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InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic Patients With COVID-19 Infection ( ILIAD-7-US-O )

Phase 2
Terminated
Conditions
Lymphocytopenia
COVID-19
Interventions
Drug: Placebo
Registration Number
NCT04426201
Lead Sponsor
Revimmune
Brief Summary

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

Detailed Description

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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
10
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)

  17. Patients under guardianship

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CYT107 TreatmentCYT107Intramuscular (IM) administration of CYT107 twice a week for 3 weeks
Saline controlPlaceboIntramuscular (IM) placebo (normal saline) at the same frequency
Primary Outcome Measures
NameTimeMethod
Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs firstone month

A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or HospitalDischarge

Secondary Outcome Measures
NameTimeMethod
Physiological status through NEWS2 evaluation compared to Placebo arm30 days

Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

frequency of secondary infections through day 45 compared to placebo arm45 days

Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

a significant decline of SARS-CoV-2 viral load through day 30 or HD1 month or HD (whichever occurs first)

The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

length of stay in ICU compared to placebo arm45 days

Number of days in ICU during index hospitalization

number of readmissions to ICU compared to placebo arm45 days

Readmissions to ICU through Day 45

To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.one month

to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by 11 steps WHO clinical improvement score

organ support free days compared to placebo arm45 days

Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

level of other known biomarkers of inflammation: Ferritin compared to placebo arm30 days

Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

length of hospitalization compared to placebo arm45 days

Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

CD4+ and CD8+ T cell counts compared to placebo arm30 days

Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA) through Day 30 or HD

Frequency of re-hospitalization through day 45 compared to placebo arm45 days

Number of readmissions to the hospital through Day 45

All-cause mortality through day 45 compared to placebo arm45 days

All-cause mortality through Day 45

Level of other known biomarkers of inflammation: CRP compared to placebo arm30 days

Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30

Level of other known biomarkers of inflammation: D-dimer compared to placebo arm30 days

Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

Trial Locations

Locations (2)

MD Anderson cancer center

🇺🇸

Houston, Texas, United States

Memorial sloan kettering

🇺🇸

New York, New York, United States

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