E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.3 | 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 of the study is to improve the absolute lymphocyte count (ALC) of lymphopenic (ALC≤700/mm3) COVID-19 infected participants out to 30 days or Hospital discharge (HD), whichever comes first. |
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E.2.2 | Secondary objectives of the trial |
-Obtain “clinical improvement” as defined by a 2 points improvement in a 7-point ordinal scale, through D30 or HD -determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through D30 or HD -Compare: incidence of grade 3-4 AE for CYT107 vs placebo through D45 Effect of CYT107 vs placebo on the frequency of secondary infections through D45, on the length of hospitalization, on the length of stay in ICU, on readmissions to ICU, on organ support free days through day 30 or HD following initial drug administration, on the frequency of re-hospitalization through D45 -Assess the impact of CYT107 on all-cause mortality through D45 -Determine the effect of CYT107 on T cell counts (CD4+,CD8+) through day 30 or HD -Track and evaluate other biomarkers: of immune function: monocyte HLA-DR expression and of inflammation: CRP, D-dimer, Ferritin -Evaluation of physiological status through NEWS2 score |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A written, signed informed consent, or emergency oral consent by the patient or the patient’s legally authorized representative, and the anticipated ability for participant to be re-consented in the future for ongoing Study participation 2. Men and women aged ≥ 25 – 80 (included) years of age 3. Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 700 cells/mm3, at two time points at least 24 hours apart, following HOSPITALIZATION: The FIRST time point should not be performed earlier than 48 hours after Hospitalization, thus first test dose can’t be administered before 72 hours after hospitalization (From this time point the investigator may choose to further postpone the commencement of IL-7 (CYT107) treatment according to patient’s clinical status) 4. Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at >4L per minute nasal cannula or greater to keep saturations >90%, non-invasive positive pressure ventilation (e.g., BIPAP), or patients intubated/ventilated for respiratory failure 5. Confirmed infection with COVID-19 by any acceptable test available/utilized at each site 6. Patient with medical insurance or government support
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E.4 | Principal exclusion criteria |
1. Pregnancy or breast feeding; 2. Refusal or inability to practice contraception regardless of the gender of the patient; 3. ALT and/or AST > 5 x ULN 4. Known, active auto-immune disease; 5. Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing; 6. Patients with past history of Solid Organ transplant. 7. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load. 8. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours 9. Patients receiving any agent with immune suppressive effects, other than steroids at dosages less than 300mg/day and/or anti-IL6 treatments like Tocilizumab or Sarilumab which should preferably be minimized 10. Patients with baseline Rockwood Clinical Frailty Scale ≥ 6. 11. Patients under guardianship
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E.5 End points |
E.5.1 | Primary end point(s) |
An improvement in the absolute lymphocyte count (ALC) is defined as a statistically significant increase from randomization to day 30 or HD, and will also be assessed at defined timepoints (as indicated in the Schedule of Activities, to include all Study drug administration days). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
days 0, 1, 5 or 6, 14, 21 and 30 or hospital discharge |
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E.5.2 | Secondary end point(s) |
a) The time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale, or live discharge from the hospital (HD), whichever comes first. This clinical outcome will be assessed at defined timepoints (indicated in the Schedule of Activities). The time course of the seven points score improvement will be compared between the CYT107 group and the placebo group. b) The decrease of SARS-Co-V-2 viral load from measurements. Viral load is measured from nasal swab or endotracheal secretions. The time course of the viral load drop will be compared between the CYT107 group and the placebo group . c) Incidence and scoring of all grade 3-4 adverse events (using CTCAE Version 5.0 to assess severity) d) Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) e) Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through hospital discharge) f) Number of days in ICU during index hospitalization (Index hospitalization is defined as date and time of first drug treatment through hospital discharge.) g) Incidence of re-admission to ICU h) Number of organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days) i) Number of readmissions to the hospital j) All-cause mortality k) Absolute numbers of CD4+ and CD8+ T-cell counts l) Examination and evaluation of effect of CYT107 on immune biomarkers: monocyte HLA-DR expression m) Track and evaluate other known biomarkers of inflammation, CRP, D-dimer, and Ferritin, at SoA timepoints n) Evaluate improvement of the NEWS2 score value
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) through day 30 or HD b) at baseline to days between day 9 to day 11, between day 12 to day 18, 21 and day 30 or HD (whichever first) c) through day 45 d) through day 45 e) HD f) HD g) through D45 h) HD i) through D45 j) through D45 k) at baseline, days 3, between day 9 to day 11, between day 12 to day 18, 30 or HD l) at baseline, between day 9 to day 11 and day 30 or HD for HLA-DR m) at baseline, days 1, 3, 7 or 8, between day 9 to day 11, between day 12 to day 18, 30 or HD n) at baseline, days 1, 3, 7 or 8, between day 9 to day 11, between day 12 to day 18, 21 and 30 or HD |
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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 | Yes |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
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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 last visit of the last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 5 |