Clinical trial NCT04379076: InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Lymphocytopenia
Lead sponsor: Revimmune
Sponsor class: INDUSTRY
Collaborators: name: Amarex Clinical Research
First posted: 2020-05-07
Enrollment: 35
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled of treatment vs placebo
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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
timeFrame: 1 month
Secondary outcomes:
measure: To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.
timeFrame: 1 month
measure: determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD
timeFrame: one month
measure: To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45
timeFrame: 45 days
measure: To compare the effect of CYT107 versus placebo on the length of hospitalization
timeFrame: 45 days
measure: To compare the effect of CYT107 versus placebo on the length of stay in ICU
timeFrame: 45 days
measure: To compare the effect of CYT107 versus placebo on readmissions to ICU
timeFrame: 45 days
measure: To compare the effect of CYT107 versus placebo on organ support free days
timeFrame: 45 days
measure: To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45
timeFrame: 45 days
measure: To assess the impact of CYT107 on all-cause mortality through day 45
timeFrame: 45 days
measure: To determine the effect of CYT107 on CD4+ and CD8+ T cell counts
timeFrame: 30 days
measure: To track and evaluate other known biomarkers of inflammation: Ferritin
timeFrame: 30 days
measure: To track and evaluate other known biomarkers of inflammation: CRP
timeFrame: 30 days
measure: To track and evaluate other known biomarkers of inflammation: D-dimer
timeFrame: 30 days
measure: Evaluation of physiological status through NEWS2 score
timeFrame: 30 days
Other outcomes:
measure: Safety assessment
timeFrame: 45 days
Locations:
city: Birmingham
country: United Kingdom
facility: Sandwell Birmingham Hospital
city: Birmingham
country: United Kingdom
facility: Sandwell Birmingham Hospital
city: Bradford
country: United Kingdom
facility: Bradford Institute for Health Research
city: Leeds
country: United Kingdom
facility: ST JAMES's UNIVERSITY HOSPITAL
city: London
country: United Kingdom
facility: Medway Maritime Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King'S College Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital/ Manchester Royal Infirmary
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary and Freeman Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
city: Watford
country: United Kingdom
facility: Watford General Hospital
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Manu Shankar-Hari, MD PhD
role: PRINCIPAL_INVESTIGATOR
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