POOR ACCRUAL

Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

Approximately forty-eight (48) participants will be randomized 1:1 to receive

(a) Intramuscular (IM) administration of CYT107 at 10 μg/kg followed, after 72hrs of observation, by 10 μg/kg twice a week for 3 weeks (maximum 7 administrations adjusted to patient's length of stay in the hospital) or (b) Intramuscular (IM) placebo (normal saline) at the same frequency.

The aim of the study is to test the ability of CYT107 to produce an immune reconstitution of these patients and observe possible association with a clinical improvement.

This cohort is dedicated to oncology patients

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. Patient receiving active or recent chemotherapy or immunotherapy (within 6 months) for cancer (and/or)

3. Patients who have received hematopoietic stem cell transplantation (for a diagnosis other than lymphoma) within the past 1 year (and/or)

4. Patients who received CAR-T cell therapy within the past 1 year (but not within last 30 days- see also exclusion criteria number 6 & 7) (and/or)

5. Patients receiving hormonal therapy for cancer (and/or)

6. Patients who have undergone surgery or radiotherapy for cancer within the past 6 months

7. Patients with newly diagnosed (biopsy proven) malignancy who have not yet received cancer treatment but get COVID pneumonia in the interim (Incl. Criteria 11)

8. Men and women aged ≥ 25 - 80 (included) years of age

9. Hospitalized patients with one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline .

   From this time point the investigator may choose to further postpone the commencement of IL-7 (CYT107) treatment according to patient's clinical status.

10. 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

11. Confirmed infection with COVID-19 by any acceptable test available/utilized at each site

12. Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure

Exclusion Criteria:

1. Pregnancy or breast feeding;
2. ALT and/or AST > 5 x ULN
3. Known, active auto-immune disease;
4. Patients with a history of lymphoid malignancy
5. Patients with any malignancy that is present at time of enrollment where treating physician expects life expectancy due to the underlying malignancy to be less than 6 months
6. Patients who received CAR-T cell therapy within the past 30 days or with unresolved cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS)
7. Patients with unresolved grade > 2 toxicities from prior chemotherapy, immunotherapy, or CAR-T cell therapy
8. Patients with past history of Solid Organ transplant.
9. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load.
10. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours
11. Patients with a mechanical ventilation support ≥ 7 days
12. Patients with chronic kidney dialysis
13. Patients with a SOFA score ≥ 9 at baseline
14. Patients with a BMI > 40
15. Patients showing an increase of the NEWS2 score by more than 6 points during the screening/ baseline period (48 to 72 hrs prior to first administration)
16. Patients with hospital admission Rockwood Clinical Frailty Scale ≥ 6. (assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection)

11. Patients under guardianship

Publication

Unblinded Pharmacist will prepare blinded syringes of colorless drug or placebo