| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hospitalized Moderate and Severe COVID-19 Patients |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10021881 |
| E.1.2 | Term | Infections and infestations |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| 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 objective of the study is to evaluate the safety and efficacy of a combination of masitinib and isoquercetin in adult hospitalized patients with moderate and severe COVID-19
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| E.2.2 | Secondary objectives of the trial |
| Secondary objectives are to assess the safety and efficacy of the combination of Masitinib and Isoquercetin in the patients under study by evaluating various parameters related to clinical status. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen ≤72h prior to randomization.
2. Hospitalized patients for the treatment of COVID pneumopathy
3. Patients not requiring invasive intubation at admission with moderate and severe pneumopathy according to the 7-point ordinal scale i.e. 1. Not hospitalized, no limitations on activities; 2.Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
Moderate cases (3, and 4 ; 7-point ordinal scale) i.e. cases meeting all of the following criteria:
• Showing fever and respiratory symptoms with radiological findings of pneumonia.
• Requiring between 3L/min and 5L/min of oxygen to maintain SpO2 >97%
Severe cases (score 5; 7-point ordinal scale) i.e. cases meeting any of the following criteria:
• Respiratory distress (≧30 breaths/ min);
• Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with
O2 > 5L/min.
• PaO2/FiO2≦300mmHg
4. Male or non-pregnant female adult ≥ 18 years of age at time of enrolment.
5. Patient with body weight > 45 kg and body mass index (BMI) ≥ 18 and ≤35 kg/m2.
6. Patient must be able and willing to comply with study visits and procedures.
7. Patient agrees to the collection of nasopharyngeal swabs and venous blood per protocol
8. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures.
9. Contraception:
- Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an effective method of contraception by her male partner during treatment and for 6 months after the last treatment intake
- Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during treatment and for 3 months after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake
Highly effective and effective methods of contraception are detailed in appendix 19.3 of the protocol.
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| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
1. Recent history of severe cardiovascular disease including acute myocardial infarction, unstable angina pectoris, coronary revascularization procedure, congestive heart failure of NYHA Class III or IV, stroke, including a transient ischemic attack, edema of cardiac origin and left ventricular ejection fraction ≤ 50%, prolongation of the congenital or acquired QT interval.
2. Patient who had major surgery within 2 weeks prior to screening visit.
3. Patient with known hypersensitivity to masitinib or to any of theirs excipients
4. Patient with severe hepatic impairment defined as hepatic transaminase levels > 5 ULN or total bilirubin level > 1.5 ULN
5. Patient with severe renal impairment defined as a glomerular filtration rate < 30 ml/min/1.73 m2.
6. Patient on treatment for malignancy or with a history of cancer in the preceding 5 years, except adequately treated non-melanoma skin cancer.
7. Patient with atopic disease
8. Concomitant use of strong inducer of CYP3A4, substrate of CYP3A4 with narrow therapeutic index.
9. Concomitant treatment with CYP2C8 inhibitors
10. Patient with concomitant treatment or therapies associated with severe drug-induced skin toxicity.
11. Patient unable to swallow oral treatments
12. Pregnancy and lactation.
13. Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
• Absolute neutrophils count (ANC) ≤ 1.5 x 109/L
• Haemoglobin ≤ 10 g/dL
• Platelets (PLT) ≤ 100 x 109/L
• Albuminemia ≤ 1 x LLN
14. Patient with any condition that the physician judges could be detrimental to patient participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical conditions.
15. Patient enrolled in any other therapeutic clinical trial with the same endpoints.
16. Absence of Social Security
17. Patient protected by law under guardianship or curatorship
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| E.5 End points |
| E.5.1 | Primary end point(s) |
• Clinical status of patients at day15 using the 7-point ordinal scale.
The 7-point ordinal scale for clinical status is: 1. Not hospitalized, no limitations on activities; 2.Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
The following endpoints will be assessed at day 8 and and at the end of the study or at discharge:
• Clinical status of patients on the 7-point ordinal scale.
The following endpoints will be assessed at day 8, day 15 and at the end of the study or at discharge:
• improvement in clinical status of patients (Improvement is defined as score 1 or 2 for moderate COVID-19 patients and 1, or 2 or 3 for severe COVID-19 patients)
• Worsening in clinical status of patients (Worsening is defined as score 5 or 6 or 7 for moderate COVID-19 patients and 6 or 7 for severe COVID-19 patients)
• Time to improvement of two categories in clinical status of patients or discharge (Improvement is defined as score 1 or 2 for moderate COVID-19 patients and 1, or 2 or 3 for severe COVID-19 patients)
• Time to worsening of two categories in clinical status of patients or need of invasive intubation (Worsening is defined as score 5 or 6 or 7 for moderate COVID-19 patients and 6 or 7 for severe COVID-19 patients)
• % of patients with normal 02 saturation
• % of patients without need of oxygenation
• % of patients discharged
• % of patients requiring invasive intubation
• % of death
• % of patients negative in viral load
• Time to reach negative viral load
• CT scan or chest X-ray improvement, stable, and worsening
Safety Analysis:
• Cumulative incidence of serious adverse events (SAEs)
• Cumulative incidence of Grade 3 and 4 AEs.
• IMP Discontinuation (for any reason)
• Changes in white cell count, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, and AST over time.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Up to end of the study or at discharge |
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| 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 | No |
| 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 | 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 | No |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
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| The end of study is defined as the date of the last visit of the last patient undergoing the trial |
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| 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 |
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