E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus Disease (COVID-19) |
|
E.1.1.1 | Medical condition in easily understood language |
Coronavirus Disease (COVID-19) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084401 |
E.1.2 | Term | COVID-19 respiratory infection |
E.1.2 | System Organ Class | 100000004862 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to evaluate the efficacy and tolerability of rabeximod in the treatment of patients with moderate Covid-19. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to provide written informed consent prior to performing study procedures 2. SARS-CoV-2 positivity of the nasal-/throat-swab/saliva swab by reverse-transcriptase-polymerase chain- reaction (RT-PCR) assay tested by the local diagnostic laboratory ≤ 4 days before randomization 3. Moderate severity of COVID -19 (See Appendix 2, FDA severity categorization) 4. Currently hospitalized or requiring hospitalization for the COVID-19 medical care 5. Age >18 and <85 years 6. Presence of at least 3 of the following symptoms as present: fever, cough, myalgia, fatigue 7. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93%, heart rate ≥ 90 beats per minute ≤ 2 days before screening 8. Agree to use an acceptable method of contraception for the duration of the study or not be of childbearing potential. Acceptable methods of birth control include: spermicide with barrier, oral, transdermal, injectable, or implantable contraception, IUD, abstinence, and surgical sterilization of partner. Female subjects are not of childbearing potential if they have had a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or are post-menopausal by at least 12 months.
|
|
E.4 | Principal exclusion criteria |
1. Pregnant, or intend to become pregnant or breastfeed during the study. 2. Patients who are unable to swallow the capsule. 3. Require invasive mechanical ventilation, including extracorporeal membrane oxygenation (ECMO) at study entry. 4. Receiving cytotoxic or biologic treatments (such as tumor necrosis factor (TNF) inhibitors, anti-interleukin-1 (IL-1), anti-IL-6 (tocilizumab or sarilumab), T-cell or B-cell targeted therapies (rituximab), interferon, or Janus kinase (JAK) inhibitors for any indication at study entry. A washout period 4 weeks (or 5 half-lives, whichever is longer) is required prior to screening. 5. Ever received convalescent plasma or intravenous immunoglobulin (IVIg) for COVID-19. 6. Have received high dose corticosteroids at doses >20 mg per day (or prednisone equivalent) administered for ≥14 consecutive days in the month prior to study entry. 7. Have diagnosis of primary tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required). 8. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product. 9. Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study. Use of non-live (inactivated) vaccinations is allowed 10. Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product. 11. Have a history of venous thromboembolism (VTE) (deep vein thrombosis (DVT) and pulmonary embolism (PE) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE). 12. Anticipated discharge from the hospital, or transfer to another hospital (or another unit), which is not a study site within 72 hours after study entry. 13. Have neutropenia (absolute neutrophil count <1000 cells/mLµL). 14. Have lymphopenia (absolute lymphocyte count <200 cells/mLµL). 15. Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x ULN. 16. Have total bilirubin > 1.5 x upper limit of normal. 17. Estimated glomerular filtration rate (eGFR) <30 milliliter/minute/1.73 m2. 18. Have a known hypersensitivity to rabeximod or any of its excipients. 19. Are currently enrolled in any other clinical study involving an investigation product or any other type of medical research judged not to be scientifically or medically compatible with this study. The participant should not be enrolled (start) in another clinical trial for the treatment of COVID-19 or SARS CoV-2 through Day 28. 20. Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®. 21. Are unlikely to survive for at least 48 hours after screening in the opinion of the investigator
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects alive and free of respiratory failure (need for invasive mechanical ventilation, non-invasive ventilation, high-flow nasal cannula oxygen, or ECMO) at Day 28. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1.Response to treatment is defined as the reduction of at least one severity level on the World Health Organization Ordinal Scale for Clinical Improvement (WHO-OSCI). The WHO-OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19 (please see Appendix 1). This will be a continuous outcome defined by the amount of time between randomization to the first response, it will be treated as a time-to-event with possible censoring. 2. To evaluate the impact of rabeximod on the clinical, laboratory, respiratory parameters and viral load, the following clinical and respiratory parameters will be assessed: • ICU admission rate. The percentage of patients admitted to the ICU in the rabeximod group as compared with controls (Time frame: Day 60) • Discharge rate. The percentage of patients discharged in the rabeximod group as compared with controls. (Time frame: Day 28) • Duration (cumulative days) of mechanical ventilation (Time frame: Day 60) • Duration (cumulative days) of extracorporeal membrane oxygenation (Time frame: Day 60) • Duration (cumulative days) of supplemental oxygenation (Time frame: Day 60) • Time to SARS-CoV-2 RT-PCR negativity in upper respiratory tract specimens (Time frame: Day 28) • Change (reduction) in SARS-CoV-2 viral load in upper respiratory tract specimens as assessed by area under viral load curve (Time frame: Day 28 compared to baseline) • Mortality rate at Day 7, Day 14, Day 28, Day 60 • To assess the safety of rabeximod combined with standard of care therapy in terms of serious or non-serious adverse events incidence rate. All adverse event recording.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
at Day 7, Day 14, Day 28, Day 60 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Bulgaria |
Hungary |
Poland |
Romania |
Slovakia |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |