COVID-19 Virus Infection
Conditions
Brief summary
Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. Since two clinical stages of COVID-19 are emerging, an early one with typical clinical characteristics of a viral infection (fever, malaise, cough) and a later one with pneumonia leading to progressive respiratory failure, associated with heavy, cytokine-mediated, inflammation, an intervention by a compound possessing both antiviral activity and immunomodulatory effects would be most effective at the earliest possible stage. The purpose of this clinical trial is to test the efficacy of Interferon-β-1a (IFNβ-1a), in COVID-19 patients in an open label, randomized clinical trial. The design of the study is to test IFNβ-1a in addition to standard of care compared with standard of care alone. The primary outcome is the time to negative conversion of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) nasopharyngeal swabs.
Interventions
DRUGInterferon-ß-1a
IFNβ-1a will be administered subcutaneously at a dose of 44 mcg (equivalent to 12 million international units), three times per week at least 48 hours apart, for a total of two weeks. All patients will receive a total dose of 264 mcg (72 million international units) under physician control
COMBINATION_PRODUCTStandard of Care (SOC)
Any pharmacological (e.g. antibiotics, etc.) and non-pharmacological (e.g. oxygen, ventilation, etc.) treatments prescribed on clinical grounds
Sponsors
Emanuele Bosi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an interventional, monocentric, phase 2, randomized (2:1), open label, controlled clinical study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Informed consent signed 2. Patients hospitalized with confirmed swab RT-PCR detection of SARS-CoV-2 3. X-ray and/or CT diagnosed pneumonia 4. Age \>=18 years 5. Clinical status defined as 3, 4 or 5 on the 7-point ordinal scale
Exclusion criteria
1. Known allergy or hypersensitivity to IFNß-1a or IFNß-1b 2. Presence of severe concomitant illnesses/medical conditions that in the physician opinion do not allow participation to the study 3. Pregnant or lactating females 4. History of major depression disorder or suicidal attempt or suicidal ideation 5. Spontaneous blood alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels \> 5 times the upper limit of normal 6. Clinical status defined as 1, 2, or 6 on the 7-point ordinal scale
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to negative conversion of SARS-CoV-2 nasopharyngeal swab | From baseline to day 29 | Viral load will be measured by Real Time-Polymerase Chain Reaction (RT-PCR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator free days in the first 28 days | From baseline to day 29 | — |
| Changes from baseline in pulmonary computed tomography (CT) imaging severity score | Baseline, day 21; extra follow up at 90 days | Measured with artificial intelligence and expressed as cc and percent values of diseased lung (lung consolidation, ground glass opacities and disease free) |
| Duration of hospital stay expressed in days | From baseline to day 29 | — |
| Viral load measured on plasma with RT-PCR | Baseline, days 3, 5, 7, 9, 11, 13, 15, 21, 29 | — |
| Improvement in clinical severity score (a) | Baseline, days 7, 15, 21, 29 | Defined as percentage of patients reporting each severity rating on a 7-point ordinal scale |
| Improvement in clinical severity score (b) | Baseline, days 7, 15, 21, 29 | Defined as the time to clinical improvement of two points from the time of randomization on a 7-category ordinal scale or live discharge from the hospital, whichever comes first |
| Incidence of new oxygen use, non-invasive ventilation, or high flow oxygen devices during the trial | From baseline to day 29 | — |
| Oxygenation free days in the first 28 days | From baseline to day 29 | — |
| Incidence of new mechanical ventilation use during the trial | From baseline to day 29 | — |
| Number of patients transferred to Intensive Care Unit (ICU) | From baseline to day 29 | — |
| Mortality rate | From baseline to day 29 | — |
Other
| Measure | Time frame |
|---|---|
| Antibodies to IFN-β1a | Baseline, days 7, 15, 29 |
| Plasma and peripheral blood mononuclear cell messenger-RNA (mRNA) expression profile of interferon stimulated genes (ISG) | Baseline, day 15 |
| Antibodies to SARS-CoV-2 | Baseline, days 7, 15, 29 |
Countries
Italy
Outcome results
None listed