Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination With Oseltamivir, in Adults With COVID-19

RA486120

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)

2020-06-15

2022-05-20

2022-09-21

Completed

Early phase I

38

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 Exclusion Criteria: Use of the following concomitant medications is prohibited at Screening Visit and throughout the duration of the trial: 1. Use of Oseltamivir for more than 48 hrs prior to the first treatment dose 2. Use of antiviral drugs (e.g. nucleoside analogue reverse-transcriptase inhibitors, protease inhibitors, etc.) 3. History of long-term or concurrent use of mycophenolate mofetil, methotrexate exceeding 17.5 mg weekly 4. Chloroquine or hydroxychloroquine 5. Any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad as well as uricosuric drugs such as probenecid 6. Treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafinib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib 7. Any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogues 8. Use of rosuvastatin at daily doses higher than 10 mg Medical History of Concomitant Disease Exclusion Criteria * Allergic or hypersensitivity to the IMU-838, Oseltamivir, or any of the ingredients * Pregnant or breastfeeding or with intention to become pregnant during the study * Participants who cannot take trial medication orally at presentation * Undergoing active chemotherapy or radiotherapy. * If the attending clinician believes that there is a specific contra-indication to the IONIC intervention. * Patient has a medical or concomitant disease history preventing them from participating * Critical patients whose expected survival time \< 48-72 hours * Evidence of pancytopenia or immunosuppression * Any contraindication to Oseltamivir or standard of care Presence of the following laboratory values at Screening Exclusion Criteria * Platelet count \<100,000/mm³ (\<100 x 109/L) * Total bilirubin \> 2 x ULN or ALT or GGT \> 5 x ULN * Elevated indirect (unconjugated) bilirubin \>1.2 x ULN (i.e. \>1.1 mg/dL) * Serum uric acid levels at Screening Visit \>1.2 x ULN (for women \>6.8 mg/dL, for men \>8.4 mg/dL) * Renal impairment defined as estimated glomerular filtration rate ≤45 mL/min/1.73m² * Decompensated liver cirrhosis (Child-Pugh score B and C) * History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (New York Heart Association \[NYHA\] class 3 or 4) * Cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA class 4: Cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. * History or presence of any major medical or psychiatric illness (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation, if any of those conditions in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol COVID-19 related exclusion criteria • Participation in any other interventional clinical trial for an experimental treatment for COVID-19

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2023-08-22