-viral IFN-stimulated genes (eg, MXA, 2’-5’ OAS, GBP1, IFIT2, CXCL10) in cells from expectorated sputum
- General safety and tolerability measures including changes in incidence of adverse events, vital signs, ECG readings, haematology, blood chemistry, coagulation and urinalysis.
Part 2
The following outcome measures will be used to assess induction of anti-viral biomarkers, efficacy and general safety and tolerability as co-primary endpoints of equal importance:
- Anti-viral IFN-stimulated genes (eg, MXA, 2’-5’ OAS, GBP1, IFIT2, CXCL10) in cells from expectorated sputum
- CXCL10 in blood samples
- Changes in FEV1 and PEFR during the study period
- Changes in Breathlessness, cough and sputum scale (BCSS) score and time to return to normal symptoms post a moderate exacerbation (Group B only)
- Sputum viral and bacterial load
- Reliever medication usage during the treatment period
- Antibiotic and oral corticosteroid usage during the study period
- General safety and tolerability measures including changes in incidence of adverse events, vital signs, ECG readings, haematology, blood chemistry, coagulation and urinalysis.
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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) |
| There are no secondary endpoints for this study. This is a Phase II exploratory study which aims to both confirm the effect of inhaled SNG001 on the upregulation of IFN-β driven anti-viral biomarkers in conjunction with assessing impact on efficacy and safety measures for COPD patients with and without respiratory viral induced exacerbations. As such, the outcome measures assessed during the study are considered of equal importance to meet the study objectives and are listed as co-primary endpoints in section E5-1. |
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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 | No |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| 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 | Yes |
| 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 | 5 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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