Covid 19
Conditions
Brief summary
To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) and standard care vs. Oseltamivir and standard care in adult subjects with coronavirus disease (COVID-19)
Detailed description
The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) \[IONIC Intervention\] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. At present, there are no known treatments for COVID-19. Whilst, the anticipated scale of the epidemic is such that hospitals, and particularly intensive care facilities, may be massively overstretched. As described by a few models of pandemic spread, up to 50% of the adult population may fall sick over a period of 8-12 weeks, of whom around 10% may require hospitalisation. This figure could imply nearly 2 million hospital admissions. Considering this scenario, therapies which may only have a moderate impact on survival or on hospital resources could be worthwhile. Critically, the present trial design has been developed with consideration of the front-line hospital staff working within an overstretched care system in these unprecedented times. To minimise their burden the protocol is deliberately flexible so that it is suitable for a wide range of settings, allowing: * a broad range of patients to be enrolled (patient pathway, disease stage or mode of diagnosis) * Additional sub-studies may be added to provide more detailed information on side effects or sub-categorisation of patient types but these are not the primary objective and are not required for participation. * To be able to include more sites: the investigators will initiate the trial as a single centre (UHCW) and more sites invited to participate according to the emerging evidence * The investigator have included 'Exploratory and Secondary objectives' in the protocol however, in consideration of the circumstances the research activities will emulate investigations performed as per standard care/routines care to minimise any burden on the delivery teams. This is a Phase 2b, randomised, parallel-group, open-label study to assess the efficacy and safety of an oral dose of IMU-838 (22.5 mg twice daily \[45 mg/day\]) plus Oseltamivir (75mg twice daily \[150mg/day\]) (IONIC Intervetion) or Oseltamivir alone (75mg twice daily) in hospitalised patients with COVID-19.
Interventions
DRUGIMU-838
IMU-838 twice daily at 22.5mg doses for 14 days
DRUGOseltamivir
Oseltamivir twice daily at 75mg doses for 14 days
Sponsors
Immunic AG
University of Warwick
MODEPHARMA
University Hospitals Coventry and Warwickshire NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, Randomized, Parallel-Group, Open-Label Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Male or non-pregnant female patients at least 18 years old 2. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection, either: * Confirmed cases: prospective participants who test positive to a validated specific SARS-CoV-2 nucleic acid test or has the virus identified by electron microscopy or viral culture, as per local trust policy ≤ 7 days before randomisation. * Probable/Suspected case: prospective participants who may have been in contact with a confirmed case of COVID-19, AND have mild to severe COVID-19 clinical symptoms AND radio-graphic evidence\* of pulmonary infiltrates consistent with COVID-19 disease 3. Moderate to severe COVID-19 requiring hospitalisation defined as: a) Clinical status category 3-5 (inclusive) on the 7-point clinical status category scale as proposed by the World Health Organisation (WHO) master protocol: I. Category 3: hospitalized, no oxygen therapy II. Category 4: hospitalized, oxygen by mask or nasal prongs III. Category 5: hospitalized, non-invasive ventilation or high-flow oxygen \*where routinely available, no tests will be requested for research purpose
Exclusion criteria
Therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate whether time-to-improvement is significantly better in IMU-838 plus Oseltamivir (IONIC Intervention) vs. Oseltamivir alone in adult subjects with COVID-19 | 14 days | Time-to-clinical improvement; defined as the time from randomisation to a 2-point improvement on the world health organizations 9-point ordinal scale (ranging from 0-8; 0 being no evidence of clinical infection and 8 being death), discharge from hospital, or death (whichever occurs first) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate safety (number of adverse events) and tolerability (laboratory abnormalities) of IMU 838 + Oseltamivir vs. Oseltamivir alone in adult subjects with COVID-19. | 28 days | Incidence of Adverse events (AEs) and serious adverse events (SAEs), including COVID-19 worsening and incidence of laboratory abnormalities (defined as a 1.5x increase in liver function test results (total protein, albumin, bilirubin, alkaline phosphotase and ALT) from screening). |
| To determine the effects of IONIC Intervention on improvement of at least two points in clinical status scale (from 0 to 8; with 8 being no evidence of clinical infection and 8 being death) | 28 days | Proportion of patients with two-point change on WHO ordinal scale at Day 7 and 28 |
| To assess the effects of IONIC Intervention vs. Oseltamivir on the need for invasive ventilation, renal replacement therapy or ECMO | 14 days | Proportion of patients free of invasive ventilation, renal replacement therapy or ECMO at Day 7 and 14 |
| To assess the effects of IONIC Intervention vs. Oseltamivir on the length of hospital and intensive care unit (ICU) stay | 28 days | To assess the effects of IONIC Intervention vs. Oseltamivir on the length of hospital and intensive care unit (ICU) stay |
| To assess the effects of IONIC Intervention vs. Oseltamivir on the time from treatment initiation to death | 28 days | Mortality at day 28 and time from treatment initiation to death |
Countries
United Kingdom
Outcome results
None listed