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

Study Overview
=================
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 7administrations 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 excludes oncology patients on treatment

Official Title
-----------------
A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Infectious Cohort

Conditions
-----------------
COVID-19, Lymphocytopenia

Intervention / Treatment
-----------------
* Drug: CYT107
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Men and women aged ≥ 25 - 80 (included) years of age Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, at two time points at least 24 hours apart, following HOSPITALIZATION: 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 Confirmed infection with COVID-19 by any acceptable test available / utilized at each site Willingness and ability to practice contraception regardless of the gender of the patient during 5 month after last drug exposure Private insurance or government / institution financial support (through CMS or other) Exclusion Criteria: Pregnancy or breast feeding ALT and/or AST > 5 x ULN Known, active auto-immune disease; Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing Patients with past history of Solid Organ transplant Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours Patients receiving any agent with immune suppressive effects, other than steroids at dosages less than 300 mg/day equivalent hydrocortisone and/or anti-IL-6R treatments like Tocilizumab or Sarilumab or anti-IL-1 treatment like Anakinra which should preferably be minimized Patients with baseline Rockwood Clinical Frailty Scale ≥ 6 at Hospital admission 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) Patients under guardianship

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized controlled of treatment vs placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYT107 Treatment<br>Intramuscular (IM) administration of CYT107 twice a week for 3 weeks | Drug: CYT107<br>* IM administration at 10μg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay<br>* Other names: Interleukin-7;|
| Placebo Comparator: Placebo<br>Intramuscular (IM) administration of Saline twice a week for 3 weeks | Drug: Placebo<br>* IM administration at 10μg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay<br>* Other names: Saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 first | A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To obtain clinical improvement as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD. | to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by 11 steps WHO clinical improvement score | one month | 
| a significant decline of SARS-CoV-2 viral load through day 30 or HD | 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) | one month | 
| frequency of secondary infections through day 45 compared to placebo arm | Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45 | 45 days | 
| length of hospitalization compared to placebo arm | Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD) | 45 days | 
| Length of stay in ICU compared to placebo arm | Number of days in ICU during index hospitalization | 45 days | 
| number of readmissions to ICU compared to placebo arm | Readmissions to ICU through Day 45 | 45 days | 
| organ support free days compared to placebo arm | Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days) | 45 days | 
| Frequency of re-hospitalization through day 45 compared to placebo arm | Number of readmissions to the hospital through Day 45 | 45 days | 
| All-cause mortality through day 45 compared to placebo arm | All-cause mortality through Day 45 | 45 days | 
| CD4+ and CD8+ T cell counts compared to placebo arm | Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD | 30 days | 
| level of other known biomarkers of inflammation: Ferritin compared to placebo a | Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30 | 30 days | 
| Level of other known biomarkers of inflammation: CRP compared to placebo arm | Level of other known biomarkers of inflammation: CRP compared to placebo arm | 30 days | 
| Level of other known biomarkers of inflammation: D-dimer compared to placebo arm | Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30 | 30 days | 
| Physiological status through NEWS2 evaluation compared to Placebo arm | Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk | 30 days |