Viral Pneumonia
Conditions
Keywords
Influenza, Respiratory Syncytial Virus, Rhinovirus, Adenovirus, Human Metapneumovirus, Coronavirus, Intubated, Mechanically ventilated, Interferon, Intensive care, SARS-CoV-2, Parainfluenza
Brief summary
The goal of this Phase 2 study is to assess about the safety, antiviral biomarker responses and efficacy of SNG001 when given to patients requiring invasive mechanical ventilation due to a respiratory virus infection. Its ability to speed up virus clearance and reduce mortality, compared with standard of care, will be studied. The study is split into two parts. All participants will receive standard of care in addition to SNG001 or placebo. In Part 1, the safety of SNG001 will be assessed. Participants of 50 years and older will receive study drug or placebo once a day for up to 14 days, whilst in hospital. In Part 2, the primary objective will be the efficacy of SNG001. Participants between 18 and 50 years with an immunocompromising condition and patients over 50 years (with or without an immunocompromising condition) will receive study drug once a day for up to 14 days, whilst in hospital.
Interventions
DRUGSNG001
SNG001 nebuliser solution is presented as a ready-to-use aqueous solution (neutral pH) in glass syringes containing 0.65 mL of drug product solution containing 12 MIU/mL of IFNβ 1a.
DRUGPlacebo
The placebo nebuliser solution is presented in glass syringes containing 0.65 mL of solution containing the same formulation as the study medication but without IFNβ 1a (i.e., only the excipients of the SNG001 solution).
Sponsors
Synairgen Research Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part 1 of this study will include a low-dose (one syringe) first cohort, followed by an optional second cohort utilising a two-syringe dose. Part 2 will commence following the conclusion of Part 1 and will utilise the two-syringe dose. Both Part 1 and Part 2 of the study will be randomised, double-blind and placebo-controlled.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1 Inclusion Criteria: To be eligible for randomisation into Part 1 of this study, each participant must fulfil the following criteria: 1. Informed consent or legal representative's consent obtained. 2. Patients ≥50 years of age at the time of consent. 3. Patient admitted to the ICU and requiring invasive mechanical ventilation (IMV) due to a respiratory virus infection. 4. Presence of Influenza A (Flu A), Influenza B (Flu B), respiratory syncytial virus (RSV), rhinovirus (RV), adenovirus, parainfluenza, human metapneumovirus (HMPV), or coronaviruses (including SARS-COV-2 and seasonal coronaviruses) in a nose swab sample, confirmed by a positive virus test using a Sponsor approved rapid POC test (e.g., reverse transcription polymerase chain reaction \[RT-PCR\]). 5. Time from intubation to administration of first dose of study medication ≤48 hours. 6. Women of childbearing potential must have a negative pregnancy test. For this study, women of childbearing potential are defined as women \<55 years old. Part 1
Exclusion criteria
A participant must not be randomised into Part 1 of the study if they meet any of the following criteria: 1. Expected termination of IMV within 24 hours from the time of randomisation 2. Life expectancy \<24 hours. 3. Liver failure (Child-Pugh C). 4. Severe congestive heart failure (New York Heart Association \[NYHA\] IV). 5. Receipt of lung transplant. 6. Known or suspected active tuberculosis, or infection with other mycobacteria 7. Known or suspected active systemic fungal infection. 8. Anticipated transfer to another hospital which would prevent the participant from continuing in the study and completing protocol assessments. 9. Need for long-term mechanical ventilation prior to ICU admission. 10. Use of inhaled sedation. 11. Presence of tracheostomy or laryngectomy. 12. Requirement for airway pressure release ventilation mode. 13. History of hypersensitivity to natural or recombinant IFNβ or to any of the excipients in the drug preparation. 14. Any condition, including findings in the patient's medical history or in the pre-randomisation study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation. 15. Participation in previous clinical studies of SNG001. 16. Current or previous participation in another clinical study where the participant has received a dose of an Investigational Medicinal Product (IMP) containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study. 17. Known or suspected pregnancy. 18. Females who are breast-feeding or lactating. 19. Immunocompromising condition, including: * Established acquired immune deficiency syndrome (AIDS) defined as a cluster of differentiation 4 (CD4) count \<200 cells/microL, and/or the presence of any AIDS-defining condition; * Haematological malignancy; * Bone marrow transplantation; or * Immunosuppressive therapy, including: * Cancer therapy (e.g. chemo-, radio-, immuno-, hormone or other types of therapy), immune-cell depleting therapy, immunosuppressive therapy for autoimmune disorders, medications for prevention of organ transplantation rejection, administered within 6 months prior to randomisation; or * Corticosteroids \>20 mg of prednisone or equivalent per day administered continuously for \>14 days prior to randomisation. 20. Severe chronic lung disease requiring home oxygen therapy, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis. Part 2 Inclusion Criteria: To be eligible for randomisation into Part 2 of this study, each participant must fulfil the following criteria: 1.a Patients ≥18 and \<50 years of age at the time of consent, with an immunocompromising condition, including: * Solid tumour malignancy undergoing cancer therapy (e.g. chemo-, radio-, immuno-, hormone or other types of therapy); * Haematological malignancy in remission, with or without maintenance therapy; * Immunosuppressive therapy for autoimmune disease; * Therapy for prevention of organ transplant rejection; * Corticosteroids \>20 mg of prednisone or equivalent per day, administered continuously for \>14 days prior to randomisation or 1. b Patients ≥50 years of age at the time of consent, with or without an immunocompromising condition (as defined above). 2. Patient admitted to the ICU and requiring IMV due to a respiratory virus infection. 3. Presence of Flu A, Flu B, RSV, RV, adenovirus, parainfluenza, HMPV, or coronaviruses (including SARS-COV-2 and seasonal coronaviruses) in a Lower Respiratory Tract sample, confirmed by a positive virus test using a Sponsor approved rapid POC test (e.g., RT-PCR). 4. Time from intubation to administration of first dose of study medication ≤48 hours. 5. Informed consent or legal representative's consent obtained. 6. Women of childbearing potential must have a negative pregnancy test. For this study, women of childbearing potential are defined as women \<55 years old. Part 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: AE and SAE Severity | Up to 28 days from randomisation | The occurrence and severity of AEs and serious adverse events (SAEs), including pre-specified respiratory and cardiovascular deteriorations. |
| Part 2: All-cause mortality | Within 28 days from randomisation | All deaths recorded on study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Change in mSOFA from baseline | Up to 14 days | Change from baseline in modified Sequential Organ Failure Assessment (mSOFA) score during ICU (intensive Care Unit) stay. |
| Part 2: Time to Extubation | Up to 28 days from randomisation | Time to extubation. |
| Part 2: Number of ventilator free days | Up to 28 days from randomisation | Ventilator-free days over 28 days from randomisation |
| Part 2: Duration of stay in ICU | Up to 28 days from randomisation | Duration of ICU stay. |
| Part 2: Duration of stay in hospital | Up to 28 days from randomisation | Duration of hospital stay. |
| Part 2: Time to first negative virus test | Up to 14 days from randomisation | Time to first negative virus test in tracheal aspirates. |
| Part 2: Change in IFNβ levels from baseline | Up to 14 days from randomisation | Change from baseline in levels of IFNβ dependent biomarkers in tracheal aspirates |
| Part 2: No organ support | At 28 days from randomisation and at 28 days post final dose | Alive and free of organ support |
| Part 2: All Cause Mortality | Within 28 days post final dose | All deaths recorded post final dose |
| Part 2: Change in OSCI from baseline | Up to 28 days from randomisation | Change in Ordinal Scale for Clinical Improvement (OSCI) score from baseline to 7, 10, 14 and 28 days post randomisation. |
| Part 2: AE and SAE severity | Up to 42 days from randomisation | The occurrence and severity of AEs and SAEs, including pre-specified respiratory and cardiovascular deteriorations. |
Countries
Belgium, France, Netherlands, Spain, United Kingdom, United States
Contacts
Primary ContactSophie Hemmings
Outcome results
None listed