Comparing Efficacy and Safety of Inhaled SNG001 to Placebo

• ClinicalTrials.gov Identifier: NCT01126177
• Recruitment Status: Completed
• First Posted: May 19, 2010
• Last Update Posted: February 13, 2012
• Sponsor: Synairgen Research Ltd.
• Information provided by (Responsible Party): Synairgen Research Ltd.

Tracking Information

• First Submitted Date: May 17, 2010
• First Posted Date: May 19, 2010
• Last Update Posted Date: February 13, 2012
• Study Start Date: March 2010
• Actual Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2012)

S-ACQ [ Time Frame: Baseline - Day 8 ]

To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the modified intention to treat (mITT) population as measured by change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire (symptoms plus short-acting β2 agonist. - change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire

Original Primary Outcome Measures (submitted: May 18, 2010)

To evaluate the superiority of inhaled SNG001 compared to placebo [ Time Frame: Day 1-28 ]

To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the modified intention to treat (mITT) population as measured by:

• peak score of the Asthma Index
• change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire

Current Secondary Outcome Measures (submitted: February 3, 2012)

• Asthma Index [ Time Frame: Day 1-14 ]
  To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the mITT population as measured by peak score of the Asthma Index (Sorkness et al, 2008) in the 14 day period following first administration of study drug (measured from 24 hours post first dose to 24 hours post last dose taken).
• S-ACQ [ Time Frame: Baseline - Day 8 ]
  To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the per protocol (PP) population as measured by change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire.
• Asthma Index [ Time Frame: 14 days ]
  To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the PP population as measured by peak score of the Asthma Index in the 14 day period following first administration of study drug (measured from 24 hours post first dose to 24 hours post last dose taken).
• Sever Exacerbation [ Time Frame: Day 1-14 ]
  To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses as measured by the proportion of subjects experiencing a severe exacerbation (Appendix 2) in the mITT population during the 14 days following first administration of study drug.
• Lung Function [ Time Frame: Day 1-14 ]
  To compare inhaled SNG001 to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of decreases in lung function (AUC FEV1 and PEFR) caused by respiratory viruses in the mITT population during the 14 day dosing period.
• Viral Load [ Time Frame: Days 4 and 7 ]
  To compare the effect of inhaled SNG001 to placebo when administered to asthmatic subjects on viral load on Days 4 and 7 in sputum.
• Safety [ Time Frame: Day 1-14 ]
  To evaluate the safety of inhaled SNG001 when administered to asthmatic subjects.
• Concomitant Medications [ Time Frame: Day 1-28 ]
  To compare the frequency of use of concomitant medications in relation to conditions of the respiratory tract during the study Treatment Phase in asthmatic subjects receiving inhaled SNG001 compared to placebo.
• Pharmacokinetic [ Time Frame: Day 1-14 ]
  To gain information on the pharmacokinetic profile of inhaled SNG001 administered to asthmatic subjects during a respiratory virus infection.
• Pharmacodynamic [ Time Frame: Day 1-14 ]
  To gain information on the pharmacodynamic profile of inhaled SNG001 administered to asthmatic subjects during a respiratory virus infection.

Original Secondary Outcome Measures (submitted: May 18, 2010)

• To evaluate the superiority of inhaled SNG001 compared to placebo [ Time Frame: Day 1-28 ]
  To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the per protocol (PP) population as measured by:

  • peak score of the Asthma Index
  • change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire.
• To evaluate the superiority of inhaled SNG001 compared to placebo [ Time Frame: 14 days ]
  To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses as measured by the proportion of subjects experiencing a severe exacerbation in the mITT population during the 14 days following first administration of study drug.
• To compare inhaled SNG001 to placebo [ Time Frame: 14 days ]
  To compare inhaled SNG001 to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of decreases in lung function (AUC FEV1 and PEFR) caused by respiratory viruses in the mITT population during the 14 day dosing period.
• To compare the effect of inhaled SNG001 to placebo when administered to asthmatic subjects in the reduction of viral load on Days 4 and 7 in sputum. [ Time Frame: Day 4-7 ]
• To evaluate the safety of inhaled SNG001 when administered to asthmatic subjects. [ Time Frame: Day 1-28 ]
• To compare the frequency of use of concomitant medications in relation to conditions of the respiratory tract during the study Treatment Phase in asthmatic subjects. [ Time Frame: Day 1-28 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparing Efficacy and Safety of Inhaled SNG001 to Placebo
• Official Title: A Randomised, Double-blind, Placebo-controlled Phase II Study, Comparing the Efficacy and Safety of Inhaled SNG001 to Placebo Administered to Asthmatic Subjects After the Onset of a Respiratory Viral Infection for the Prevention or Attenuation of Asthma Symptoms Caused by Respiratory Viruses

Brief Summary

When people with asthma get respiratory virus such as a cold or flu it often increases asthma symptoms. The investigators will test the study medication to find out if it can prevent the virus spreading from the nose to the lungs.

SNG001 contains Interferon-beta that occurs naturally in the body. In this study, SNG001 will be given by a nebuliser.

• Detailed Description: The study will consist of a Pre-Treatment Phase into which subjects potentially eligible for the Treatment Phase will be recruited. Subjects will remain in the Pre-Treatment Phase until they experience respiratory virus symptoms at which time they will be further screened for eligibility for entry into the Treatment Phase. If eligible, subjects will be randomised 1:1 to receive SNG001 or placebo once daily for 14 days. Doses will be delivered by a CE marked breath actuated nebuliser (I-neb Philips Respironics). Subjects will be assessed for changes in changes in respiratory virus symptoms and asthma symptoms at home using a text message system, and via telephone questionnaire. Lung function will be measured both at home by the subjects (PEFR only) and in the clinic. Efficacy and safety will be monitored until at least 30 days post treatment.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Asthma

Intervention

• Drug: Interferon beta 1a
  SNG001, IFN-β1a solution for inhalation
• Drug: Placebo
  Placebo (excipients of the SNG001 solution only)

Study Arms

• Placebo Comparator: Placebo
  Placebo once daily for 14 days
  Intervention: Drug: Placebo
• Experimental: SNG001
  Intervention: Drug: Interferon beta 1a

• Publications *: Djukanović R, Harrison T, Johnston SL, Gabbay F, Wark P, Thomson NC, Niven R, Singh D, Reddel HK, Davies DE, Marsden R, Boxall C, Dudley S, Plagnol V, Holgate ST, Monk P; INTERCIA Study Group. The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial. Am J Respir Crit Care Med. 2014 Jul 15;190(2):145-54. doi: 10.1164/rccm.201312-2235OC.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 18, 2010): 300
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2012
• Actual Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

1. Male or female aged 18 to 65 years of age at the time of screening.

2. Symptoms of asthma for at least 2 years pri or to the Screening Visit, confirmed by a medical history and:

   1. ≥12% and 200mL bronchodilator reversibility at screening or documented in the past, OR,
   2. evidence of bronchial hyper-responsiveness at screening or documented in the past, OR,
   3. a documented hospital admission (including an Accident and Emergency admission) for asthma since the age of 18, OR.
   4. documented evidence that they have attended their GP surgery, out-of-hours clinic (or alternative health care provider) for worsening of asthma symptoms, since the age of 18
3. Must answer "Yes" to the question "Does a cold make your asthma worse?"
4. To have had at least one asthma exacerbation suspected to have been caused by a respiratory virus in the last 24 months which required the use of oral steroids and/or additional treatment with antibiotics on one or more occasion.
5. Must be taking regular inhaled corticosteroids.
6. Pre-bronchodilator FEV1 ≥ 40 % predicted at screening.
7. Post-bronchodilator FEV1 ≥ 50 % predicted at screening.
8. Provide written informed consent.
9. Females of childbearing potential must be using a medically acceptable adequate form of birth control and agree to maintain this usage throughout the duration of and four weeks post the Treatment Phase of the study.
10. Motivation (in the Investigator"s opinion) 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01126177
• Other Study ID Numbers: SG005
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Synairgen Research Ltd.
• Study Sponsor: Synairgen Research Ltd.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ratko Djukanovic, MD, DM, FRCP; University of Southampton

• PRS Account: Synairgen Research Ltd.
• Verification Date: February 2012