InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort

Study Overview
=================
Brief Summary
-----------------
Comparison of the effects of CYT107 vs Placebo administered IM at 10µg/kg twice a week for two 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 3 μg/kg followed, after 48hrs of observation, by 10 μg/kg twice a week for 2 weeks or (b) Intramuscular (IM) placebo (normal saline) at the same frequency. An interim safety review will take place after the first 12 patients. If the CYT107 is well tolerated, the test dose (3 μg/kg) will cease and that initial dose will become the same as the rest of the doses (10 μg/kg). So, the remaining patients will be randomized to receive 5 administrations of (a) CYT107 at 10 μg/kg every 3 to 4 days for 2 weeks 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

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 in UK

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

Intervention / Treatment
-----------------
* Drug: Interleukin-7
* Drug: Placebos


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 one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at >2L 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 Private insurance or government support (through NHS or other) Exclusion Criteria: Pregnancy or breast feeding; Refusal or inability to practice contraception regardless of the gender of the patient; 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. Patients whose respiratory condition is showing significant deterioration as indicated by: requirement for a persistent and sustained increase in inspired oxygen concentrations of 20% or more over the past 24 hours to maintain SpO2 at greater than or equal to 88% (this 20 % limit does not apply to O2 delivered by nasal canula) or need for invasive mechanical ventilation Patients with chronic kidney dialysis 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 with a SOFA score ≥ 9 at baseline Patients with a BMI > 40 Patients with baseline Rockwood Clinical Frailty Scale ≥ 6.(assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection) 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<br>Intra-muscular administration of CYT107 twice a week for a total of 5 administrations | Drug: Interleukin-7<br>* Intramuscular (IM) administration of CYT107 at 3 μg/kg followed, after 48hrs of observation, by 10 μg/kg twice a week for 2 weeks or<br>* Other names: CYT107;|
| Placebo Comparator: Saline<br>Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations | Drug: Placebos<br>* Intramuscular (IM) placebo (normal saline) at the same frequency<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), whicheve | A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge | 1 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 WHO score | 1 month | 
| determine if CYT107 will lead to 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 | 
| To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45 | Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45 | 45 days | 
| To compare the effect of CYT107 versus placebo on the length of hospitalization | Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD) | 45 days | 
| To compare the effect of CYT107 versus placebo on the length of stay in ICU | Number of days in ICU during index hospitalization | 45 days | 
| To compare the effect of CYT107 versus placebo on readmissions to ICU | Readmissions to ICU through Day 45 | 45 days | 
| To compare the effect of CYT107 versus placebo on organ support free days | Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.) | 45 days | 
| To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45 | Number of readmissions to the hospital through Day 45 | 45 days | 
| To assess the impact of CYT107 on all-cause mortality through day 45 | All-cause mortality through Day 45 | 45 days | 
| To determine the effect of CYT107 on CD4+ and CD8+ T cell counts | Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD | 30 days | 
| To track and evaluate other known biomarkers of inflammation: Ferritin | Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30 | 30 days | 
| To track and evaluate other known biomarkers of inflammation: CRP | Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30 | 30 days | 
| To track and evaluate other known biomarkers of inflammation: D-dimer | Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30 | 30 days | 
| Evaluation of physiological status through NEWS2 score | Evaluate improvement of the NEWS2 score value | 30 days |