COVID-19 MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: VIDOFLUDIMUS CALCIUM
Product Code: IMU-838
Pharmaceutical Form: Tablet
INN or Proposed INN: Vidofludimus calcium
CAS Number: 1354012-90-0
Current Sponsor code: IMU-838
Other descriptive
Sponsors
Immunic AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients at least 18 years old (may only be extended to include children 12 years or older after MA1 following approvals of a Protocol Amendment) 2. Admitted to the hospital or other medical in-patient treatment facility for treatment of COVID-19 The hospitalization needs to be for medical reasons (treatment of COVID-19 disease) and cannot be for social reasons or due to housing insecurity. 3. SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) test in a nasopharyngeal, oropharyngeal or respiratory sample at =4 days before randomization 4. Moderate COVID-19 disease defined as fulfilling clinical status category 3 or 4 on the WHO 9-point ordinal scale [21]: o Category 3: Hospitalized (see note above for US only), virus-positive, no oxygen therapy with the following conditions: - The hospitalization needs to be for medical reasons (treatment of COVID-19 disease) and cannot be for social reasons or due to housing insecurity o Category 4: Hospitalized, virus-positive, oxygen by mask or nasal prongs (excluding high-flow oxygen therapy) with the following conditions: - Peripheral capillary oxyhemoglobin saturation (SpO2) >92% at maximum of 6 liters oxygen flow per minute - Stable respiratory rate =30 breaths/min at maximum of 6 liters oxygen flow per minute 5. Presence of at least 1 symptom characteristic for COVID-19 disease i.e., fever, cough or respiratory distress 6. Willingness and ability to comply with the protocol 7. Written informed consent given prior to any trial-related procedure 8. For women of childbearing potential: Application of a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly) together with a barrier method between trial consent and 30 days after the last intake of the IMP. Highly effective forms of birth control are those with a failure rate less than 1% per year and include: o oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation o oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation o intrauterine device or intrauterine hormone-releasing system o bilateral tubal occlusion o vasectomized partner (i.e., the patient’s male partner underwent effective surgical sterilization before the female patient entered the clinical trial and is the sole sexual partner of the female patient during the clinical trial) o sexual abstinence (acceptable only if it is the patient’s usual form of birth control/lifestyle choice; periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are no acceptable methods of contraception) Barrier methods of contraception include: o Condom o Occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository 9. Male patients must agree not to father a child or to donate sperm starting at Screening, throughout the clinical trial and for 30 days after the last intake of the IMP. Male patients must also o abstain from sexual intercourse with a female partner (acceptable only if it is the patient’s usual form of birth control/lifestyle choice), or o use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and o if they have a female partner of childbearing potential, the partner should use a highly effe
Exclusion criteria
Exclusion criteria: Underlying disease-related exclusion criteria 1. Involvement in the trial is not in the patient’s best interest according to the investigator’s decision, including the presence of any condition that would, in the assessment of the investigator, not allow the protocol to be followed safely 2. Presence of respiratory failure, shock, and/or combined failure of other organs that requires ICU monitoring in the near foreseeable future 3. Critical patients whose expected survival time 2 x ULN o Alanine aminotransferase (ALT) or gamma glutamyl transferase (GGT) >5 x ULN 5. Participation in any other interventional clinical trial 6. Hospitalization primarily for reasons other than COVID-19 (including primarily for concomitant conditions during ongoing SARS-CoV-2 infection) 7. Anticipated transport to a different hospital or institution, in particular when such transport is anticipated for pending ECMO or RRT treatment 8. Clinical suspicion of a bacterial superinfection at Screening IMP-related exclusion criteria 9. Patients who cannot take drugs orally 10. Allergic or hypersensitive to the IMP or any of the ingredients 11. Use of the following concomitant medications is prohibited from Screening to end of treatment with IMP in this trial (up to Day 14) if not indicated otherwise in this protocol: o Concurrent use of any mycophenolate mofetil or of methotrexate exceeding 17.5 mg weekly o Any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad (Zurampic™) as well as uricosuric drugs such as probenecid o Current treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafenib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib o Any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogs o Use of rosuvastatin at daily doses higher than 10 mg o Arbidol and Colchicine o Any use of other DHODH inhibitors, including including teriflunomide (Aubagio™) or leflunomide (Arava™) o Chloroquine and Hydroxychloroquine during the entire trial, unless taken for indicated use before entering the trial. 12. Patients with clinically relevant conditions leading to hyperuricemia. 13. Use of any investigational product within 8 weeks or 5x the respective half-life before the date of informed consent, whichever is longer, and throughout the duration of the trial General exclusion criteria 14. Patients who have a “do not intubate” or “do not resuscitate” order (unless the patient waives in writing this order and will allow intubation for the duration of the trial period) 15. Patients with pre-existing end-stage liver disease (Child Pugh B and C score) 16. Patients with known Gilbert syndrome (unless their indirect [unconjugated] bilirubin level is confirmed to be <1.2 x ULN, i.e. <1.1 mg/dL) 17. Patients with known acute or clinically relevant chronic renal failure, patients currently on dialysis, as well as patients with an estimated glomerular filtration rate value <30 ml/min/1.73 m2 body surface area according to the Chronic Kidney Disease Epidemiology Collaboration equation for adults ( or the Schwartz bedside equation for children and adolescents, if applicable) 18. History or presence of serious or acute heart disease such as uncontrolled cardiac dysr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of IMU-838 plus investigator’s choice of standard of care therapy (SoC) vs placebo plus SoC in the treatment of coronavirus disease 2019 (COVID-19) based on the need for invasive ventilation (INV) up to 28 days;Secondary Objective: - To evaluate the efficacy of IMU-838 (+SoC) vs placebo (+SoC) in the treatment of COVID-19 based on survival without respiratory failure, the duration of hospitalization in intensive care unit (ICU) and all-cause mortality up to 28 days - To evaluate the efficacy of IMU-838 (+SoC) vs placebo (+SoC) in the treatment of COVID-19 based on a variety of further variables and time points (e.g., clinical status, renal impairment, oxygenation, hospitalization, concomitant vasoactive treatments, clinical recovery) - To evaluate trough plasma levels of IMU-838 - To evaluate safety and tolerability of IMU-838 - To explore blood levels of disease markers - To explore viral titers, measures of viral virulence and inflammatory markers;Primary end point(s): Proportion of patients without any need for INV until end-of-study (EoS);Timepoint(s) of evaluation of this end point: Day 0 to day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Day 0 to day 28;Secondary end point(s): • Proportion of patients surviving without respiratory failure (defined as any need of ICU.INV. high-flow oxygen or extracorporeal membrane oxygenation (ECMO*) until EoS) • Duration of ICU treatment until EoS • 28-day all-cause mortality • Time to clinical improvement, defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9-category ordinal scale1, or live discharge from hospital without oxygen supplementation, whichever comes first • Duration of hospitalization • Proportion of patients: - free of renal-replacement therapy (RRT)* until EoS - free of ECMO* until EoS • Proportion of patients - free of INV until Days 6 and 14* - free of RRT until Days 6 and 14* - free of ECMO until Days 6 and 14* - with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 - with auxiliary oxygen therapy* (including all types of oxygen therapy) until Days 6, 14, and 28 • with clinical recovery defined as: -Axillary temperature /=98% without oxygen inhalation - With clinical improvement, defined as an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first • Change in daily clinical patient status on the WHO 9-category ordinal scale1 • Duration of INV • Duration of ECMO • Duration of RRT • Duration of auxiliary oxygen therapy (including all types of oxygen therapy) • Duration of hospitalization for survivors • The rate of ICU* admission on Days 6, 14, and 28 • Hospital-free days • Time from IMP treatment initiation to death • Time to first prescription of INV • Time to first prescription of RRT • Time to first prescription of ECMO • Time to first prescription of INV, RRT, and ECMO • Time to ICU admission • Cumulative dose of vasoactive therapies (daily until Day 14) and | — |
Countries
Bosnia and Herzegovina, Bulgaria, Germany, Greece, Hungary, Macedonia, the former Yugoslav Republic of, Moldova, Republic of, Romania, Russian Federation, Ukraine, United States
Contacts
Public ContactChief Medical Officer
Immunic AG
Outcome results
None listed