E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate COVID-19 |
Умерена инфекция с COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084460 |
E.1.2 | Term | COVID-19 treatment |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 |
The primary objective is to compare the clinical efficacy of XAV-19 to that of placebo in patients with COVID-19 requiring or not oxygen-therapy at inclusion. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - to compare the change in clinical parameters (fever, respiratory rate, shortness of breath, thoracic pain, SpO2, supplemental O2) in patients treated with XAV-19 to that in patients treated with Placebo, - to compare the length of hospital stay of patients treated with XAV-19 to that of patients treated with Placebo, - to compare the viral status of patients treated with XAV-19 to that of patients treated with Placebo, - to compare the safety profile in patients with COVID-19 treated with XAV-19 to that in patients treated with Placebo - to compare overall survival of patients treated with XAV-19 to that of patients treated with Placebo |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I1) Male or female patient aged 18 years or over, weighing >40 Kg and <120 Kg, at the time of signing the informed consent, I2) Patient presenting in a specialized or an emergency unit I3) Patient presenting signs of respiratory disease due to covid-19, evidenced by clinical assessment or imaging AND COVID-19 related symptoms having started less than 10 days prior to screening visit, including at least 2 of the following: fever, cough, sore throat or nasal discharge, dyspnea (shortness of breath), thoracic pain, headache or fatigue, myalgia, anosmia, dysgeusia, diarrhea, nausea I4) Patient with SpO2 > 90% (at ambient air) Patient requiring or not oxygen-therapy (score =4 or 3 on WHO clinical progression 7 point ordinal scale respectively) I5) Patient with a first positive SARS-CoV-2 test (RT-PCR, RT-qPCR or antigen test) in the last 10 days or at screening I6) Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at screening and use a highly effective birth control until 90 days after the administration of study drug I7) Non-vasectomized male patients having a female partner of childbearing potential must agree to use a highly effective method of contraception until 90 days after the administration of study drug I8) Patient capable of giving signed informed consent I9) Patient requiring or not oxygen-therapy (score 2, 3 or 4 on WHO clinical progression 7point ordinal scale respectively) |
|
E.4 | Principal exclusion criteria |
E1) Patient with a positive SARS CoV-2 test (RT-PCR, RT-qPCR or antigen test) of more than 10 days before the screening visit E2) Patient with multiorgan failure E3) Patient requiring immediate Intensive Care Unit (ICU) hospitalization E4) Patient participating in another clinical trial with an investigative agent E5) Pregnancy or breastfeeding E6) Patient with critical respiratory illness meeting one of the following criteria: high flow oxygenation, NIV, invasive mechanical ventilation or ECMO E7) Patient requiring oxygenation at a flow rate > 6L/min E8) Patients presenting any of clinical signs indicative of severe systemic illness, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, or PaO2/FiO2 <300 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. The aggravation is defined as a worsening of the score of at least 1 point on the WHO 7-point ordinal scale compared to the score on the WHO-7 ordinal scale at randomization. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 8 days after treatment. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are: • Proportion of patients with an aggravation of COVID-19 within 8 days after treatment, defined as a worsening of the score of at least 2 points on the WHO clinical progression 7 point ordinal scale compared to the score at randomization • Proportion of patients with an aggravation of COVID-19 within 15 and 29 days after treatment, • Proportion of patients with an improvement, no change, or an aggravation on the WHO-7 ordinal scale at Day 15 compared to the score at Day 8 and at day 29 compared to day 15 • Change in clinical parameters between randomization and Day 3, 5, 8, 15 and 29: fever (>38°C), respiratory rate, SpO2, supplemental O2, • Change in severity, on Common Terminology Criteria of Adverse Events (CTCAE) scale, between randomization and Day 3, 5, 8, 15 and 29: shortness of breath and thoracic pain (See Appendix 12.2), • Duration of patient’s requirement in supplemental O2, • Duration of aggravation • Length of hospital stay, • Clinical status at Day 3,5, 15 and Day 29 using the WHO 7-point ordinal scale for COVID-19, • Viral status: RT-PCR for SARS-CoV-2 (positive/negative) at randomization and on Day 8 or at the end of follow-up, whichever comes first • Viral load (if local practice enables it): RT-qPCR for SARS-CoV-2 at randomization and on Day 8 or at the end of follow-up, whichever comes first • Proportion of patients referred to ICU between randomization and Day 3, 5, 8,15 and 29, • Proportion of patients with need for mechanical ventilation at randomization and at Days 3, 5, 8, 15 and 29, • OS: 8- 15 and 29 -day survival rates, defined by the crude proportion of patients still alive 8, 15 or 29 days after randomization • Safety parameters (i.e. adverse events, hypersensitivity or allergy, white and red blood cells, liver enzymes, creatinine) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between randomization and Day 3, 5, 8, 15 and 29. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Anti-Drug-Antibody (ADA) SARS-Cov-2 neutralizing titers |
|
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) | Yes |
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 | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Viet Nam |
Bulgaria |
Romania |
Spain |
Greece |
Turkey |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of the study will be the last patient’s last visit. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 13 |
E.8.9.2 | In all countries concerned by the trial days | 0 |